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Study results indicate MUDs may be preferred over haplo donors in certain indications

MUD HCT outcomes superior to haplo when both use RIC and PTCy prophylaxis for treatment of acute leukemia or myelodysplastic syndromes

August 2021

Key insights from the haplo HCT vs. MUD HCT with PTCy study

  • If available, matched unrelated donors should likely be prioritized over haploidentical donors.
  • 8/8 MUD HCT with PTCy-based GVHD prophylaxis resulted in superior overall survival and disease-free survival compared to haploidentical HCT with PTCy in the RIC setting for treatment of acute leukemia and myelodysplastic syndromes.
  • Patients who received RIC haplo HCT had higher graft failure, slower engraftment, more severe acute GVHD and higher non-relapse mortality.
  • Researchers found no differences in overall or disease-free survival in the MAC setting, but haplo HCT was associated with more severe acute GVHD and slower platelet engraftment.
  • Time from diagnosis to HCT did not differ by donor type.
  • CIBMTR® (Center for International Blood and Marrow Transplant Research®) observational study results published in Blood.

Study summary: Haplo HCT vs. MUD HCT with PTCy prophylaxis

The use of post-transplant cyclophosphamide (PTCy) as a graft-versus-host disease (GVHD) prophylaxis has led to a rise in haploidentical (haplo) hematopoietic cell transplantation (HCT) over the last decade. Previous studies demonstrated similar results between HLA matched unrelated donor (MUD) HCT and haplo HCT.

However, those studies were not apples-to-apples comparisons. In those studies, haplo patients received PTCy-based GVHD prophylaxis while MUD patients received traditional calcineurin inhibitor-based GVHD prophylaxis.

The CIBMTR Graft Sources Working Committee conducted an observational study in which haplo patients and MUD patients both received PTCy-based GVHD prophylaxis for treatment of acute leukemia and myelodysplastic syndromes. This offered for the first time in a CIBMTR working committee study a direct comparison between the two donor sources. The primary outcome was overall survival with secondary outcomes of relapse, disease-free survival, engraftment/graft failure, and acute and chronic GVHD.

The study population included:

  • Haplo PTCy: Reduced intensity conditioning (RIC)=1,211; myeloablative conditioning (MAC)=825
  • 8/8 MUD PTCy: RIC=187; MAC=97
  • ≥ 18 years old with AML, ALL or MDS

Haplo vs. MUD study results

In the RIC group, patients who received a MUD transplant had higher disease-free survival (55% vs. 41%) and overall survival (67% vs. 54%) than patients who received a haplo transplant.

In addition, RIC patients who received MUD HCT had:

  • Lower 2-year graft failure
  • Faster engraftment
  • Less severe acute GVHD
  • Lower non-relapse mortality

While there were no differences in overall or disease-free survival in the MAC cohort, haplo HCT was associated with:

  • Higher severe acute GVHD
  • Slower platelet engraftment

Follow up for the MAC cohort was 1 year compared to 2 years for the RIC cohort. Importantly, in both cohorts, there was no evidence that time to transplant from diagnosis when using a haploidentical donor was any faster than a MUD.

Haplo vs. MUD study conclusions and implications for clinical

Data from the study confirm the importance of HLA matching for allogeneic HCT. When using the same PTCy GVHD prophylaxis, MUD outcomes were superior to haplo. In addition, while there is a perception in the transplant community that haplo leads to a shorter treatment timeline, no studies have demonstrated this.

Therefore, physicians should still consider prioritizing a MUD over a haploidentical donor whenever one is available, particularly if the plan is to use PTCy for GVHD prophylaxis. This is especially true for patients receiving RIC for treatment of acute leukemia and myelodysplastic syndromes.

Further research into the use of PTCy in MUD and MRD HCT

The MUD cohort in this study was small as PTCy has not been commonly used in MUD transplants. The use of PTCy in 8/8 MUD transplants is the current subject of a Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trial, PROGRESS III.

The PROGRESS III trial is a randomized, phase III, multicenter study. Investigators will compare outcomes between standard GVHD prophylaxis tacrolimus/methotrexate (Tac/MTX) to PTCy/tacrolimus/ mycophenolate mofetil (PTCy/Tac/MMF) when using a matched related or unrelated donor.

The CIBMTR is a research collaboration between NMDP and the Medical College of Wisconsin. The BMT CTN is a collaborative effort of 20 Core Transplant Centers/Consortia, the CIBMTR, the NMDP and the Emmes Corporation.

Gooptu M, et al. Blood. 2021.