Allogenic HCT Using Younger, Unrelated Donors May Curb Relapse in MDS

NEW YORK (Reuters Health) – For patients with myelodysplastic syndrome (MDS), using younger human leukocyte antigen-matched unrelated donors (MUDs) for allogenic hematopoietic cell transplantation (allo-HCT) was associated with better outcomes than using older matched sibling donors (MSDs) in a retrospective study.

“MDS is a disease of older adults and if they have a matched sibling donor available, the donor is also likely to be older and have issues from aging,” Dr. Guru Subramanian Guru Murthy of the Medical College of Wisconsin in Milwaukee told Reuters Health by email. “When an older MSD and a younger MUD are available as options, clinicians wonder if one is a better donor than the other, and the usual choice is an MSD.”

Yet, the study found that younger MUDs were associated with “significantly lower risk of relapse and superior disease-free survival, suggesting this to be a potential way to minimize relapse of MDS after transplant,” he noted. “We suspect that possible favorable factors in younger MUDs – such as lesser incidence of clonal hematopoiesis of indeterminate potential, higher graft-versus-tumor effect – could have led to the lower incidence of relapse and better disease-free survival.”

As reported in JAMA Oncology, Dr. Murthy and colleagues assessed data from 1,761 MDS patients (median age, 65; 66%, men); 646 (37%) underwent allo-HCT with an older MSD and the rest, with a younger MUD.

In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio, 1.17); no significant between-group differences were seen in overall survival.

Further, allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62); lower nonrelapse mortality (HR, 0.76); lower acute graft-versus-host disease (GVHD; HR, 0.52); chronic GVHD (HR, 0.77); and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42).

The authors conclude, “These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.”

Dr. Asya Nina Varshavsky-Yanovsky, an assistant professor in the Department of Bone Marrow Transplant and Cellular Therapies at Fox Chase Cancer Center in Philadelphia, commented on the study in an email to Reuters Health.

“The study provides high quality data regarding relapse risk and non-relapse mortality and GVHD outcomes,” she said. “It is important to keep in mind that while relapse risk is clearly reduced with younger MUDs compared to older MSDs, overall survival was not significantly improved, and this is due to increased treatment-related mortality and GVHD rates with MUD.”

“Slightly more patients in the MUD cohort experienced negative effects of GVHD on quality of life, compared to the MSD cohort,” she noted. “In my opinion, the conclusions we learned from this important study should be applied individually to each patient, weighing the risks of increased treatment-related mortality and GVHD versus the risks of early relapse, considering disease risk and patient characteristics.”

“The study excluded patients who received GVHD prophylaxis with post-transplant (cyclophosphamide),” she added. “I do not think the results can be extrapolated to (those) patients, as GVHD and non-relapse mortality outcomes may be different in this population. Additional studies are needed to address the donor choice question in the context of post-transplant cyclophosphamide, which is now being increasingly used for MSD and MUD transplants.”

SOURCE: https://bit.ly/3FKH0NL JAMA Oncology, online January 13, 2022.

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