Survival Benefit of GVHD in MDS Is Limited to Specific Patient Subgroup – Cancer Therapy Advisor

By daniellenierenberg

Development of limited, chronic graft-vs-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) was associated with a survival benefit for patients with high-risk myelodysplastic syndrome (MDS), according to results of a retrospective study published in Clinical Cancer Research.1

MDS is a heterogeneous group of clonal hematopoietic stem cell disorders characterized by an inadequate production of normal, mature blood cells in bone marrow.

At the present time, the only curative treatment for patients with MDS is allogeneic HSCT. Although risks associated with this approach include posttransplant relapse, as well as the development of acute and/or chronic GVHD, previous findings from studies of patients with acute leukemia treated with allogeneic HSCT have shown potent graft-vs-tumor effects manifesting as lower mortality in those patients who subsequently experienced chronic GVHD.

The clinical data used in this study were collected from more than 300 HSCT centers throughout Japan by the Japanese Data Center for Hematopoietic Cell Transplantation.

MDS was characterized as low- or high-risk disease according to the

French-American-British or World Health Organization classification schemes, depending on the year of diagnosis.2,3 Consensus criteria were used to assign GVHD severity and distinguish acute and chronic forms of the condition.

Study inclusion criteria dictated patients should be aged 16 through 70 years, had received first allogeneic HSCT between 2001 and 2017, had achieved neutrophil engraftment, and had a follow-up period of over 60 days.

Of the 3119 patients included in this study, 1193 and 1926 were classified as having low- and high-risk disease, respectively. In the overall group, the median patient age was 54 years, more than 90% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, and 85% were diagnosed with de novo disease.

At a median follow-up of 55 months, rates of 5-year overall survival (OS) were 63% and 48% for those with low- and high-risk disease, respectively (P <.001). The cumulative incidence of posttransplantation relapse at 5 years was approximately twice as high for those with high-risk disease (29%) compared with those with low-risk disease (15%; P <.001), although the cumulative incidence of nonrelapse mortality was similar in the 2 groups: 25% (low-risk disease) and 27% (high-risk disease; P =.338).

Multivariate analyses accounting for all confounding variables performed to evaluate these transplant outcomes in patient subgroups defined according to disease risk, as well the severity of GVHD and whether it was classified as acute or chronic, revealed the following:

In summarizing the results of this study, the study authors emphasized that these data demonstrated a survival benet of the graft-versus-MDS effect is present only in high-risk MDS patients with limited chronic GVHD.1

Authors of an accompanying editorial noted that in recent years, the mutational spectrum in MDS has become more associated with clinical phenotype and prognosis, and selection of a patient with MDS for HSCT has begun to incorporate the mutational landscape of the patients disease. Thus, one will have to be cautious in extrapolating the current data to ongoing and future trials, which have begun to incorporate molecular information.4

References

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Survival Benefit of GVHD in MDS Is Limited to Specific Patient Subgroup - Cancer Therapy Advisor

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