INREBIC provides new, once-daily oral option for patients affectedby rare bone marrow cancer

MONTREAL, Sept. 21, 2020 /CNW/ - Bristol Myers Squibb Canada (BMS) announced today that Health Canada has approved INREBIC (fedratinib), a new once-daily oral medication used to treat adults with an enlarged spleen and associated symptoms caused by intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.1

INREBICis the first new treatment for patients with myelofibrosis in nearly a decade to demonstrate a clinically meaningful reduction in spleen volume for patients in the approved population affected by this serious and rare bone marrow cancer.1 A new treatment provides Canadians living with myelofibrosis, and their caregivers, with more options to find a treatment that works for them.

Myelofibrosis is a serious and rare bone marrow disorder that disrupts the body's normal production of blood cells.2 Bone marrow is gradually replaced with fibrous scar tissue, which limits the ability of the bone marrow to make blood cells.2 Currently, there are an estimated 1,400 to 2,177 Canadians who are living with myelofibrosis.3

"The approval of INREBIC represents a milestone for the way healthcare practitioners treat this rare disorder, which can have debilitating symptoms," said Dr. Vikas Gupta, Director, The Elizabeth and Tony Comper MPN Program, Princess Margaret Cancer Centre, Toronto. "Canadians living with myelofibrosis now have a new treatment option that may be better suited to their needs and has shown promise for alleviating the symptom burden associated with myelofibrosis."

INREBIC is a janus kinase (JAK) inhibitor and is the first new treatment for patients with myelofibrosis in nearly a decade.1,4 JAK proteins send signals that tell the body to make more blood cells, but myelofibrosis makes it difficult for the bone marrow to create normal blood cells, which potentially moves blood cell production to the spleen.1 However, by blocking the activity of JAK proteins, INREBIC can reduce the size of the spleen and improve symptoms.

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"As part of our commitment to Canadians living with cancer, we are excited to provide INREBIC as a new treatment option for those impacted by myelofibrosis," said Al Reba, General Manager, Bristol Myers Squibb Canada. "We hope that the option of a once-daily oral treatment will have a positive and meaningful impact on Canadians living with the disease."

Health Canada's approval of INREBIC included findings from the JAKARTA and JAKARTA2 clinical trials. The JAKARTA study, a double-blind, randomized, placebo-controlled Phase 3 study, involved patients with intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. The JAKARTA2 study, a multicenter, open-label, single-arm Phase 2 study,involved patients previously exposed to ruxolitinib with a diagnosis of intermediate-1 with symptoms, intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.

About MyelofibrosisMyelofibrosis is classified as a myeloproliferative neoplasm, a group of rare blood cancers that are derived from blood-forming stem cells.2Myelofibrosis can lead to anemia and thrombocytopenia, weakness, fatigue and enlargement of the spleen and liver, among other symptoms.2 In Canada, approximately 36 to 360 people will be diagnosed with myelofibrosis each year.3 Both men and women are affected, and while the disease can affect people of all ages, the median age at diagnosis is 69 years old.3

About JAKARTAJAKARTA was a double-blind, randomized, placebo-controlled Phase 3 study in patients with intermediate-2 or high-risk myelofibrosis (MF), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis with splenomegaly and platelet count 50 x 109/L. A total of 289 patients were randomized to receive either INREBIC 500 mg (N=97), 400 mg (N=96), or placebo (N=96) once daily for at least 6 cycles. The median age was 65 years (range 27 to 86 years), 47% of patients were older than 65 years, and 59% were male. Sixty-four percent (64%) of patients had primary MF, 26% had post-polycythemia vera MF, and 10% had post-essential thrombocythemia MF. Fifty-two percent (52%) of patients had intermediate-2 risk, and 48% had high-risk disease. The median hemoglobin count at baseline was 10.2 g/dL. The median platelet count at baseline was 213.5 x 109/L; 16.3% of patients had a platelet count <100 x 109/L, and 83.7% of patients had a platelet count 100 x 109/L. Patients had a median palpable spleen length of 15 cm at baseline and a median spleen volume as measured by magnetic resonance imaging (MRI) or computed tomography (CT) of 2568 mL (range of 316 to 8244 mL) at baseline. (The median normal spleen volume is approximately 215 mL).1

The primary efficacy endpoint was the proportion of patients achieving a greater than or equal to 35% reduction from baseline in spleen volume at the End of Cycle 6 as measured by MRI or CT and confirmed 4 weeks later.1

One of the secondary endpoints was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to the End of Cycle 6 as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) v2.0 diary.1

About JAKARTA2JAKARTA2 was a multicenter, open-label, single-arm Phase 2 study in patients previously exposed to ruxolitinib with a diagnosis of intermediate-1 with symptoms, intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis with splenomegaly and platelet count 50 x 109/L.1

A total of 97 patients were enrolled and treated with INREBIC400 mg once daily. The median age was 67 years (range 38 to 83 years) with 58% of patients older than 65 years and 55% were male. Fifty-five percent (55%) of patients had primary MF, 26% had post-polycythemia vera MF, and 19% had post-essential thrombocythemia MF. Sixteen percent (16%) of patients had intermediate-1 with symptoms, 49% had intermediate-2, and 35% had high-risk disease. The median hemoglobin count was 9.8 g/dL at baseline. The median platelet count was 147.0 x 109/L at baseline; 34.0% of patients had a platelet count <100 x 109/L, and 66.0% of patients had a platelet count 100 x 109/L. Patients had a median palpable spleen length of 18 cm at baseline and a median spleen volume as measured by magnetic resonance imaging (MRI) or computed tomography (CT) of 2893.5 mL (range of 737 to 7815 mL) at baseline.1

The median duration of prior exposure to ruxolitinib was 10.7 months (range 0.1 to 62.4 months). Seventy-one percent (71%) of patients had received doses of either 30 mg or 40 mg daily of ruxolitinib prior to study entry.1

The primary endpoint was the subject response rate, defined as the proportion of subjects who have a 35% reduction in volume of spleen size at the end of Cycle 6.1

One of the secondary endpoints was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to the End of Cycle 6 as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) diary.1

About INREBICINREBIC (fedratinib) is indicated for the treatment of splenomegaly and/or disease related symptoms in adult patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis, including patients who have been previously exposed to ruxolitinib.

About Bristol Myers Squibb Canada

Bristol Myers Squibb Canada Co. is an indirect wholly-owned subsidiary of Bristol Myers Squibb Company, a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb global operations, visitwww.bms.com. Bristol Myers Squibb Canada Co. delivers innovative medicines for serious diseases to Canadian patients in the areas of cardiovascular health, oncology, and immunoscience. Bristol Myers Squibb Canada Co. employs more than 300 people across the country. For more information, please visitwww.bmscanada.ca.

About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us atBMS.comor follow us on LinkedIn, Twitter, YouTube, Facebookand Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

References:

INREBICCanada Product Monograph. July 10, 2010.

Leukemia & Lymphoma Society of Canada. Myelofibrosis. Available at: https://www.llscanada.org/myeloproliferative-neoplasms/myelofibrosis. Accessed July 28, 2020.

Corinne S. Hodgson & Associates. Blood Cancer in Canada Facts & Stats 2016. Leukemia & Lymphoma Society of Canada 2016; 4-8.

Canadian MPN Group. Myelofibrosis. Available at: http://www.mpncanada.com/about-mpns/practitioner-reference/myelofibrosis/#treatment-options. Accessed July 28, 2020.

SOURCE Bristol Myers Squibb Canada Co.

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Health Canada Approves INREBIC (fedratinib), First New Treatment in Nearly a Decade for Patients Living with Myelofibrosis - Yahoo Finance

Bone Marrow Stem Cells Comments Off on Health Canada Approves INREBIC (fedratinib), First New Treatment in Nearly a Decade for Patients Living with Myelofibrosis – Yahoo Finance | September 22nd, 2020

Since late June, life has changed for Rylee Schroeder and her parents, Megan and Levi Schroeder.

It was then the Neosho High School senior sought help for extreme fatigue, shortness of breath, nosebleeds and more. The symptoms, combined with a previously diagnosed issue with low platelets, led Rylees pediatrician to run a series of lab tests.

The news sent the family first to Freeman Hospital West in Joplin, and then Childrens Mercy Hospital in Kansas City.

Doctors discovered Rylees low hemoglobin, platelets and white blood counts were caused by myelodysplastic syndrome. Additional testing revealed the teen has an extremely rare congenital disorder called Shwachman-Diamond syndrome and a TP53 gene mutation that led to the MDS.

Megan said her daughter is only the 36th patient known to have this combination of illnesses, which have progressed to bone marrow failure.

On Friday, Rylee received a stem cell bone marrow transplant at Childrens Mercy in Kansas City, thanks to a donation from her 12-year-old brother Colin.

Megan said her son was a 12/12 match for Rylee. Typically, doctors look for a 10/10 match, or a 5/5 match with a parent. The Be a Match Donor Registry located four 10/10 matches, two donors in the United States and two international donors.

If everything goes well with the transplant, doctors hope to see Colins stem cells begin to take hold in Rylees body between Day 14 to Day 21, post transplant.

Relying on faith

Through everything, Rylee and her family are relying on their faith, as well as support from friends at Racine Christian Church and within the community of Neosho, to get them through the tough days.

We are lucky to have a great church and thankful Sunday serves are online on Facebook, Megan said. We may not be there, but we still feel a part of it, and they are always ready to lift us up.

Many times, Ive thought Im not strong enough to do this, but Im reminded that I am. We are so tired and weary but (God) has us.

Megan said shes used to being the one to offer help through giving and volunteering. Now their family is on the other side, leaning on the support of others.

Our faith means everything to us, Megan said. Without it, we wouldnt be doing as well as we are. Its hard enough as it is. If you dont have something to believe in with your whole heart to guide you and lean on, you would just be lost. It would be overwhelming to take it on yourself.

More about Rylee

Rylee, who turned 17 shortly after her diagnosis, is active in the NHS show choir, choir, Key Club and FCA.

A member of the Racine Christian Church youth leadership team, she was also slated to go to Ireland this summer pre-pandemic with the churchs mission team.

This past Thursday, Rylee was highlighted at the NHS volleyball game for childhood cancer awareness month. On Friday, she was recognized at the home football game.

Members of her show choir helped start a Go Fund Me account earlier this summer to help the family with travel expenses to and from Kansas City. Her youth minister has since created another one to help with the coming months.

Megan said the family always helps at Solomons Dance Studio recitals because the owner, Charity, uses the lessons to teach children to love dance and to love others as well as themselves.

Rylee was able to to attend the recital to watch her sister Erin dance. On the last day of the recital, Charity asked the entire family to come forward, offering prayers over the entire situation.

Rylees small group from the church, which meets on Wednesday evenings, livechats with her, allowing the teen to continue to be part of the discussions.

Before Rylee was admitted to begin the chemo needed prior to the transplant, she asked to rededicate her life to Christ. Megan said she wanted to feel his strength renewed as she went into the fight.

Our close friends all stayed behind after church that Sunday, even though it was last minute, to be witness to her baptism, Megan said. They are some of our strongest supporters. We would be lost without them.

Megan said those friends, steeped in faith, give her strength to sit at the hospital, holding Rylees hand.

I can reach out to any of them to start praying with me to help make me feel stronger when I feel I am failing her, Megan said. I know Gods got this. He is strong all the time even when we can not be strong.

Biblical baubles

Many of Rylee Schroeders friends are wearing a Rally behind Rylee bracelet featuring Isaiah 41:10: So do not fear, for I am with you; do not be dismayed, for I am your God. I will strengthen you and help you; I will uphold you with my righteous right hand.

A family friend made them to distribute to members of the community. A limited number remain. Information about the bracelets, and Rylees journey, may be found on a Facebook page, Rally Behind Rylee.

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Faith for the fight: Neosho teen deals with rare combination of illnesses - Joplin Globe

Bone Marrow Stem Cells Comments Off on Faith for the fight: Neosho teen deals with rare combination of illnesses – Joplin Globe | September 21st, 2020

INREBIC provides new, once-daily oral option for patients affected by rare bone marrow cancer

MONTREAL, Sept. 21, 2020 /CNW/ - Bristol Myers Squibb Canada (BMS) announced today that Health Canada has approved INREBIC (fedratinib), a new once-daily oral medication used to treat adults with an enlarged spleen and associated symptoms caused by intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.1

INREBIC is the first new treatment for patients with myelofibrosis in nearly a decade to demonstrate a clinically meaningful reduction in spleen volume for patients in the approved population affected by this serious and rare bone marrow cancer.1 A new treatment provides Canadians living with myelofibrosis, and their caregivers, with more options to find a treatment that works for them.

Myelofibrosis is a serious and rare bone marrow disorder that disrupts the body's normal production of blood cells.2 Bone marrow is gradually replaced with fibrous scar tissue, which limits the ability of the bone marrow to make blood cells.2 Currently, there are an estimated 1,400 to 2,177 Canadians who are living with myelofibrosis.3

"The approval of INREBIC represents a milestone for the way healthcare practitioners treat this rare disorder, which can have debilitating symptoms," said Dr. Vikas Gupta, Director, The Elizabeth and Tony Comper MPN Program, Princess Margaret Cancer Centre, Toronto. "Canadians living with myelofibrosis now have a new treatment option that may be better suited to their needs and has shown promise for alleviating the symptom burden associated with myelofibrosis."

