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HLA-Mismatched Unrelated Donor Bone Marrow Transplantation With Posttransplant Cyclophosphamide


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In a National Marrow Donor Program–sponsored phase II trial reported in the Journal of Clinical Oncology, Shaw et al found that a strategy of bone marrow hematopoietic cell transplant (HCT) from mismatched unrelated donors using posttransplant cyclophosphamide in patients with hematologic malignancies was feasible and effective in a population containing a high proportion of racial/ethnic minorities.

As noted by the investigators, despite the fact that unrelated donor registries contain more than 38 million volunteers, 25% to 80% of U.S. patients lack an HLA-matched unrelated donor, with patients from racial or ethnic minorities being disproportionately disadvantaged.

Our prospective study demonstrates the feasibility and effectiveness of HCT with a mismatched unrelated donor in the setting of [posttransplant] cyclophosphamide. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.
— Shaw et al

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Study Details

The study included 80 patients enrolled at 11 U.S. transplant centers between December 2016 and March 2019. After myeloablative conditioning (n = 40) or reduced-intensity conditioning (n = 40), patients underwent transplantation and received posttransplant cyclophosphamide on posttransplant days 3 and 4 and started sirolimus and mycophenolate mofetil on day 5. Overall, 39% of donor-recipient pairs were matched for four to six of eight HLA alleles, and 48% of patients were from racial/ethnic minority groups. The primary endpoint was 1-year overall survival, with the endpoint considered met if the rate were ≥ 65%.

Key Findings

Overall survival at 1 year was 76% (90% confidence interval [CI] = 67.3%–83.3%) among all patients, including 72% (90% CI = 59.9%­–83.1%) in the myeloablative conditioning cohort and 79% (90% CI = 66.9%–88.8%) in the reduced-intensity conditioning cohort. Rates were 75% (90% CI = 63.4%–84.3%) among patients matched for seven of eight HLA alleles and 77% (90% CI = 64.1%–88.4%) among those matched for four to six of eight alleles.

Primary graft failure was not observed in the myeloablative conditioning cohort and occurred in 7.5% of the reduced-intensity conditioning cohort.

Acute graft-vs-host disease of grade 2 to 4 and grade 3 to 4 at day 100 was observed in 43% and 18% of the myeloablative conditioning cohort and in 33% and 0% of the reduced-intensity conditioning cohort. Chronic graft-vs-host disease was observed in 36% of the myeloablative conditioning cohort and 18% of the reduced-intensity conditioning cohort.

Nonrelapse mortality and 1-year relapse rates were 8% and 30% in the myeloablative conditioning cohort and 10% and 23% in the reduced-intensity conditioning cohort.

No significant difference in 1-year overall survival (P = .761) was observed in multivariate analysis including the total study group and three cohorts of contemporary registry controls, consisting of patients receiving mismatched unrelated donor peripheral blood stem cell grafts (n = 143) or mismatched related donor recipients receiving bone marrow grafts (n  = 398) or peripheral blood stem cell grafts (n  = 1,191).

The investigators concluded, “Our prospective study demonstrates the feasibility and effectiveness of HCT with a mismatched unrelated donor in the setting of [posttransplant] cyclophosphamide. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.”

Bronwen E. Shaw, MD, PhD, of CIBMTR/Froedtert & the Medical College of Wisconsin, Milwaukee, is the corresponding author for the Journal of Clinical Oncology article.

Dislcosure: The study was supported by The National Marrow Donor Program/Be The Match, the Be The Match Foundation, Center for International Blood and Marrow Transplant Research (CIBMTR), and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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