HLA-matching with PTCy: a reanalysis of a CIBMTR dataset with propensity score matching and donor age

Abstract

Blood or marrow transplantation (BMT) outcomes using haploidentical donors (Haplo) and post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GVHD) prophylaxis compare favorably to using HLA-matched donors with calcineurin inhibitor-based GVHD prophylaxis. A recent CIBMTR analysis of patients receiving homogenous PTCy-based prophylaxis found that, with reduced intensity conditioning, Haplo BMTs had worse outcomes than matched unrelated donor (MUD) BMTs. Due to significant differences in characteristics between the groups, we reanalyzed the dataset using propensity score matching and, additionally, added a donor age variable. MUD BMTs were matched to Haplo BMTs in a 1:5 ratio. After matching, no significant differences were found between groups across all measured baseline characteristics. Outcomes analyses demonstrated no significant differences in overall survival (HR of mortality with MUD vs Haplo [95% CI], 0.95[0.65-1.16], P=0.75), disease free survival (HR of relapse or death, 0.98[0.73-1.18], P=0.89), relapse rate (HR, 1.06[0.77-1.38], P=0.69), or non-relapse mortality (HR, 0.85[0.42-1.13], P=0.49) between the two groups. After stratification by conditioning intensity, MUD BMTs in the RIC cohort had a lower risk of NRM (HR, 0.56 [0.14-0.99], P=0.05), with no significant difference in other clinical outcomes. These results suggest that the effect of HLA matching on BMT outcomes with PTCy is less meaningful than previously reported and observed differences resulted in part from differences in donor age. Timely identification of a young, at least half-matched (related or unrelated) donor may be more important than finding a matched donor, if the latter leads to a substantial delay in BMT or use of an older donor.

Haploidentical Donor Blood or Marrow Transplantation for Myelodysplastic/Myeloproliferative Overlap Neoplasms: Results from a North American Collaboration

“…In the current era, the use of haploidentical donors in the broad scope of BMT has evolved signi cantly since the advent of posttransplantation cyclophosphamide (PTCy). [7][8][9][10] The role of haploidentical donors in MDS/MPN offers the potential advantage of available donors in a timely manner for an otherwise incurable malignancy. Additionally, nding a fully matched donor in the donor registry can be challenging for non-White patients due to the lower diversity of donors from these populations.…”

Comparable relapse incidence after unrelated allogeneic stem cell transplantation with post‐transplant cyclophosphamide versus conventional anti‐graft versus host disease prophylaxis in patients with acute myeloid leukemia: A study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…However, subsequent single-center and registrybased studies that assessed transplantation outcomes as per disease risk, demonstrated that Haplo-HSCT with PTCy outcomes including RI appeared comparable to those of HLA-matched transplants with No PTCy. 24,25,39 Yet the scenario may differ in the setting of UD-HSCT, which emphasizes the importance of our finding of a 2-year RI of 24.9% with PTCy-based anti-GVHD prophylaxis in AML patients undergoing UD-HSCT. The RI we observed in the PTCy cohort is very similar to the figures of 11%-39.1% observed in the previous studies that evaluated outcomes of UD-HSCT with PTCy including previous studies from our group.…”

“…[17][18][19] From a clinical point of view, GVHD (especially in its chronic form) correlates with RI and besides the actual occurrence of clinical relapse, it is almost the only read-out assay for the so-called GVL effect. 5,6,8,38,39 As PTCy anti-GVHD prophylaxis resulted in a significant reduction of GVHD and even more so of cGVHD, 14,15,24 there is further theoretic support to the notion that PTCy is attributed to the high RI observed post-Haplo-HCST with its administration. However, subsequent single-center and registrybased studies that assessed transplantation outcomes as per disease risk, demonstrated that Haplo-HSCT with PTCy outcomes including RI appeared comparable to those of HLA-matched transplants with No PTCy.…”

Recent advances in allogeneic transplantation for acute myeloid leukemia

“…It has allowed, because of its effectiveness and relative simplicity, the widespread use of this procedure worldwide. Two randomized trials have shown superiority of haplo-HSCT over UCBT [13,14], while most retrospective studies have shown similar outcomes compared with MUD and MSD transplants [15][16][17][18].…”