INREBIC is a janus kinase (JAK) inhibitor and is the first new treatment for patients with myelofibrosis in nearly a decade.1,4 JAK proteins send signals that tell the body to make more blood cells, but myelofibrosis makes it difficult for the bone marrow to create normal blood cells, which potentially moves blood cell production to the spleen.1 However, by blocking the activity of JAK proteins, INREBIC can reduce the size of the spleen and improve symptoms.

"As part of our commitment to Canadians living with cancer, we are excited to provide INREBIC as a new treatment option for those impacted by myelofibrosis," said Al Reba, General Manager, Bristol Myers Squibb Canada. "We hope that the option of a once-daily oral treatment will have a positive and meaningful impact on Canadians living with the disease."

Health Canada's approval of INREBIC included findings from the JAKARTA and JAKARTA2 clinical trials. The JAKARTA study, a double-blind, randomized, placebo-controlled Phase 3 study, involved patients with intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. The JAKARTA2 study, a multicenter, open-label, single-arm Phase 2 study, involved patients previously exposed to ruxolitinib with a diagnosis of intermediate-1 with symptoms, intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.

About MyelofibrosisMyelofibrosis is classified as a myeloproliferative neoplasm, a group of rare blood cancers that are derived from blood-forming stem cells.2 Myelofibrosis can lead to anemia and thrombocytopenia, weakness, fatigue and enlargement of the spleen and liver, among other symptoms.2 In Canada, approximately 36 to 360 people will be diagnosed with myelofibrosis each year.3 Both men and women are affected, and while the disease can affect people of all ages, the median age at diagnosis is 69 years old.3

About JAKARTAJAKARTA was a double-blind, randomized, placebo-controlled Phase 3 study in patients with intermediate-2 or high-risk myelofibrosis (MF), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis with splenomegaly and platelet count 50 x 109/L. A total of 289 patients were randomized to receive either INREBIC 500 mg (N=97), 400 mg (N=96), or placebo (N=96) once daily for at least 6 cycles. The median age was 65 years (range 27 to 86 years), 47% of patients were older than 65 years, and 59% were male. Sixty-four percent (64%) of patients had primary MF, 26% had post-polycythemia vera MF, and 10% had post-essential thrombocythemia MF. Fifty-two percent (52%) of patients had intermediate-2 risk, and 48% had high-risk disease. The median hemoglobin count at baseline was 10.2 g/dL. The median platelet count at baseline was 213.5 x 109/L; 16.3% of patients had a platelet count <100 x 109/L, and 83.7% of patients had a platelet count 100 x 109/L. Patients had a median palpable spleen length of 15 cm at baseline and a median spleen volume as measured by magnetic resonance imaging (MRI) or computed tomography (CT) of 2568 mL (range of 316 to 8244 mL) at baseline. (The median normal spleen volume is approximately 215 mL).1

The primary efficacy endpoint was the proportion of patients achieving a greater than or equal to 35% reduction from baseline in spleen volume at the End of Cycle 6 as measured by MRI or CT and confirmed 4 weeks later.1

One of the secondary endpoints was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to the End of Cycle 6 as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) v2.0 diary.1

About JAKARTA2JAKARTA2 was a multicenter, open-label, single-arm Phase 2 study in patients previously exposed to ruxolitinib with a diagnosis of intermediate-1 with symptoms, intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis with splenomegaly and platelet count 50 x 109/L.1

A total of 97 patients were enrolled and treated with INREBIC 400 mg once daily. The median age was 67 years (range 38 to 83 years) with 58% of patients older than 65 years and 55% were male. Fifty-five percent (55%) of patients had primary MF, 26% had post-polycythemia vera MF, and 19% had post-essential thrombocythemia MF. Sixteen percent (16%) of patients had intermediate-1 with symptoms, 49% had intermediate-2, and 35% had high-risk disease. The median hemoglobin count was 9.8 g/dL at baseline. The median platelet count was 147.0 x 109/L at baseline; 34.0% of patients had a platelet count <100 x 109/L, and 66.0% of patients had a platelet count 100 x 109/L. Patients had a median palpable spleen length of 18 cm at baseline and a median spleen volume as measured by magnetic resonance imaging (MRI) or computed tomography (CT) of 2893.5 mL (range of 737 to 7815 mL) at baseline.1

The median duration of prior exposure to ruxolitinib was 10.7 months (range 0.1 to 62.4 months). Seventy-one percent (71%) of patients had received doses of either 30 mg or 40 mg daily of ruxolitinib prior to study entry.1

The primary endpoint was the subject response rate, defined as the proportion of subjects who have a 35% reduction in volume of spleen size at the end of Cycle 6.1

One of the secondary endpoints was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to the End of Cycle 6 as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) diary.1

About INREBICINREBIC (fedratinib) is indicated for the treatment of splenomegaly and/or disease related symptoms in adult patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis, including patients who have been previously exposed to ruxolitinib.

About Bristol Myers Squibb Canada

Bristol Myers Squibb Canada Co. is an indirect wholly-owned subsidiary of Bristol Myers Squibb Company, a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb global operations, visit http://www.bms.com. Bristol Myers Squibb Canada Co. delivers innovative medicines for serious diseases to Canadian patients in the areas of cardiovascular health, oncology, and immunoscience. Bristol Myers Squibb Canada Co. employs more than 300 people across the country. For more information, please visit http://www.bmscanada.ca.

About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

References:

SOURCE Bristol Myers Squibb Canada Co.

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Health Canada Approves INREBIC (fedratinib), First New Treatment in Nearly a Decade for Patients Living with Myelofibrosis - BioSpace

Bone Marrow Stem Cells Comments Off on Health Canada Approves INREBIC (fedratinib), First New Treatment in Nearly a Decade for Patients Living with Myelofibrosis – BioSpace | September 21st, 2020

Immunotherapies that are currently being studied in multiple myeloma are discussed in this section under four headings: checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody drug conjugates (fig 2).

Malignant plasma cells in most patients with multiple myeloma express the checkpoint programmed death-ligand 1, which is upregulated especially when exposed to inflammatory mediators such as interferon . Interaction of this checkpoint molecule with programmed cell death protein 1 on T cells limits their proliferation and cytotoxic activity.6869

The first study evaluating single agent nivolumab for relapsed multiple myeloma showed a response in only one of 27 patients.7071 Despite a lack of single agent activity, single arm trials combining checkpoint inhibitors with immunomodulatory imide drugs and dexamethasone because of the potential synergy72 look promising.7374

With these clinical data, three large randomized phase III trials were halted by the FDA in 2017 because of increased serious adverse events and deaths as well as decreased overall survival in the checkpoint inhibitor arm (pomalidomide and dexamethasone with and without pembrolizumab) in relapsed and refractory multiple myeloma (hazard ratio 1.61, 95% confidence interval 0.91 to 2.85),75 pomalidomide and dexamethasone with and without nivolumab in relapsed and refractory multiple myeloma (1.19, 0.64 to 2.20),76 and lenalidomide and dexamethasone with and without pembrolizumab in transplant ineligible patients with newly diagnosed multiple myeloma (2.06, 0.93 to 4.55)77).

These trials encourage caution with expedited timelines for future combination studies for drugs with limited single agent activity.7879 Future trials in multiple myeloma will need to be based on sound preclinical and clinical rationale with other partners and be conducted in heavily treated patients (with limited standard options) initially.

CAR T cells are human T cells that have been genetically modified and expanded in the laboratory before they are infused back into patients to target the tumor. The receptor on the surface of CAR T cells that targets the tumor antigens consists of several parts (fig 3): an extracellular, non-major histocompatibility complex restricted, targeting domain, usually derived from a single chain variable fragment of a monoclonal antibody; a spacer region; a transmembrane domain; an intracellular signaling domain including the CD3 activation domain; and a costimulatory domain (eg, CD28 or 4-1BB). The single chain variable fragment was originally derived from mice (hence the term chimeric), but many of the newer constructs are fully human.8081

Chimeric antigen receptor (CAR) T cell structure

CD3 positive T cells are obtained from patients (for autologous CAR T cells) or healthy donors (for allogeneic CAR T cells) via a process called leukapheresis. These T cells are expanded manifold in culture and activated using beads coated with anti-CD3 or anti-CD28 monoclonal antibodies or cell based artificial antigen presenting cells.82 The T cells are then transduced with a vector (usually either lentiviral or retroviral) that carries the gene encoding a receptor to an antigen present on the surface of tumor cells. This manufacturing process takes up to four weeks at a good manufacturing practices facility, and the CAR T cells can then be stored until needed by the patient. This delay means that the disease must not be rapidly progressing, so that the patient is able to wait until the CAR T product is ready; otherwise the patient will need bridging chemotherapy. Two to seven days before CAR T cell infusion, a patient receives lymphodepleting chemotherapy to make way for the CAR T cells that are subsequently given as an intravenous infusion. Once infused into patients, the CAR T cells encounter the antigen, proliferate, and kill the tumor cells (fig 4). These cells, therefore, combine the target specificity of a monoclonal antibody with the enhanced cytotoxicity of T cells without requiring human leucocyte antigen presentation of the target antigen.83

Chimeric antigen receptor (CAR) T cell treatment for multiple myelomasequence of events. CRS=cytokine release syndrome; ICANS=immune effector cell associated neurotoxicity syndrome

An ideal antigen is one that is widely and exclusively expressed on cancer cells but not on normal cells to enhance efficacy and reduce toxicity.8485 In multiple myeloma, most emerging immunotherapies (including CAR T cells) target B cell maturation antigen (BCMA), a type III transmembrane receptor, which is a promising target antigen.8687 BCMA is also known as tumor necrosis factor receptor superfamily member 17 or CD269. It is expressed in nearly all plasma cells (normal and malignant) although its expression is variable.88 BCMA promotes plasma cell survival and is induced during plasma cell differentiation89 by binding to ligands (a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF)) that are produced by osteoclasts.90 Increased levels of soluble BCMA are associated with high tumor burden in multiple myeloma and thus worse outcomes.91

CAR T cells targeting CD19 were approved by the FDA in 2017 for refractory large B cell lymphoma9293 and acute lymphoblastic leukemia,94 and are being used in clinical practice. The first study on CAR T cell treatment directed by BCMA opened in 2014 at the US National Cancer Institute.879596 Since then, about a dozen of different early phase clinical trials have been conducted on BCMA CAR T treatment for advanced multiple myeloma.9798 A detailed review outlining the differences in the construct, manufacturing, and clinical efficacy of these different products has been published previously.8186

This review focuses on four BCMA CAR T cell products that are currently being evaluated in registration (that is, for regulatory approval) phase I/II clinical trials for patients with relapsed and refractory multiple myeloma. These products include bb2121 (now known as idecabtagene vicleucel or ide-cel), JCARH125 (now known as orvacabtagene autoleucel or orva-cel), LCAR-B38M (now known as JNJ-4528), and P-Bcma-101. FDA approvals for some of these agents are anticipated in 2020-21 for relapsed and refractory multiple myeloma (fig 5; table 2). The high overall response rates of 60-100% seen in these trials in a highly refractory population is unprecedented, although the durability of these responses is still in question.

Four major constructs of chimeric antigen receptor (CAR) T cells targeting B cell maturation antigens (BCMA), currently in multicenter clinical trials investigating multiple myeloma. This figure does not include all BCMA constructs in multiple myeloma. ScFv=single chain variable fragment; VH only=variable-heavy chain only fragments

Summary of major multicenter clinical trials investigating multiple myeloma treatments*

The most advanced CAR T cell treatment targeting a BCMA is ide-cel (bb2121), which uses a lentiviral vector for CAR insertion and includes a 4-1BB costimulatory domain as well as a murine single chain variable fragment.114 In a phase I non-randomized, open label, multicenter trial in relapsed and refractory multiple myeloma (3 prior lines of treatment) for 33 patients treated at various doses,115 researchers found an overall response rate of 85% with a median progression free survival of 11.8 months. A higher overall response rate was seen at the higher dose levels and doses of 150-450106 CAR T cells were defined as the active dose.115 This dose is being tested currently in a multicenter, single arm, open label trial to evaluate bb2121 CAR T cells further in relapsed and refractory multiple myeloma; the trial has completed enrolment of 149 patients worldwide. Preliminary results show an overall response rate of 73% (complete response rate 33%) and median progression free survival of 8.8 months in 128 patients treated at doses of 150-450106 cells (table 2).99 Fifty four patients treated at the highest dose level of 450106 cells had an overall response rate of 82% and a median progression free survival of 12.1 months.99 These results have been submitted to regulatory agencies including the FDA and European Medicines Agency for treatment for advanced multiple myeloma.

Orva-cel (JCARH125) is another second generation CAR product with a fully human B cell derived single chain variable fragment, a 4-1BB costimulatory domain, and optimized manufacturing (predefined CD4:CD8 ratio) that is derived from preclinical work at Memorial Sloan Kettering Cancer Center. The preliminary data for the multicenter phase I/II EVOLVE study were presented at the American Society of Clinical Oncology meeting in 2020. These patients had received a median of six prior treatments. They received escalating doses of 50-600106 cells. The results for 62 patients treated at the 300-600106 cells dose range showed an overall response rate of 92% (complete response rate 36%).100101 The trial is currently enrolling at the recommended phase II dose of 600106 cells (table 2).

