Survival Outcomes After HLA-Haploidentical Relative Versus Matched Unrelated Donor Transplant in Acute Leukemias and MDS

In patients with acute leukemias or myelodysplastic syndromes (MDS), those who underwent haploidentical relative hematopoietic cell transplantation (haploHCT) had higher rates of grade 3-4 graft-versus-host disease (GVHD) and mortality compared with those who underwent HCT with a matched unrelated donor (MUD), according to results published in Blood.

“Access to transplantation extends survival and patients who are likely to benefit from HCT should be offered haploHCT if a MUD is not readily available,” said study author Mahasweta Gooptu, MD, of Dana-Farber Cancer Institute.

For this study, Dr. Gooptu obtained data from the Center for International Blood and Marrow Transplant Research (CIBMTR). A total of 2,320 patients in the dataset underwent transplantation across 111 centers in the U.S. between 2011 and 2018. Both MUD HCT and haploHCT were performed by 53 centers, while 56 centers used only haploHCT and two centers used only MUD HCT.

Patients had diagnoses of acute myeloid or lymphoblastic leukemia in first or second complete remission, or MDS. The patients received myeloablative or reduced-intensity conditioning regimens, post-transplant cyclophosphamide (PTCy), as well as a calcineurin inhibitor (CNI) with mycophenolate mofetil for GVHD prophylaxis. The use of PTCy-containing GVHD prophylaxis for myeloablative MUD HCTs represents a recent approach to manage severe GVHD, the investigators noted.

The median follow-up periods after haploHCT and MUD HCT among patients who received reduced-intensity regimens were 29 months and 25 months, respectively.

In this analysis, graft failure was defined as the failure to achieve an absolute neutrophil count (ANC) ≥0.5×109/L, decline in ANC to <0.5×109/L without recovery following achievement of an ANC ≥0.5×109/L, myeloid donor chimerism (<5%), or second transplant.

The two-year graft failure rate in patients who received reduced-intensity regimens was lower after MUD compared with haploHCT (3% vs. 11%, respectively; p<0.001). In addition, the use of MUD HCT was associated with lower rates of acute grade 2-4 GVHD (hazard ratio [HR] = 0.70; p=0.022), acute grade 3-4 GVHD (HR=0.41; p=0.016), and non-relapse mortality (HR=0.33; p<0.0001) compared with haploHCT.

In contrast, MUD transplantation was associated with significantly higher disease-free survival (55% vs. 41%; HR=0.74; p=0.008) as well as overall survival (OS; 67% vs. 54%; HR=0.65; p=0.001), the latter of which served as the study’s primary endpoint (TABLE).

Among the patients who received myeloablative regimens, the use of MUD (median follow-up = 25 months) versus haploHCT (median follow-up = 12 months) was associated with significantly higher platelet recovery by day 100 (93% vs. 87%, respectively; p<0.0001) and lower grade 3-4 acute GVHD (HR=0.37; p=0.05) and chronic GVHD (HR=0.66; p=0.05).

A subset analysis that included white patients and recipients of peripheral blood graft between 2016 and 2018 found MUD HCT was associated with a lower risk of non-relapse mortality (HR=0.34; 95% CI 0.15-0.73; p=0.006) and higher disease-free survival (HR=0.69; 95% CI 0.50-0.94; p=0.018) and OS (HR=0.57; 95% CI 0.39-0.84; p=0.004) after reduced-intensity conditioning.

Overall, the data from this analysis favor MUD HCT, the authors concluded. “Lower survival after reduced-intensity haploHCT and a higher incidence of severe acute GVHD after myeloablative HCT confirm donor-recipient human leukocyte antigen (HLA) matching is an important determinant of outcomes after transplantation,” they wrote. However, this study is limited by its reliance on data reported in a large transplant registry. The researchers added that the modest follow-up of their cohorts limited their ability to investigate the effect that severe acute and chronic GVHD has on long-term survival in this patient population.

The authors report no relevant conflicts of interest.


Gooptu M, Romee R, St Martin A, et al. HLA Haploidentical versus matched unrelated donor transplants with post-transplant cyclophosphamide based prophylaxis. [published online ahead of print, 2021 Apr 13]. Blood. doi: 10.1182/blood.2021011281.