The LCAR-B38M CAR construct was developed initially in China and is currently being pursued in the US and globally as JNJ-4528 (table 2). It consists of two llama derived variable-heavy chain only fragments that target two epitopes of BCMA designed to confer avidity. In a phase I/II study in China, researchers found deep durable responses with a median progression free survival of 19.9 months and a manageable safety profile in relapsed and refractory multiple myeloma, although the patients in this study were treated earlier in their disease course with a median of three prior lines of treatment and were therefore less heavily pre-treated.102103104105 In the US and Europe, a multicenter phase Ib/II clinical trial of this CAR construct as JNJ-4528 in relapsed and refractory multiple myeloma (3 prior lines of treatment) was conducted to confirm the findings of the LEGEND-2 study. Preliminary results of the phase Ib portion showed an overall response rate of 100% (complete response rate 86%) in patients with a median of five prior lines of treatment (table 2).106107 The phase II portion is fully enrolled, and phase II and III studies have been initiated.

P-BCMA-101 is uniquely manufactured using the non-viral piggyBac gene editing system, which is less costly, produces cells with a high percentage of favorable stem cell memory phenotype T cells, and has the ability to include a safety switch. The binding molecule for this product is not a single chain variable fragment but a small fully human fibronectin domain (Centyrin) that has higher specificity and potentially less immunogenicity. In a phase I dose escalation trial, the overall response rate was 63% with a median progression free survival of 9.5 months in 19 evaluable patients108 (table 2).

CAR T cell treatments have a unique toxicity profile where patients can develop side effects such as cytokine release syndrome and neurotoxicity that has been recently termed immune effector cell associated neurotoxicity syndrome (ICANS).116 Cytokine release syndrome has been defined as a disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, or hypoxia caused by the release of cytokines from cells. The American Society for Transplantation and Cellular Therapy has developed a consensus grading system for cytokine release syndrome, which depends on the severity and presence of fever, hypotension, or hypoxia (table 3).116

American Society for Transplantation and Cellular Therapy consensus grading for cytokine release syndrome (CRS)116

ICANS has been defined as a disorder involving the central nervous system following any immunotherapy that results in the activation or engagement of endogenous or infused T cells or other immune effector cells. Symptoms or signs can be progressive and could include aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral edema.116 It includes four grades that are determined by the ICE score (immune effector cell associated encephalopathy score, which provides objectivity to grading encephalopathy), level of consciousness, seizure, motor findings, and elevated intracranial pressure or cerebral edema (table 4).116 Management of ICANS and cytokine release syndrome is based on grading and involves supportive care, steroids, and interleukin blocking agents.117118 Interleukin 6 blocking agents (tocilizumab and siltuximab) with or without steroids are the mainstay of management for cytokine release syndrome, whereas steroids are the mainstay for the management of neurotoxicity. Another potential agent for managing these symptoms includes the interleukin 1 blocking agent anakinra.119

American Society for Transplantation and Cellular Therapy consensus grading for immune effector cell associated neurotoxicity syndrome (ICANS) in adults116

All the clinical trials on BCMA CAR T cell treatments had a high incidence of cytokine release syndrome (>80%) except for P-BCMA-101, which seemed to have a substantially lower incidence (10%). Despite this, severe cytokine release syndrome (that is, grade 3) is seen in less than 10% of patients. Neurotoxicity was reported in less than 20% of patients with severe neurotoxicity (grade 3) in less than 7% of patients. Another common side effect is cytopenia, which has also been thought to be secondary to the lymphodepleting chemotherapy, ongoing CAR T cell activity, and disruption of hematopoiesis showing severe hypocellularity in the bone marrow, but most patients recover with time.120121

Early recognition of cytokine release syndrome and ICANS and prompt intervention after CAR T cell treatment is vital to prevent serious consequences, although the optimal timing for intervention and benefit of prophylactic treatment is yet unknown.122 The CAR T cell therapy associated toxicity (CARTOX) working group has developed a management approach for these syndromes, based on multidisciplinary grades.123 In cytokine release syndrome, patients with grade 1 are usually managed with supportive care, those with grade 2 are managed with the anti-interleukin 6 receptor tocilizumab with or without steroids in addition to supportive care, and those with grade 3-4 are managed in the intensive care unit with aggressive supportive care, vasopressors, oxygen, tocilizumab, and steroids. Patients with grade 1 and 2 ICANS are managed supportively but an electroencephalogram is done to rule out electrical seizures and imaging of the brain to rule out edema. Patients with grade 3 and 4 ICANS need steroids and more aggressive supportive care.120

Bispecific monoclonal antibodies direct a hosts immune system (more specifically cytotoxic T cells) against cancer cells by binding CD3 on T cells with a target protein on cancer cells (fig 6).124 A type of bispecific antibody is the bispecific T cell engager (BiTE), which differs from other bispecific antibodies by containing two different single chain variable fragments connected by a linker. BiTEs often have a short half life, requiring continuous infusion to maintain efficacy.125 The first BiTE to receive FDA approval for treatment in relapsed and refractory acute lymphoblastic leukemia is Blinatumomab, a bispecific antibody that engages T cells to CD19 positive cells.126 Because BiTEs engage and activate the patients own immune cells, they have a toxicity profile similar to CAR T cells including cytokine release syndrome and ICANS.116

Structure of a bispecific antibody. BiTEs=bispecific T cell engagers

AMG 420 (previously named BI 836909) is a novel BiTE targeting BCMA on myeloma cells and CD3 on T cells, which has induced multiple myeloma cell lysis in preclinical models.127 In the first-in-human phase I study of AMG 420 in patients with at least two lines of treatment, AMG 420 was given as a continuous infusion with a pump for four week infusions, six week cycles, and a maximum of 10 cycles. The maximum tolerated dose was 400 g/day; seven (70%) of 10 patients responded to this dose. Serious adverse events were seen in 48% of patients, which were most commonly infections; and two patients had reversible grade 3 polyneuropathies. Cytokine release syndrome developed in 38% of patients, with no toxicity in the central nervous system.109 A phase Ib trial with AMG 420 is currently ongoing and although this drug looks promising, the continuous intravenous infusions present logistical challenges for patients and healthcare systems (table 2). AMG 701 is a modified version of AMG 420 (by addition of an Fc domain) with an extended half life that is suitable for dosing once a week and is being investigated in a phase I study.128

Another BCMA bispecific antibody, CC-93269, is being studied in an ongoing phase I clinical trial. This humanized 2+1, immunoglobulin G 1 based, T cell engager binds to BCMA bivalently on myeloma cells and CD3 monovalently on T cells. The bivalent binding could lead to improved potency, tumor targeting, and retention.129 All doses (range 0.15-10 mg) were given intravenously over two hours weekly for the first three cycles, every two weeks for the next three cycles, and then monthly. The most common treatment emergent adverse events of grade 3 or higher included neutropenia, anemia, and infections. Cytokine release syndrome was seen in 77% of patients, with all events developing after the first dose and less common with subsequent doses. The incidence increased with higher doses, and only one patient had cytokine release syndrome of grade 3 or higher leading to their death. In 30 patients treated, the overall response rate was 43.3% and dose dependent. The overall response rate was 88.9% in nine patients in the highest dose cohort.110

Teclistamab (JNJ-64007957) is a humanized, immunoglobulin G-4 based, bispecific DuoBody antibody that binds to BCMA and CD3 that is being studied in a phase I clinical trial. In the dose escalation part, 78 patients received doses ranging from 0.3 g/kg to 720 g/kg. The drug is given intravenously every week, with one to three step-up doses given within one week before the full dose. The overall response rate was dose dependent with no responses at doses 0.3-19.2 g/kg, 30% at 38.4-180 g/kg, and 67% at 270 g/kg. Cytokine release syndrome was seen in 56% of patients overall and 65% patients at doses over 38.4 g/kg. The most common adverse events at grade 3 or higher that were related to treatment were cytopenias and infections (table 2).111

Antibody drug conjugates are complex molecules composed of an antibody that targets cancer cells and are linked to a biologically active cytotoxic drug (known as the payload; fig 7).125 Belantamab mafodotin (GSK2857916) is a novel humanized and afucosylated (to improve antibody dependent cell mediated cytotoxicity) antibody drug conjugate that targets BCMA. It consists of an anti-BCMA monoclonal antibody conjugated to monomethyl auristatin F, a potent microtubule inhibitor.130 This antibody drug conjugate was shown to have selective myeloma cell killing in vitro and in vivo thus setting the stage for clinical trials.130131

Structure of an antibody drug conjugate

This antibody was studied in a two part phase I study. The drug was well tolerated with no dose limiting toxicities, although corneal events (such as blurry vision, dry eyes, photophobia) were seen in about 58% of patients; these events are a known toxicity of monomethyl auristatin F.132 In the dose expansion phase, 35 patients were treated, and the overall response rate was 60% with a median progression free survival 12 months.133 In a phase II, two arm study, the antibody was used in patients with relapsed and refractory multiple myeloma who had failed at least three lines of treatment. The overall response rate was 31% at the 2.5 mg/kg dose and 34% at the 3.3 mg/kg dose, which was significantly lower than the phase I study. The corneal changes or keratopathy were seen in 70% and 75% of patients, respectively. Owing to the similar response rates with the 2.5 mg/kg and 3.3 mg/kg doses and a more favorable side effect profile with the lower dose, 2.5 mg/kg will be the dose used for future studies.112 Based on these data, belantamab is the first anti-BCMA treatment to be FDA approved for relapsed and refractory multiple myeloma patients who have received four prior treatments including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.

Preliminary results for another study with 18 patients treated on the belantamab, bortezomib, and dexamethasone arm was presented recently, with an overall response rate of 78%; however, all 18 patients developed grade 1-3 keratopathy.113 This visual toxicity is a unique but potentially serious side effect to this drug that needs close monitoring with an ophthalmologist. Another antibody drug conjugate, DFRF4539A, is an anti-FcRH5 (also known as FcRL5) antibody conjugated to monomethyl auristatin and has shown limited activity and high incidence of toxicity in a phase I study; therefore, it was unsuccessful for this disease (table 2).134135

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Emerging immunotherapies in multiple myeloma - The BMJ

Bone Marrow Stem Cells Comments Off on Emerging immunotherapies in multiple myeloma – The BMJ | September 21st, 2020

As induction therapies continue to improve the depth of response (DOR) in patients with multiple myeloma, it may be possible to eliminate the need forautologous stem cell transplant (ASCT) in this population, provided that deep responses with up-front therapy can be achieved, according to Jeffrey Wolf, MD.

There are a lot of reasons I would like to get rid ofautologous stem cell transplants, Wolf said. Newer drugs and newer regimens are going to allow us to get there, [provided] we [conduct] the right studies.

There has been notable growth of induction therapies within the myeloma space, particularly with regard to triplet regimens, such as lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd), as well as carfilzomib (Kyprolis), lenalidomide, and dexamethasone (KRd). Daratumumab (Darzalex) is also making great progress by quickly moving to the frontline setting for patients who are transplant ineligible, as well as for older patients who appear to tolerate the agent well, Wolf explained.

Its possible that as our induction therapies improve over the next few years, we may be able to eliminateautologous stem cell transplantation as a form ofconsolidationif we [can] get deep responses, such as minimal residual disease (MRD) [negativity] with just our initial induction therapy, said Wolf.

In an interview with OncLive, Wolf, a clinical professor within the Department of Medicine at University of California, San Francisco (UCSF) and director of the Myeloma Program at the UCSF Helen Diller Family Comprehensive Cancer Center, discusses treatment options for patients with myeloma, in addition to how MRD can be used to inform clinical decisions and improve patient outcomes.

OncLive: Could you discuss the evolution of induction therapy in multiple myeloma?

Wolf: Induction therapy for myeloma has evolved tremendously over the past few years, [especially] triplet induction [regimens, such as] RVd or KRd,based on recent studies. Daratumumab is certainly making a rapid move to be included in [frontline] therapy, especially in patients who are not eligible for transplant. It seems [that if the agent is] appropriate for them, it could be appropriate for younger patients, as well, but we dont have an FDA approval [in younger patients yet].

The goal [of treatment] is DOR, [which] is measured byMRD.

What are some of the strategies that are being used for transplant-eligible and -ineligible patients with newly diagnosed disease?

One of the main studies I presented [during my talk] was the ENDURANCE trial, which was just presented at the 2020 American Society of Clinical Onccology Virtual Meeting. The trial was what we thought of as somewhat of a flawed study that [claimed] RVd and KRd were equivalent for progression-freesurvival (PFS) [in transplant-eligible patients]. The problem is that most patients move on to transplant. What we really should have been looking at was KRd plus transplant versus RVd plus transplant. [The studys design] eliminated patients from the analysis when they underwent transplant.

In the transplant-ineligible setting, there are a lot more studies to refer to, including the studies that moved daratumumab to the frontline setting. Initially, we learned that maintenance lenalidomide was necessary even in patients who are not posttransplant. Another study showed thatdaratumumab added to bortezomib, melphalan, and prednisone(VMP) really improved PFS and overall survival (OS). Of course, [there is also the study that evaluated]daratumumab plus lenalidomide and dexamethasone (Rd) versusRd, [whereby] daratumumab adds tremendous depth and durability.

This morning I put 2 older patients on that regimen. They tolerateddaratumumab quite well and can get a DOR that is equivalent to that of a patient who undergoes transplant.

How are you navigating among the agents that are currently available in practice?

It seems complicated because there are so many options, but it tends to sort itself out by circumstance. For example, this morning I saw a transplant-ineligible patient who didnt getMedicare Part D and, therefore, I couldnt give them oral therapies such aslenalidomide. Their referring doctor gave them cyclophosphamide, bortezomib, and dexamethasone (CyBorD), which is all [intravenous]. This morning I decided to switch them tosubcutaneous daratumumab, bortezomib,dexamethasone.

Most of these regimens will give you the same responses. I often start with preexisting conditions to decide which drugs I eliminate and which drugs Im going to use instead.

What is the role of transplant in this space right now? Will transplant retain its role in future?

I started out as a transplanter 40 years ago, so its hard to say this, but Ive been thinking for the past decade that were on the verge of getting rid ofautologous stem cell transplant from myeloma. If our induction therapies are so effective, we may be able to eliminate transplant. Id like to see us conduct trials, such as the MASTER trial, led by Luciano Costa, MD, PhD, of the University of Alabamas Birmingham School of Medicine, in which patients who achieve MRD [negativity] with induction therapy do not proceed to transplant. Were going to have to do those kinds of studies to eliminate transplant. Its a fairly primitive kind of therapy in that we give high-dose therapy to wipe out as much myeloma as we can, and in doing so wipe out vulnerable bone marrow. Then, we have to [transplant] frozen stem cells from the patient. [The alkylator] leads to increased risk of secondary malignancies. Patients lose their hair, they get sick for 2 or 3 months, and theyre immunocompromised, which is not a good thing to be these days.

How might MRD be used to optimize patient outcomes?

In the world of myeloma, experts are divided over whether to use MRD to make decisions. I happen to be in the group [in favor of MRD]. Its no different than usingmonoclonal spike (m spike) orlight chain measurements to make decisions. Were already using MRD in chronic lymphocytic leukemia andacute lymphocytic leukemia to make decisions. The only restriction in myeloma is that, so far, weve only been able to [evaluate MRD with] bone marrow and not blood. If we can start measuring MRD in myeloma [through] blood, it would be as commonly used as light chain or m spike measurements to make these decisions. Itll help us immeasurably because most of the time were getting patients into complete remission (CR)which it really isnt CRand then we keep them on regimens for maintenance.

For example, when we dont know what were accomplishing, [its worth asking], Are patients getting better? Are patients staying the same? Is the MRD going up while were treating patients with drugs that clearly arent working? Should we be switching therapies? For patients who are MRD [negative] year after year, is there any reason why we have them on these therapies that are so costly and have so many adverse effects (AEs) and secondary malignancies? There are all kinds of reasons as to why we should be using MRD for measurement. I would argue that the only reason why we arent using MRD is because we have to [evaluate] it in bone marrow, which is a little more uncomfortable compared with blood, and maybe because the studies havent been completed yet. Its only a matter of 1 or 2 years before we will be using MRD to make clinical decisions. In terms of frontline therapies, using MRD might allow us to [avoid] transplant or indicate when weve given enough treatment and is time to move to maintenance. There a lot of possibilities to using MRD instead of just historically saying, this is how we do it.

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Improved Induction Therapies Could Eliminate the Need for Transplant in Myeloma - OncLive

Bone Marrow Stem Cells Comments Off on Improved Induction Therapies Could Eliminate the Need for Transplant in Myeloma – OncLive | September 20th, 2020

When youre in pain, its important to find effective, long-lasting solutions that can provide short recovery periods. This is what regenerative medicine offers. Over the past decade, there has been a growing field of medicine that utilizes the bodys own healing capabilities using platelet-rich plasma and mesenchymal stem cells (MSCs). This growing field is labeled as regenerative medicine. Regenerative therapies focus on healing and help regrow damaged tissue naturally. Regenerative injection therapy is used to provide relief to musculoskeletal injuries that involve damage to ligaments, tendons, cartilage, joints, and discs.

Watch video of PRP:

PRP therapy on Better CT

PRP is safeas we are using what your body naturally produces, concentrating the desired critical components and transplanting them into the affected area for effective tissue regeneration and healing. There is no risk of rejection and very minimal overall procedural risk.

FDA regulations do not allow for the cloning of stem cells or growing them in a lab. Also, stem cells derived from fat cells are not approved by the FDA as it does not allow for manipulation. This leaves us to another rich stem cell source in our body which is bone marrow. Stem cells exist in our bodies and are rudimentary cells that can differentiate into other cells.

Think of bone marrow stem cells as the mother cell that is responsible for producing new blood cells. Bone marrow contains hundreds of growth factors and is often used for severe degenerative conditions or where PRP therapy may not be sufficient to provide the growth factors needed to provide relief.

Lastly, there are many offshoot therapies that use biologics derived from placental tissue or blood cord. These biologics are sometimes marketed as Stem cells but are not stem cells and contain zero viable cells. What they contain are growth factors that can also aid when combined with PRP or Stem Cells derived from your own body.

MSCs and PRPmay be used to target a number of conditions that could benefit from their healing and regenerative qualities. Especially when considering chronic pain, alternative solutions may be necessary if it has been difficult to find relief. Along with generalized joint pain, MSCs and PRPmay be used to target:

With so many options for joint pain out there, you may be wondering what benefits choosing stem cell therapy provides. Overall, because mesenchymal stem cell therapy utilizes biologic material harvested directly from the patients body, the general benefits include minimal risk, minimal recovery time, and minimal worry:

Avoid surgery and its many complications and risks: Stem cell therapy is a minimally invasive, non-surgical procedure.

Minimal post-procedural recovery time: One of the most time-consuming factors of any injury is not always the treatment itself, but actually the recovery time. With stem cell therapy, recovery time is minimal.

No risk of rejection: Due to using biologics extracted from the patient, there is no risk of rejection.

No communicable disease transmission: As the cells originate within your own body, there is no risk of spreading disease from or to another person.

If you are suffering from joint pain, back pain, or a debilitating condition like osteoarthritis, it is important to consider all of your available options. Our elite team of professionals can determine if you are the right candidate for MSCs. If youre interested in learning more, contact us today.

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Regenerative Therapy by Dr. Roshni Patel on Better CT - Farmington, CT - Patch.com

Bone Marrow Stem Cells Comments Off on Regenerative Therapy by Dr. Roshni Patel on Better CT – Farmington, CT – Patch.com | September 20th, 2020

Differences in biological sex can dictate lifelong disease patterns, says a new study by Michigan State University researchers that links connections between specific hormones present before and after birth with immune response and lifelong immunological disease development.

Published in the most recent edition of the Proceedings of the National Academy of Sciences, the study answers questions about why females are at increased risk for common diseases that involve or target the immune system like asthma, allergies, migraines and irritable bowel syndrome. The findings by Adam Moeser, Emily Mackey and Cynthia Jordan also open the door for new therapies and preventatives

This research shows that its our perinatal hormones, not our adult sex hormones, that have a greater influence on our risk of developing mast cell-associated disorders throughout the lifespan, says Moeser, Matilda R. Wilson Endowed Chair, professor in the Department of Large Animal Clinical Sciences and the studys principle investigator. A better understanding of how perinatal sex hormones shape lifelong mast cell activity could lead to sex-specific preventatives and therapies for mast cell-associated diseases.

Mast cells are white blood cells that play beneficial roles in the body. They orchestrate the first line of defense against infections and toxin exposure and play an important role in wound healing, according to the study, Perinatal Androgens Organize Sex Differences in Mast Cells and Attenuate Anaphylaxis Severity into Adulthood.

However, when mast cells become overreactive, they can initiate chronic inflammatory diseases and, in certain cases, death. Moesers prior research linked psychological stress to a specific mast cell receptor and overreactive immune responses.

Moeser also previously discovered sex differences in mast cells. Female mast cells store and release more inflammatory substances like proteases, histamine and serotonin, compared with males. Thus, female mast cells are more likely than male mast cells to kick-start aggressive immune responses. While this may offer females the upper hand in surviving infections, it also can put females at higher risk for inflammatory and autoimmune diseases.

IBS is an example of this, says Mackey, whose doctoral research is part of this new publication.

While approximately 25% of the U.S. population is affected by IBS, women are up to four times more likely to develop this disease than men.

Moeser, Mackey and Jordans latest research explains why these sex-biased disease patterns are observed in both adults and prepubertal children. They found that lower levels of serum histamine and less-severe anaphylactic responses occur in males because of their naturally higher levels of perinatal androgens, which are specific sex hormones present shortly before and after birth.

Mast cells are created from stem cells in our bone marrow, Moeser said. High levels of perinatal androgens program the mast cell stem cells to house and release lower levels of inflammatory substances, resulting in a significantly reduced severity of anaphylactic responses in male newborns and adults.

We then confirmed that the androgens played a role by studying males who lack functional androgen receptors, says Jordan, professor of Neuroscience and an expert in the biology of sex differences.

While high perinatal androgen levels are specific to males, the researchers found that while in utero, females exposed to male levels of perinatal androgens develop mast cells that behave more like those of males.

For these females, exposure to the perinatal androgens reduced their histamine levels and they also exhibited less-severe anaphylactic responses as adults, says Mackey, who is currently a veterinary medical student at North Carolina State University.

In addition to paving the way for improved and potentially novel therapies for sex-biased immunological and other diseases, future research based will help researchers understand how physiological and environmental factors that occur early in life can shape lifetime disease risk, particularly mast cell-mediated disease patterns.

While biological sex and adult sex hormones are known to have a major influence on immunological diseases between the sexes, were learning that the hormones that we are exposed to in utero may play a larger role in determining sex differences in mast cell-associated disease risk, both as adults and as children, Moeser said.

For more information on Moesers research, go to the Gastrointestinal Stress Biology Laboratory. Also, visit the MSU College of Veterinary Medicines website for more about its research efforts.

(Note for media: Please include the following link to the study in all online media coverage: https://www.pnas.org/content/early/2020/09/10/1915075117)

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New research connects the hormones we're born with to lifetime risk for immunological diseases - MSUToday

Bone Marrow Stem Cells Comments Off on New research connects the hormones we’re born with to lifetime risk for immunological diseases – MSUToday | September 20th, 2020

By InYourArea Community

The three generations of the Taylor family, Allan, Corey and Chris.

Three generations of a lifesaving family have defied the odds by being selected to donate their bone marrow to three complete strangers thousands of miles away.

Allan, Chris and Corey Taylor were all selected from the Welsh Bone Marrow Donor Registry as the only suitable matches in the world capable of saving patients from Africa, America and Europe respectively.

To mark World Bone Marrow Donor Day on Saturday, September 19, the Taylor family from Pontypool, Torfaen, is calling on 17-30 year olds across Wales to volunteer their lifesaving bone marrow by joining the Welsh Bone Marrow Donor Registry.

Chris Harvey, Head of the Welsh Bone Marrow Donor Registry, said:

Every day blood cancer patients around the world are desperately hoping to find a suitable bone marrow match. The requirements needed to match a patient with a bone marrow donor are very specific and this sadly means three in ten patients will never find the potentially lifesaving bone marrow donor they need.

Last year 50,000 donations were made from around 40 million volunteers signed up internationally, which shows just how rare it is to be someones match.

The Taylors really are a family of lifesavers.

Bone marrow is the soft, spongy tissue found at the centre of certain bones in your body where blood stem cells live. Blood stem cells produce all your essential blood cells, such as red blood cells to carry oxygen and white blood cells to fight infection. There are some diseases, such as some forms of leukaemia, which stop bone marrow working properly. For these patients, the best hope of recovery is to receive a bone marrow transplant.

Talking of his experience, 65 year old Allan, the eldest of the Taylor family donors said: A lot has changed since I donated back in 2005 but the constant has been the fantastic Welsh Bone Marrow Donor Registry staff who are always at hand throughout the process to look after you and to offer you reassurance and support.

Chris, 33, and the middle generation of the three donors, who currently works for Torfaen Council, recounted his experience: I was already a blood donor and decided one day to sign up to the Welsh Bone Marrow Donor Registry. I am a big Superman fan so Ive always dreamed of being a superhero. I cant fly but I was able to save a life by giving my bone marrow its as close as Ill ever get to being a hero!

My employer was absolutely fantastic and couldnt have been more supportive. The procedure, which lasted about four hours, was absolutely fine. After my donation I stayed for about 30 minutes, had a cup of tea and then I went home. I rested over the weekend and was straight back to work on the Monday.

The youngest donor in the family, 25 year old Corey, added: Theres a massive misconception and stigma out there around the bone marrow process. People seem to think they have to go through an operation type medical procedure which involves taking the bone marrow directly from your hip bone.

The reality is quite different as 85% of donations are collected through a non-surgical procedure very similar to a blood donation, it just takes a little longer and theres very little discomfort.

The PBSC process collects stem cells directly using a specialist machine. The process involves drawing blood out of one arm, extracting the stem cells, before returning the remaining blood to your other arm. Donors typically return to normal activity a day or two following the donation.

Allan Taylor summed up their achievement by saying:

I know people can talk about giving money but I think we have done something much more than that, we have potentially given three people the gift of life. You cant put a price on that! Ive done what I can. You can too.

If you are aged 17-30, do something amazing, join the Welsh Bone Marrow Donor Registry. Simply, book to give blood or call the Welsh Blood Service on 0800 252 266.

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Pontypool family gives three lifesaving bone marrow donations - In Your Area

Bone Marrow Stem Cells Comments Off on Pontypool family gives three lifesaving bone marrow donations – In Your Area | September 18th, 2020

Its already hard enough for blood cancer patients to find a match through the international bone marrow registry, which pairs patients with potential donors who have the right type of tissue. But if youre Black and Jewish?

For people with multiple ethnic backgrounds who need marrow or stem cell transplants, matching is even harder.

I remember the doctor saying something like if he was an Irish white boy from Ireland, he might have a better chance, Monika Clark said about her son, 24-year-old Jordan Jackson-Clark of Oakland.

Jackson-Clark, whom his mom describes as mixed ethnicity and biracial, is likely to need a bone marrow transplant after a diagnosis of leukemia two weeks ago.

It was so out of the blue, Clark said. It was so unexpected.

Jackson-Clark had experienced a few bouts of intense stomach pain over the past summer, one strong enough to send him to the ER. Clark was concerned, but she was never expecting the recent call that they got from the doctor.

Through tears, Clark described the blow of hearing the diagnosis for her son, a Berkeley High School grad who was a camp counselor at the East Bay JCC and a member of the Jewish fraternity AEPi.

Hes just a gentle, loving young man, she said.

Jackson-Clark has acute myeloid leukemia, a cancer of the blood and bone marrow. Hes in the hospital getting chemotherapy for the next few weeks. In the meantime, knowing how difficult it will be to find a match for her son, Clark is desperately trying to get the word out about the bone marrow registry.

Please step out and do something very simple to save a life, she said.

The ethnic background of a cancer patient who needs a transplant matters, because the markers used to match a donor and patient are inherited. Having the same markers as a donor makes it a lot more likely that the patients body will accept the life-saving bone marrow or stem cells.

But the makeup of the database of potential donors is mostly white. For people of color and mixed race, the percentage of matches is 23 percent, and for white Caucasians its 77 percent, Clark said.

According to the nonprofit Gift of Life, while more than 12 percent of the American population is Black, only 4 percent on the registry are, and the percentages are similarly out of proportion for other ethnic groups.

Gift of Life was founded by Jay Feinberg, who was diagnosed with leukemia more than 20 years ago and needed a bone marrow transplant from a white Ashkenazi Jew. He sought a donor match, but at that time the database was sorely lacking in diversity. Efforts since then by his organization and others have greatly increased ethnic representation in the registry, but matches for mixed-ethnicity patients remain scarce. Jackson-Clark has the best chance of being matched with another person who is Black, white and Ashkenazi, but there simply arent many in the database.

The solution is getting more potential donors into the system. Clark is asking people to get tested with a simple cheek swab through Be the Match or any other registration service not only if they think they might be a match for her son, but also for all of the other patients out there who need matches. Optimal donor ages are 18 to 44; registration is free and can be done through the mail. That puts them on the international registry of potential donors, and the more people who are on the list, the more likely it is that they could be a match for a cancer patient.

Thats why Rabbi Yigal Rosenberg of Chabad of Santa Clara held a registration drive in February and encouraged young people to get on the list. When he got a call from Gift of Life a few days later, he thought it had something to do with the event.

They said, actually, you are a match! he said.

Rosenberg had the right kind of stem cells to help a 40-year-old man based on a swab hed given 10 years previously in New Jersey. (Whether marrow or stem cells are donated depends on the patients treatment needs.)

Im like, what are the chances? Rosenberg said. Literally I just hosted an event two days ago!

He immediately said yes and began a required series of injections to boost stem-cell production checking with another rabbi to make sure it was OK to have the shots on Shabbat as well.

This is the one thing youre allowed to compromise on, in Shabbat observance, is to save a life, he said.

Then, at the beginning of September, he drove down to San Bernardino, where he was put up in a hotel. He spent one day at the donation center attached to a machine that pumped blood out, filtered out and collected the stem cells, and returned the blood to his body. Rosenberg said the experience wasnt difficult at all.

I just felt so empowered during the entire process, he said.

He even livestreamed it on Facebook as a way to encourage more registrations, and to dispel some of the fear around donation. (Whether a patient requires the donors marrow or stem cells depends on the particular treatment protocol.)

I went right back to the hotel, jumped in the Jacuzzi for a bit and took a nap, he said. The next day he was back on his way to Santa Clara to resume his duties.

Clark, a former JCC preschool teacher, said it is important for people to know that donating stem cells and even bone marrow is not as intrusive or painful as it used to be. And anyone on the registry can always decide later that theyre not ready to donate, so getting the swab does not commit them to doing so.

The greatest Rosh Hashanah gift from the Jewish and biracial communities would be to spread the word far and wide with your communities, and to please get on the donor list by sending away for a simple and free cheek swab, she said. You just might save my or someone elses childs life.

Read more:
Oakland 24-year-old seeking multiethnic bone marrow donor - The Jewish News of Northern California

Bone Marrow Stem Cells Comments Off on Oakland 24-year-old seeking multiethnic bone marrow donor – The Jewish News of Northern California | September 18th, 2020

"It was like a curtain dropping over your eyes when youre going into the dark," Debbie Ramirez, Odessa resident said.

ODESSA, Texas Debbie Ramirez wakes up every morning just like you and I do.

She brushes her hair, like you and I do. She puts on mascara.

And then she puts on her shoes, just like you and I do.

Except, she doesn't get ready the way you and I do. That's because Debbie Ramirez is blind.

"I can see me moving my hand right in front of me, but right here I don't see anything," Debbie Ramirez, Odessa resident said.

It was six years ago when Debbie's life changed.

"It was like a curtain dropping over your eyes when you're going into the dark," Ramirez said.

That darkness not only took her sight. Debbie lost 75% of her memory and with it most of her life.

For years she sought out help from doctors. But none had an answer.

"They all told me they didn't know why I went blind. Nobody could explain it," Ramirez said.

"I thought how am I going to live like this? I've seen my entire life, I don't know how to live blind," Ramirez said.

Then one day, a phone call changed her life once again.

"I had a very large tumor. It was the size of an orange," Ramirez said.

An Odessa doctor finally had an answer. But what would come next was worse than you could imagine.

"He rushed me to Dallas by ambulance because he said I had less than 30 days to live," Ramirez said.

Her thoughts went straight to her family.

"My children are everything," Ramirez said.

And what would happen if she didn't make it through the surgery?

But the surgery was a success. The tumor was gone.

"I was me again and I just wanted to move on with life and grasp it because I had been given a second chance," Ramirez said.

Her memory started to come back, the pain and the headaches faded away, and Debbie began to take charge of her life again.

She re-learned how to cook, clean and even how to do laundry.

And now Debbie has a chance to get her sight back through a clinical trial in Florida.

"I am just really hoping to get my sight back more than anything. It's been the hardest thing I've ever gone through," Ramirez said.

The trial would use neurons from bone marrow to generate new stem cells in her retina and optic nerves. But there's one more roadblock before Debbie can see her children and grandson.

"It's a lot of money and my insurance will not cover it because it has to do with stem cell therapy," Ramirez said.

But Debbie said she's not giving up.

Although Debbie can't see, she says one thing is clear to her.

"I feel like God has always been beside me," Ramirez said.

________________________________________________________________

If you'd like to help Debbie with her mission to get her sight back, you can reach out to her directly at 432-212-5726.

She said she will take any help she can get!

Original post:
Odessa woman hopes to gain back her sight after 6 years of being blind - NewsWest9.com

Bone Marrow Stem Cells Comments Off on Odessa woman hopes to gain back her sight after 6 years of being blind – NewsWest9.com | September 18th, 2020

Fort Collins, Colorado The report on the Stem Cell Therapy Market provides an in-depth assessment of the Stem Cell Therapy market including technological advancements, market drivers, challenges, current and emerging trends, opportunities, threats, risks, strategic developments, product advancements, and other key features. The report covers market size estimation, share, growth rate, global position, and regional analysis of the market. The report also covers forecast estimations for investments in the Stem Cell Therapy industry from 2020 to 2027.

The report is furnished with the latest market dynamics and economic scenario in regards to the COVID-19 pandemic. The pandemic has brought about drastic changes in the economy of the world and has affected several key segments and growth opportunities. The report provides an in-depth impact analysis of the pandemic on the market to better understand the latest changes in the market and gain a futuristic outlook on a post-COVID-19 scenario.

Global Stem Cell TherapyMarketwas valued at 117.66 million in 2019 and is projected to reach USD255.37 million by 2027, growing at a CAGR of 10.97% from 2020 to 2027.

Get a sample of the report @ https://reportsglobe.com/download-sample/?rid=33553

The report provides an in-depth analysis of the key developments and innovations of the market, such as research and development advancements, product launches, mergers & acquisitions, joint ventures, partnerships, government deals, and collaborations. The report provides a comprehensive overview of the regional growth of each market player.

Additionally, the report provides details about the revenue estimation, financial standings, capacity, import/export, supply and demand ratio, production and consumption trends, CAGR, market share, market growth dynamics, and market segmentation analysis.

The report covers extensive analysis of the key market players in the market, along with their business overview, expansion plans, and strategies. The key players studied in the report include:

Furthermore, the report utilizes advanced analytical tools such as SWOT analysis and Porters Five Forces Analysis to analyze key industry players and their market scope. The report also provides feasibility analysis and investment return analysis. It also provides strategic recommendations to formulate investment strategies and provides insights for new entrants.

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The report is designed with an aim to assist the reader in taking beneficial data and making fruitful decisions to accelerate their businesses. The report provides an examination of the economic scenario, along with benefits, limitations, supply, production, demands, and development rate of the market.

1.Stem Cell Therapy Market, By Cell Source:

Adipose Tissue-Derived Mesenchymal Stem Cells Bone Marrow-Derived Mesenchymal Stem Cells Cord Blood/Embryonic Stem Cells Other Cell Sources

2.Stem Cell Therapy Market, By Therapeutic Application:

Musculoskeletal Disorders Wounds and Injuries Cardiovascular Diseases Surgeries Gastrointestinal Diseases Other Applications

3.Stem Cell Therapy Market, By Type:

Allogeneic Stem Cell Therapy Market, By Application Musculoskeletal Disorders Wounds and Injuries Surgeries Acute Graft-Versus-Host Disease (AGVHD) Other Applications Autologous Stem Cell Therapy Market, By Application Cardiovascular Diseases Wounds and Injuries Gastrointestinal Diseases Other Applications

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Regional Analysis of the Market:

For a better understanding of the global Stem Cell Therapy market dynamics, a regional analysis of the market across key geographical areas is offered in the report. The market is spread acrossNorth America, Europe, Latin America, Asia-Pacific, and Middle East & Africa.Each region is analyzed on the basis of the market scenario in the major countries of the regions to provide a deeper understanding of the market.

Benefits of the Global Stem Cell Therapy Report:

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Read more here:
Stem Cell Therapy Market to Witness Exponential Growth by 2020-2027 | Leading Players Osiris Therapeutics, Medipost Co., Anterogen Co., Pharmicell...

Bone Marrow Stem Cells Comments Off on Stem Cell Therapy Market to Witness Exponential Growth by 2020-2027 | Leading Players Osiris Therapeutics, Medipost Co., Anterogen Co., Pharmicell… | September 18th, 2020

Using 3D printers, researchers have collaborated from around the globe to develop nanoclay-based 3D bioprinted scaffolds which could be used to aid skeletal regeneration.

Hailing from the University of Southampton, the Istituto Italiano di Tecnologia in Rome, University Hospital Carl Gustav Carus and Technische Universitt in Dresden, and China Medical University in Taiwan, the researchers 3D bioprinted implantable nanocomposite scaffolds, laden with human bone marrow stromal cells (HBMSCs) and human umbilical vein endothelial cells (HUVECs), which have the potential to facilitate bone formation.

3D bioprinting for orthopedics

Ideally, 3D printed implants of this nature should sustain cell viability and promote cells to multiply, in addition to generating functional constructs shortly after printing and stimulating the host microenvironment to aid tissue growth.

Realistically, bioprinting is in its infancy and the prospect of whole 3D printed transplant organs is still probably decades away. However, there have been a number of innovative developments in the field thus far, such asa novel bio-ink enabling scientists at the University of Minnesota to create a functional 3D printed beating human heart.

Similarly, researchers fromTsinghua Universityhave3D bioprinted brain-like tissue structures capable of nurturing neural cells, while in May microdispensing specialistnScryptand aerospace companyTechShotsuccessfully completed the first functional 3D bioprinting experiment in space a human knee meniscus.

Most recently, researchers from theUniversity of Montrealhave developed a new method of cell bioprinting based on a drop-on-demand technique, called Laser Induced Side Transfer, which utilizes a low energy nanosecond laser and the laws of microfluidic dynamics to jet living cells onto each other. The team believes their work could be adapted for applications such as 3D drug screening models and artificial tissues.

The nanoclay-based method

According to the report,nanoclay-based bioink formulations are particularly attractive for implant applications given their ability, even at low concentrations, to shear while being extruded and regain their shape upon deposition, while shielding cells from potential damage from the printing process.

During the study, scientists harnessed the physiochemical properties of Laponite (LAP), a smectite nanoclay suspension, and combined it with HBMSCs, bone morphogenic protein-2 (BMP-2), and vascular endothelial growth factor to produce LAP-alginate-methylcellulose bioink. HBMSCs, collected from patients undergoing routine hip surgery, and HUVECs, obtained from the umbilical cords of healthy mothers after normal, full-term deliveries, were encapsulated in the bioink and printed using an in-house built bioprinter.

After printing, the scaffolds were incubated for 10 minutes in a sterile calcium chloride solution to enable crosslinking.

The skeletal functionality of the HBMSCs-laden 3D bioprinted scaffolds was investigated in vitro, ex vivo, and in vivo. The results demonstrated significant improvements in mineralized tissue formation with the addition of HBMSCs in 3DP, but not in mold-cast bulk scaffolds.

Significance of the findings

According to the researchers, the printing of bioinks laden with cells that can act as building blocks for the generation of tissue-like structures represents a simple and effective approach to produce readily implantable constructs.

The potential to print stem cells, preserving cell viability, proliferation, and functionality, is currently a key unmet challenge for the biofabrication approach to regenerative medicine. Clay-based bioinks, such as the one looked at in this study, are now proven to offer an attractive vehicle for printing HBMSCs in three-dimensional constructs due to their shear-thinning and inherent functional properties.

Further details of the study can be found in the article titledNanoclay-based 3D printed scaffolds promote vascular ingrowth ex vivo and generate bone mineral tissue in vitro and in vivo, published in the Biofabrication journal. The article is co-authored by Gianluca Cidonio, Michael Glinka, Yang-Hee Kim, Janos Kanczler, Stuart Lanham, Tilman Ahlfeld, Anja Lode, Jonathan Dawson, Michael Gelinsky, and Richard Oreffo.

The 4th annual 3D Printing Industry Awards are coming up in November 2020 and we need a trophy. To be in with a chance of winning a brand newCraftbot Flow IDEX XL3D printer,enter the MyMiniFactory trophy design competition here. Were happy to accept submissions until the 30th of September 2020.

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Featured image shows functional investigation of 3D printed scaffold vascularisation in a CAM model. Image via Biofabrication journal.

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Researchers develop nanoclay-based bioprinting method to produce functional bone implants - 3D Printing Industry

Bone Marrow Stem Cells Comments Off on Researchers develop nanoclay-based bioprinting method to produce functional bone implants – 3D Printing Industry | September 18th, 2020

After Coach Paul Trosclair won a Louisiana high school football championship in December 2018, he and his family walked from the Superdome in New Orleans to celebrate with a bowl of late-night gumbo. He mused about retiring, but no one took him seriously.

For five seasons, Trosclair had endured fatigue and other effects of multiple myeloma, a treatable but incurable blood cancer, missing only a single game. He coached from a golf cart when the burning sensation in his feet made it too painful to stand. And when he was sidelined that one Friday night after a blood clot required surgery, he phoned his players from his hospital bed to wish them luck.

With a state title at Eunice High School, after runner-up finishes there in 1997 and 1998, Trosclair had reached the pinnacle of a long, successful career. He was one of Louisianas winningest coaches. Back home on the Cajun prairie, he rode in a convertible during the towns victory parade, holding the championship trophy. He had nothing left to prove, but he stayed on for the 2019 season, elevating his career record to 247 victories even as medication left him with muscle cramps so severe at times that his fork fell from his fingers.

I couldnt pull the trigger, Trosclair, 64, said in a telephone interview. Its hard to walk away.

Now, he feels compelled, becoming one of a number of older coaches across the country who are choosing to retire rather than risk their health in the coronavirus pandemic.

In June, he gave his retirement notice after 40 years of coaching, the last 25 years at Eunice High. His cancer was in remission but his immune system was compromised. He did not think he could remain safe when a new school year and a new football season began. Not in a locker room where his players dress shoulder to shoulder. Not in the weight room. Not in crowded school hallways.

My doctors thought it was in my best interest not to coach, Trosclair said. I was on the edge; the coronavirus got me to jump over.

While young athletes are considered less vulnerable to Covid-19, the disease caused by the coronavirus, aging coaches are at higher risk of infection and having a severe response. At least 30 high school and club team coaches have died of coronavirus-related causes, according to a search of online obituaries. Though some were in their 70s, one was 27, another 30.

Countless other coaches have been forced to reconsider whether it is worth risking their health to continue their careers.

It remains unclear how many coaches have retired for reasons related to Covid-19. The N.C.A.A., the National Federation of State High School Associations, state athletic associations and coaching organizations said they have not kept such figures.

But a number of states have reported an uptick in teacher retirements, even if it is uncertain how many are related to the coronavirus. Louisiana, for instance, reported 335 retirements in August compared with 196 that month in 2019. In Ohio, the retirement rate more than doubled from July 1 through mid-August, compared to that period a year ago.

More so than in previous years, we are hearing about coaching staff retirees, said Jennifer Mann, a data technician with the Clell Wade Coaches Directory, a well-regarded national networking tool for coaches that tracks collegiate, high school and junior high school sports.

Even so, they may represent a fraction of coaches, though their departures often are deeply felt in their communities.

There are hundreds of thousands of high school coaches across the country in various sports, so even if there are hundreds who have retired, it is a pretty small number, Bruce Howard, a spokesman for the national high school federation, said in an email.

Some coaches who walked away said the pandemic had led them into deep introspection about their safety and their lifes direction.

Norm Ogilvie, 60, Duke Universitys longtime track and field coach, said in a statement that he felt there needs to be a final meaningful chapter for the remaining years I have on our rapidly changing planet.

Mike Fox, 64, retired after 22 years and seven trips to the College World Series as the baseball coach at the University of North Carolina. The coronavirus, he told the school, made him realize it is time for me to be a full-time husband, father and grandfather and do other things with my life.

Updated Sept. 18, 2020

Heres whats happening as the world of sports slowly comes back to life:

Joe Bustos, 57, who won two Arizona state basketball championships in 23 seasons coaching at North High School in Phoenix, stepped down, expressing frustration with virtual teaching and concern after two Arizona teachers died over the summer of Covid-19, including a 61-year-old high school swimming coach.

Im just afraid; I dont want to be playing Russian roulette, Bustos said in an interview. I love coaching and teaching, but at the end of the day youve got to look out for yourself.

Peter Kingsley, 54, taught middle school for nearly three decades in Boulder, Colo., and coached football, basketball, wrestling and track. But he has epilepsy and a circulatory condition that leaves him predisposed to strokes. His wife urged him to retire because of the pandemic. And he was influenced by spending 22 days in hospice with his father, who died this summer of bone cancer.

I had a choice to make whether to potentially die or keep coaching and teaching, Kingsley said in a telephone interview. I just needed to stay safe.

Trosclairs decision to leave coaching in Louisiana came reluctantly, after battling a cancer that he had never heard of until he learned he had it.

In spring 2014, he began to experience dizzy spells and fatigue. His blood pressure rose and his kidneys began to fail. The diagnosis was multiple myeloma, which begins in the bone marrow and limits the bodys ability to fight off infections, weakens bones, reduces kidney function and lowers a persons red blood cell count.

Trosclair began chemotherapy and taking a corticosteroid called Decadron, which left him intensely focused, insatiably hungry and agitated from extreme insomnia followed by bouts of crashing. He recalls his oncologist at the M.D. Anderson Cancer Center in Houston saying that he might lose his job in such a severe state. He jokingly replied, They already think Im crazy, so theyll give me a pass.

He asked one of his assistant coaches to remain vigilant in case his temper flared. Some days he felt 20 years old, he told a Louisiana reporter. Other days he felt 100. Still, Trosclair coached every game in the 2014 football season. In early 2015, he underwent a stem cell transplant. His own blood-making stem cells were harvested, frozen, then reintroduced after chemotherapy to produce new, healthy blood cells. He spent six weeks in Houston for the treatment and recovery.

People in Eunice raised some money and it was a big help, Trosclair said.

Months later, though, a mix-up over blood thinners during the 2015 football season led to a blood clot in his left leg and forced him into intensive care at a hospital in Lafayette, La. His left foot swelled to three times its normal size. Three surgeries were required, causing him to miss his only game in 25 seasons. Trosclair spoke to his team beforehand by phone, saying, I love you. Go out and play.

Irma Trosclair, his wife and the superintendent of schools in Lafayette Parish, one of Louisianas largest school districts, still keeps a video of the bedside pep talk.

When I saw him doing that, with all those tubes he had going, I knew that coaching wasnt just work, she said. It was what was going to pull him through.

In 2018, Eunice High unexpectedly reached the Class 3A state championship game and prevailed, 59-47, with Trosclairs Wing-T offense, an intricate symphony of misdirection and strategic passing. After a quarter century at the school and five seasons of fighting cancer, he claimed his biggest football victory. Trosclair told a television interviewer, It was like the universe opened its doors and said, here you go, heres a gift for you.

The high school and its football team confirm that Eunice still measures up, even as its population and student enrollment continue to shrink and a third of its 9,800 residents live in poverty. It is the only traditional public high school in St. Landry Parish to carry an A-rating of academic performance from the state and has maintained its diversity a half century after desegregation.

When you think of Eunice High, you think of Coach Trosclair, said the principal, Mitch Fontenot. Everybody looks up to him. He has a real calming effect. Its a big loss.

Sixteen starters were to return for the 2020 season. Another deep playoff run seemed possible. But the coronavirus shuttered Louisiana schools in March and the state became a hot spot. Trosclair no longer felt he could protect himself and manage his team safely at the same time. Retirement began to seem inevitable.

On June 18, Trosclair saw Dr. Donna M. Weber, his oncologist at M.D. Anderson, who wrote in a letter that he was at particular risk of infection during the pandemic and that she advised him not to return to work.

Irma Trosclair said, He needed his doctor to tell him he absolutely had no other option. I think hes very much at peace with it.

There has been sobering validation of Trosclairs decision. The athletic director of an area high school also retired with multiple myeloma. The father of one of Trosclairs former players died of Covid-19. Trosclairs replacement at Eunice High, interim coach Andre Vige, 41, tested positive, along with two Eunice High players, one of whom was hospitalized. All have recovered. Two teenage brothers in the area, the youngest a football player, also contracted the virus. The elder brother died at age 19.

Its possible for young people to die, Trosclair said. Thats the scary thing.

He spent the summer playing golf, taking 6 a.m. walks around the Eunice High track and lifting weights at the school when no one was around. He takes Revlimid, a maintenance medication, three weeks of every four. And while fatigue and muscle spasms persist, acupuncture has helped relieve the burning feeling in his feet. His red blood cell count and other markers are encouraging. Still, he has avoided large gatherings.

When the Eunice city council honored him, his wife went in his place. His grandchildren have not visited since March. When his youngest son, Trenon, 26, got married in June, Trosclair sat in an isolated section of the church, then left through a side door and skipped the reception.

Im really sad right now, he texted his wife.

Louisianas delayed high school football season is set to begin on Oct. 1. Trosclair would like to remain involved with the team in some manner. He has studied plays at the dining room table with Trenon, the teams secondary coach. Perhaps he will help with game planning. He would like to attend games, if he can stand away from everyone, but his wife is skeptical. She has another idea.

Hopefully theyll let me keep my same parking spot, Irma Trosclair said. Then we can watch the whole game from my vehicle. Surely theyll grant that for Coach.

Gillian Brassil contributed reporting. Sheelagh McNeill and Susan Beachy contributed research.

Read the original post:
The Pandemic Is Chasing Aging Coaches From the Field - The New York Times

Bone Marrow Stem Cells Comments Off on The Pandemic Is Chasing Aging Coaches From the Field – The New York Times | September 18th, 2020

Life expectancy for people with sickle cell disease appears to be declining, and the same systemic racism being protested around the nation could be at least partly responsible, a local expert says.

If you compare other orphan diseases, like cystic fibrosis or hemophilia, which have less cases than sickle cell, and then compare funding and research, its a night-and-day difference, said Dr. Alan R. Anderson, director of Prisma Health Upstates Comprehensive Sickle Cell Disease Program.

The U.S. Food and Drug Administration defines an orphan disease as a condition that affects fewer than 200,000 people nationwide.

That directly goes along with this same prejudice, racial disparities that we see in our political-social landscape, he said. Its about time we recognize this is a serious problem.

Anderson points to a National Institutes of Health study that concluded that life expectancy dropped from 42 for men and 48 for women in the early 1990s to 42 for women and 38 for men in 2005 even as life expectancy increased for people with other chronic conditions.

And a Sept. 1 New England Journal of Medicine article reports that while cystic fibrosis affects a third fewer than sickle cell, it receives seven to 11 times the funding. The authors added that the development of disease-modifying therapies has stagnated because of inadequate research funding, attributable at least in part to structural racism.

Sickle cell disease (SCD) is a genetic disorder of the red blood cells that primarily affects African Americans, though people from Hispanic, southern European, Middle Eastern, southern Asia, or Asian Indian backgrounds can also get the disease. Both parents must carry the genes for their child to get the disease.

While healthy cells are round, in people with SCD they resemble a sickle, or C shape, and are also hard and sticky, clogging the flow of blood through the vessels, according to the U.S. Centers for Disease Control and Prevention. Symptoms include pain, infections and stroke, and typically begin when a child is around 5 months old.

Treatments include medicines that can reduce complications and extend life, the agency reports, but the only cure is a risky bone marrow or stem cell transplant from a close match, like a brother or sister.

The state Department of Health and Environmental Control says that despite improvements in treatments, SCD remains a life-limiting disease with multi-organ complications that reduces the quality of life of impacted individuals especially as the person ages.

DHEC also reports that SCD has suffered from decades of poor disease awareness and lack of funding compared to other inherited disorders.

Historically, Anderson said, while children are cared for via Medicaid, adults often lack insurance so they have no medical home. And along with the funding disparity, there is a lack of training for medical professionals about SCD.

This is not rocket science, he said. If you focus on sickle cell disease like you do on diabetes and other chronic diseases, we will see reductions in acute care needs that will ultimately manifest in life expectancy.

DHEC has an SCD plan that calls for improving access to care, sustainable funding and increasing the educational awareness of medical professionals about SCD.

Its going to take more research and more advocacy and, I believe, policy changes, said the Rev. Sean Dogan of Long Branch Baptist Church in Greenville. We need that same momentum for SCD as well.

Anderson said that Prismas program has stepped up preventive health strategies and treatments for people of all ages while reducing ER visits and hospitalizations by about 50%, which will hopefully increase life expectancy.

Last year, it launched Camp Crescent to provide SCD patients and their families a respite from the disease. But the pandemic prevented that this year.

So organizers are holding a block party from 4-6 p.m. on Sept. 19 where people can safely gather for some fun and to raise awareness, said Dogan.

Its going to be an exciting event to raise awareness [and] celebrate those who have SCD and their caregivers, he said. The more awareness the community has, the more support it will give. And our community is a very generous community.

Modeled on the drive-by birthday parties so popular during the pandemic, it will feature patients and their families driving by the entrance of Prismas Cancer Center on Faris Road, he said. There, theyll find encouragement, well wishes and fun activities like quizzes with prizes, he said.

Meanwhile, on Sunday, blood drives to benefit patients will be held in the area, including one at Long Branch from 10 a.m. to 2 p.m., he said.

To learn more about the event, go to http://events.r20.constantcontact.com/register/event?oeidk=a07eh9btc8wd9af19f2&llr=76g5y7tab or https://www.ghschildrens.org/programs/camp-crescent/.

While the exact number of people with SCD is unknown, its estimated they number about 100,000 nationwide.

South Carolina doesnt track SCD numbers, but between 1991 and 2017, 1,884 infants were born with it, DHEC said. Another 56,607 were born with sickle cell trait, which means they dont have symptoms but can pass the gene on to their children.

Read the original:
Block party planned to raise awareness of sickle cell disease - Greenville Journal

Bone Marrow Stem Cells Comments Off on Block party planned to raise awareness of sickle cell disease – Greenville Journal | September 18th, 2020

After Graham Weston caught the coronavirus from his son, who hadnt shown any symptoms, the San Antonio tech entrepreneur realized that the role of silent spreaders demanded more attention.

He and other prominent philanthropic leaders in the city formed a new nonprofit with the express purpose of screening hundreds and eventually thousands of people to identify who is infected and asymptomatic and keep them from unknowingly spreading the virus.

The larger goal is even more ambitious: deliver an effective way of supporting societys recovery from the pandemic.

We can never really suppress the virus and give people the confidence to go back (to school or work) when we have silent spreaders walking through our population, said Weston, founder of the 80 | 20 Foundation and former CEO and chairman of Rackspace Technology.

The nonprofit, called Community Labs, has adopted a new approach to testing that focuses on micro populations in shared places, such as area schools and businesses.

It is using an existing test developed by Thermo Fisher Scientific. The polymerase chain reaction, or PCR, test relies on a sample taken from the front of the nostril easier on the person getting tested. Results will be available within 24 hours, far faster than many providers of coronavirus tests, the nonprofits leaders said Thursday during their announcement of the initiative.

The nonprofit will pilot the testing effort in the Somerset Independent School District. It has the capacity to process 600 tests a day and aims to scale up to 12,000 tests a day by November, with the goal of lowering the price to $35 per test.

Community Labs is working with BioBridge Global, which houses the nonprofit and conducts the testing in collaboration with UT Health San Antonio. BioBridge, which operates San Antonios blood bank, owns its own lab off Interstate 10 near Vance Jackson on the West Side.

Experts estimate that up to half of people who contract the coronavirus may display no symptoms, said bank executive J. Bruce Bugg Jr., chairman and trustee of the Tobin Endowment and co-founder of Community Labs. While hospitals have widely screened patients for the coronavirus when they are scheduled for surgery, federal and local health officials have largely prioritized testing people with symptoms.

On ExpressNews.com: New nonprofit aims to improve COVID-19 testing

Its an approach that has persisted since early in the pandemic, when testing for the coronavirus was severely limited by regulatory, processing and supply chain bottlenecks. Health departments, including the San Antonio Metropolitan Health District, initially focused their efforts on people who were severely ill, those with classic symptoms and front-line workers.

Metro Health briefly tested asymptomatic people in the community earlier this year but halted the effort when a surge of cases over the summer caused demand for testing to skyrocket.

While testing those with symptoms may help diagnose people with COVID-19, it does little to halt chains of transmission that stem from asymptomatic carriers. To fill that testing gap, Community Labs is taking the exact opposite approach, Bugg said.

He said the goal is to create a strong testing model that screens for asymptomatic carriers and that can be replicated and applied in cities across the state.

Community Labs approach hinges on quick turnaround times, which are not typical with the traditional testing. Waiting a week for results would render the value of testing asymptomatic people moot, Weston said, as they wont know to isolate themselves and already could have spread the virus to others by the time they learn they are infected.

Dr. Rachel Beddard, chief medical officer of BioBridge, said the company already conducts fast, high-volume testing for communicable diseases on blood products collected by the South Texas Blood and Tissue Center and on tissue, bone marrow and stem cells gathered by GenCure, another subsidiary.

Earlier this year, federal regulators granted an emergency use authorization for the coronavirus test that BioBridge is using.

On ExpressNews.com: San Antonio students are back in classrooms very different classrooms

Somerset ISD, a seven-school system in rural Southwest Bexar County, was selected as a demonstration site after its superintendent, Saul Hinojosa, agreed to participate.

With about 40 percent of all students having returned to school for in-person learning, the district will begin testing students and staff Wednesday, starting with students involved in extracurricular activities, all high school staff and all nurses and police officers. Only students whose parents sign a consent form will be tested at school, Hinojosa said.

The goal is to test as many students as possible so they, their parents and staff feel comfortable returning to school. If everything goes according to plan and enough students agree to get tested, Hinojosa said, the entire district could be back learning face to face earlier than expected.

We need students in the classroom because thats where they learn best, and we hope that this strategy will lessen the concern on parents, along with the anxiety, to where they feel confident that the school campus is a safe environment for the kids, he said.

Unlike the deep nasal swabs that have been used to collect samples for many coronavirus tests, the test used by Community Labs uses a sample thats simpler and far less invasive to collect. Participants rub a small Q-tip inside each nostril for five seconds before dropping it into a test tube.

Community Labs was co-founded by Weston, Bugg and J. Tullos Wells, managing director of the Kronkosky Charitable Foundation. Weston is serving as chairman, while Bugg and Wells are vice chairmen.

The Kronkosky and 80 | 20 foundations and the Tobin Endowment have contributed a combined $2.5 million to start the nonprofit.

Lauren Caruba covers health care and medicine in the San Antonio and Bexar County area. To read more from Lauren, become a subscriber. lcaruba@express-news.net | Twitter: @LaurenCaruba

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Silent spreaders of the coronavirus are the target of a new testing venture in San Antonio - San Antonio Express-News

Bone Marrow Stem Cells Comments Off on Silent spreaders of the coronavirus are the target of a new testing venture in San Antonio – San Antonio Express-News | September 18th, 2020

It is September of a presidential election year, with a divided government and a deeply polarized electorate. Many congressional watchers would tell you that absolutely nothing could pass in this environment. Earlier this month, however, in defiance of the naysayers and in the spirit of all too rare bipartisanship, the House Energy and Commerce Committee overwhelmingly voted to reauthorize the C.W. Bill Young Cell Transplantation Program (the Program).

We must extend this demonstration of bipartisanship and willingness to work together to save American lives to the full House and the Senate and ensure that the Program is reauthorized before it expires at the end of September.

For 30 years, Congress has authorized and re-authorized the Program, which provides access to life-saving bone marrow, peripheral blood stem cell and cord blood transplants for patients living with one of the more than 70 blood cancers or blood disorders for which transplant is the only curative option.

The Program was first established through a partnership with the Navy in 1986, transferred to the NIH for oversight the following year, then authorized by Congress in 1994 and has been reauthorized in 1998, 2005, 2010, and 2015.

During those 30 years, the National Marrow Donor Program/Be The Match (NMDP) has facilitated more than 100,000 lifesaving and life-extending transplants.

While the Program enjoys broad bipartisan and bicameral support, as it has during every other reauthorization, it is still in jeopardy which is why we strongly urge Congress to act swiftly to protect the Program and the patients who rely on it.

Because of its unassailable mission, because of its great successes over three decades, and because the Program is relied upon by more patients than ever before, reauthorization of the national registry remains non-controversial.

Reauthorization was critical before the pandemic, but now because of the wild unpredictability of COVID-19, and its downstream impacts that create life-threatening risk to bone marrow transplant patients, it is even more urgent that Congress reauthorize the Program before adjourning for the election.

Thanks in large part to the national program status afforded to NMDP under the authorizing statue, we were:

These critical victories during the pandemic share two common, and extraordinarily important, threads. First, we would not have been able to secure these victories without NMDPs national program status. And, second, patients in the U.S. would have died had these things not happened.

While we have no way to predict exactly what the next emergencies will look like, we nevertheless know with certainty that they will happen. Based upon the unfathomable experience of the last six months, we know that the lynch pin to the solution will be our national program status.

This is exactly why reauthorization now is so critical.

No lapse in the Program means no lapse in our national program status. And that means no lapse in our ability to move mountains in our efforts to leave no patient without the transplant that they so desperately need.

The members of the House Energy & Commerce Committee proved that even in these most trying political times, Congress can come together and work across the aisle to save the lives of Americans in need. We hope the full House and the Senate will follow suit and act quickly to reauthorize the Program.

Brian Lindberg is the chief legal officer and chief policy officer for the National Marrow Donor Program/Be The Match.

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Full House and Senate should reauthorize the C.W. Bill Young Cell Transplantation Program | TheHill - The Hill

Bone Marrow Stem Cells Comments Off on Full House and Senate should reauthorize the C.W. Bill Young Cell Transplantation Program | TheHill – The Hill | September 16th, 2020

Differences in biological sex can dictate lifelong disease patterns, says a new study by Michigan State University researchers that links connections between specific hormones present before and after birth with immune response and lifelong immunological disease development.

Published in the most recent edition of the Proceedings of the National Academy of Sciences, the study answers questions about why females are at increased risk for common diseases that involve or target the immune system like asthma, allergies, migraines and irritable bowel syndrome. The findings by Adam Moeser, Emily Mackey and Cynthia Jordan also open the door for new therapies and preventatives.

This research shows that its our perinatal hormones, not our adult sex hormones, that have a greater influence on our risk of developing mast cell-associated disorders throughout the lifespan, says Moeser, Matilda R. Wilson Endowed Chair, professor in the Department of Large Animal Clinical Sciences and the studys principle investigator. A better understanding of how perinatal sex hormones shape lifelong mast cell activity could lead to sex-specific preventatives and therapies for mast cell-associated diseases."

Mast cells are white blood cells that play beneficial roles in the body. They orchestrate the first line of defense against infections and toxin exposure and play an important role in wound healing, according to the study, Perinatal Androgens Organize Sex Differences in Mast Cells and Attenuate Anaphylaxis Severity into Adulthood.

However, when mast cells become overreactive, they can initiate chronic inflammatory diseases and, in certain cases, death. Moesersprior research linked psychological stress to a specific mast cell receptor and overreactive immune responses.

Moeser also previously discovered sex differences in mast cells.Female mast cells store and release more inflammatory substanceslike proteases, histamine and serotonin, compared with males. Thus, female mast cells are more likely than male mast cells to kick-start aggressive immune responses. While this may offer females the upper hand in surviving infections, it also can put females at higher risk for inflammatory and autoimmune diseases.

IBS is an example of this, says Mackey, whose doctoral research is part of this new publication.

While approximately 25% of the U.S. population is affected by IBS,women are up to four times more likelyto develop this disease than men.

Moeser, Mackey and Jordans latest research explains why these sex-biased disease patterns are observed in both adults and prepubertal children. They found that lower levels of serum histamine and less-severe anaphylactic responses occur in males because of their naturally higher levels of perinatal androgens, which are specific sex hormones present shortly before and after birth.

Mast cells are created from stem cells in our bone marrow, Moeser said. High levels of perinatal androgens program the mast cell stem cells to house and release lower levels of inflammatory substances, resulting in a significantly reduced severity of anaphylactic responses in male newborns and adults.

We then confirmed that the androgens played a role by studying males who lack functional androgen receptors, says Jordan, professor of Neuroscience and an expert in thebiology of sex differences.

While high perinatal androgen levels are specific to males, the researchers found that while in utero, females exposed to male levels of perinatal androgens develop mast cells that behave more like those of males.

For these females, exposure to the perinatal androgens reduced their histamine levels and they also exhibited less-severe anaphylactic responses as adults, says Mackey, who is currently a veterinary medical student at North Carolina State University.

In addition to paving the way for improved and potentially novel therapies for sex-biased immunological and other diseases, future research based will help researchers understand how physiological and environmental factors that occur early in life can shape lifetime disease risk, particularly mast cell-mediated disease patterns.

While biological sex and adult sex hormones are known to have a major influence on immunological diseases between the sexes, were learning that the hormones that we are exposed to in utero may play a larger role in determining sex differences in mast cell-associated disease risk, both as adults and as children, Moeser said.

Reference: Mackey E, Thelen KM, Bali V, et al. Perinatal androgens organize sex differences in mast cells and attenuate anaphylaxis severity into adulthood. Proc Natl Acad Sci USA. Published online September 11, 2020:201915075. doi:10.1073/pnas.1915075117.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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How the Hormones You're Born With Influence Disease Risk - Technology Networks

Bone Marrow Stem Cells Comments Off on How the Hormones You’re Born With Influence Disease Risk – Technology Networks | September 16th, 2020

The parents of a cancer-stricken toddler have launched a desperate search for a bone marrow donor to step forward and save their daughters life.

Three-year-old Adeline Davidson, from Alness, suffers with a rare form of blood cancer which affects only one in every 250,000 children.

Her only hope of survival is finding a suitable bone marrow donor.

Earlier this year her parents Steph, 26, and Jordan, 28, were ecstatic to have found two viable donors taking them one step closer to saving the happy go lucky youngster.

However, their world came crumbling down on Monday when consultants told them that both were no longer viable and there were no matching donors left on the register.

The heartbroken mum said the news has left them at a loss and right back to where they were almost two years ago.

She said: Its absolutely devastating.

We got a phone call and I thought it was a date for a transplant, so this was the last thing I was expecting.

I didnt actually process anything she said until I was off the phone and I just thought what on earth does that even mean for us now?

It felt like someone had just stabbed me in the gut. It was horrendous.

We have literally no idea how long we are going to be waiting for.

I cant put into words how heartbroken we are after finding out Adeline no longer has a donor available and we are back

Posted by Steph Davidson onMonday, 14 September 2020

Sharing the heartbreaking news on social media, the 26-year-old mother of-three said she couldnt explain the pain she felt daily knowing Adeline wasnt experiencing life as a normal healthy three-year-old.

She added: We were ecstatic when we first found out there even was a match because its a long process and a long wait.

But to have that taken away from you and to be left with nothing after all this time, I honestly cant explain it.

Adeline is so happy and a part of me is happy for that, but also it saddens me because I just think she has no idea what she is missing out on.

Mrs Davidson says for Adeline, everyday health problems such as a common cold, virus or sickness bug could be fatal.

If her bone marrow failure is left, it could develop leading her to become unwell and unstable or develop conditions such as leukaemia if her body begins producing abnormal cells.

The Ross-shire family is now pleading with individuals to sign up to become a stem cell or bone marrow donor to help save terminally ill children such as Adeline.

Mrs Davidson said: The only thing that we can do is try and search for this match.

Only 0.04% of the population are on the register so the facts are against us but I just want more hope.

I just really hope that people are convinced to sign up and share the word elsewhere.

It means the world when people say I have signed up because of your story.

However, many individuals that are signing up, they possibly cant be the match for Adeline but they possibly could be for someone else. There is so many people like Adeline that are waiting for this.

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Highland family issue urgent plea to help find life-saving bone marrow donor for three-year-old daughter - Press and Journal

Bone Marrow Stem Cells Comments Off on Highland family issue urgent plea to help find life-saving bone marrow donor for three-year-old daughter – Press and Journal | September 16th, 2020

Hematopoietic stem cells are young or immature blood cells found to be living in bone marrow. These blood cells on mature in bone marrow and only a small number of these cells get to enter blood stream. These cells that enter blood stream are called as peripheral blood stems cells. Hematopoietic stem cells transplantation is replacement of absent, diseased or damaged hematopoietic stem cells due to chemotherapy or radiation, with healthy hematopoietic stem cells. Over last 30 years hematopoietic stem cells transplantation market seen rapid expansion and constant expansion with lifesaving technological advances. Hematopoietic stem cells transplantation is also known blood and marrow transplantation which brings about reestablishment of the patients immune and medullary function while treating varied range of about 70 hematological and non-hematological disorders. In general hematopoietic stem cells transplantation is used in treatment of hereditary, oncological, immunological and malignant and non-malignant hematological diseases.

There are two types of peripheral blood stem cell transplants mainly autologous and allogeneic transplantation. In autologous transplants patients own hematopoietic stem cells are harvested or removed before the high-dose treatment that might destroy the patients hematopoietic stem cells. While in allogeneic transplants stem cells are obtained from a tissue type of matched or mismatched donor. Hematopoietic stem cells are harvested from blood or bone marrow and is then frozen to use later. Depending upon the source of hematopoietic stem cells, worldwide there are three types of hematopoietic stem cells transplants namely bone marrow transplant (BMT), peripheral blood stem cell transplant and cord blood transplant. Major drivers in the hematopoietic stem cells transplantation market are establishment of strong and well developed network of hematopoietic stem cells transplantation organizations having global reach and presence has recognized NGO named Worldwide Network for Blood and Marrow Transplantation Group (WBMT) in official relation with World Health Organization (WHO) and rapid increase in number of transplants. Major restraints in hematopoietic stem cells transplantation market is high cost of transplantation and lack of funding for WBMT and other organizations such as regional, national and donor.

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The global market for Hematopoietic stem cells transplantation market is segmented on basis of transplant type, application, disease indication, end user and geography:

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Based on transplantation type, hematopoietic stem cells transplantation market is segmented into allogeneic and autologous. Hematopoietic stem cells transplantation market is also segmented by application type into bone marrow transplant (BMT), peripheral blood stem cell transplant and cord blood transplant. The market for hematopoietic stem cells transplantation is majorly driven by bone marrow transplant (BMT) segment. Based on end user hematopoietic stem cells transplantation market is segmented into hospitals and specialty centers. Peripheral blood stem cell transplant type holds the largest market for hematopoietic stem cells transplantation. Hematopoietic stem cells transplantation market is further segmented by disease indication into three main categories i.e. lymphoproliferative disorders, leukemia, and non-malignant disorders. Segment lymphoproliferative disorder holds largest share amongst the three in Hematopoietic stem cells transplantation market. On the basis of regional presence, global hematopoietic stem cells transplantation market is segmented into five key regions viz. North America, Latin America, Europe, Asia Pacific, and Middle East & Africa. Europe leads the global hematopoietic stem cells transplantation market followed by U.S. due to easy technological applications, funding and high income populations. Other reasons for rise in hematopoietic stem cells transplantation market is high prevalence of lymphoproliferative disorders and leukemia; demand for better treatment options; and easy accessibility and acceptance of population to new technological advances. Transplantation rates in high income countries are increasing at a greater extent but continued rise is also seen in low income countries and expected to rise more. Hematopoietic stem cells transplantation market will have its potential in near future as being a perfect alternative to traditional system in many congenital and acquired hematopoietic disorders management. While India, China and Japan will be emerging as potential markets. An excellent and long term alternative to relief by side effects of chemotherapy, radiotherapy and immune-sensitive malignancies is another driver for hematopoietic stem cells transplantation market. The key players in global hematopoietic stem cells transplantation market are Lonza, Escape Therapeutics, Cesca Therapeutics Inc., Regen BioPharma, Inc., Invitrx Inc, StemGenex, Lion Biotechnologies, Inc., CellGenix GmbH, Actinium Pharmaceuticals, Inc., Pluristem, Kite Pharma, Novartis AG.You Can Request for TOC Here @https://www.persistencemarketresearch.com/toc/14563

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Hematopoietic Stem Cells Transplantation Market to Witness a Substantiation between 2017 and 2025 - Scientect

Bone Marrow Stem Cells Comments Off on Hematopoietic Stem Cells Transplantation Market to Witness a Substantiation between 2017 and 2025 – Scientect | September 16th, 2020

NEW YORK, Sept. 15, 2020 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that its lead product candidate remestemcel-L has been selected as the winner of the Fierce Innovation Awards - Life Sciences Edition 2020 for Biotech Innovation.The Fierce Innovation Awards is a peer-reviewed program from the publisher ofFierceBiotech and FiercePharma.

Mesoblast Chief Executive Dr Silviu Itescu stated: This important award is recognition of Mesoblasts leadership as an innovator in the cell therapy industry, and of the potential for remestemcel-L to profoundly impact the lives of children suffering with steroid-refractory acute graft versus host disease (SR-aGVHD).

Remestemcel-L is under priority review by the United States Food and Drug Administration (FDA) for pediatric SR-aGVHD and, if approved, product launch in the United States is expected in 2020. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of September 30, 2020.

Remestemcel-L is an investigational therapy comprising culture-expanded mesenchymal stem cells derived from the bone marrow of an unrelated donor. It is thought to have immunomodulatory properties to counteract the cytokine storms that are implicated in various inflammatory conditions by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.

Given the extensive inflammatory response in COVID-19 infection, remestemcel-L is also being evaluated in a randomized, controlled Phase 3 trial in up to 300 ventilator-dependent adults with moderate to severe acute respiratory distress syndrome (ARDS), the primary cause of mortality in COVID-19 patients. The trial aims to confirm results from a pilot study at New Yorks Mt Sinai hospital which showed that nine of 12 patients (75%) were successfully discharged from hospital a median of 10 days after receiving two intravenous doses of remestemcel-L within five days.The trials independent Data Safety Monitoring Board (DSMB) recently completed an interim analysis of the trials first 30% enrolled patients and recommended that the trial should continue as planned after reviewing all safety data and results for the trials primary endpoint of all-cause mortality within 30 days of randomization.The DSMB will perform a second interim analysis when 45% of the enrollment target has completed 30 days of follow-up. About Fierce Innovation Awards Life Sciences Edition 2020These awards highlight companies that demonstrate innovative solutions, technologies, and services that have the potential to make the greatest impact for biotech and pharma companies.The evaluation criteria are effectiveness, technical innovation, competitive advantage, financial impact, and true innovation.The awards programs applications were reviewed by a panel of executives from majorbiotech and pharmacompanies includingAstellas, Accenture, AstraZeneca, Angiocrine Bioscience, Biotech Research Group, NIHR Clinical Research Network, Medidata Solutions and PPD.

About MesoblastMesoblast Limited (Nasdaq:MESO; ASX:MSB) is a world leader in developing allogeneic (off-the-shelf) cellular medicines. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of commercial products and late-stage product candidates. Mesoblast has a strong and extensive global intellectual property (IP) portfolio with protection extending through to at least 2040 in all major markets. The Companys proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.

Mesoblasts Biologics License Application to seek approval of its product candidate RYONCIL (remestemcel-L) for pediatric steroid-refractory acute graft versus host disease has been accepted for priority review by the United States Food and Drug Administration (FDA), and if approved, product launch in the United States is expected in 2020. Remestemcel-L is also being developed for other inflammatory diseases in children and adults including moderate to severe acute respiratory distress syndrome (ARDS). Mesoblast is completing Phase 3 trials for its product candidates for advanced heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblasts licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.

Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see http://www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast

Forward-Looking StatementsThis announcement includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward-looking statements include, but are not limited to, statements about: the timing, progress and results of Mesoblasts preclinical and clinical studies; Mesoblasts ability to advance product candidates into, enroll and successfully complete, clinical studies; the timing or likelihood of regulatory filings and approvals; and the pricing and reimbursement of Mesoblasts product candidates, if approved; Mesoblasts ability to establish and maintain intellectual property on its product candidates and Mesoblasts ability to successfully defend these in cases of alleged infringement. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblasts actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

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Mesoblast Wins 2020 Fierce Biotech Innovation of the Year Award for remestemcel-L - GlobeNewswire

Bone Marrow Stem Cells Comments Off on Mesoblast Wins 2020 Fierce Biotech Innovation of the Year Award for remestemcel-L – GlobeNewswire | September 16th, 2020