Haploidentical Versus Matched Unrelated Donor Transplants Using Post-Transplantation Cyclophosphamide for Lymphomas

Abstract

When using post-transplantation cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis for lymphoma patients, it is currently unknown whether a matched unrelated donor (MUD) or a haploidentical related donor is preferable if both are available. In this study we wanted to test whether using a haploidentical donor has the same results of a MUD. A total of 2140 adults (34% Center for International Blood and Marrow Transplant Research, 66% European Society for Blood and Marrow Transplantation registry) aged ≥18 years who received their first haploidentical hematopoietic cell transplantation (haplo-HCT) or MUD-HCT (8/8 match at HLA-loci A, B, C, and DRB1) for lymphoma using PTCy-based GVHD prophylaxis from 2010 to 2019 were retrospectively analyzed. The majority of both MUD and haploidentical HCTs received reduced intensity/nonmyeloablative conditioning (74% and 77%, respectively) and used a peripheral blood stem cell graft (91% and 60%, respectively) and a 3-drug GVHD prophylaxis (PTCy + calcineurin inhibitor + MMF in 54% and 90%, respectively). Haploidentical HCT has less favorable results versus MUD cohort in terms of overall mortality (hazard ratio [HR= = 1.69; 95% confidence interval [CI], 1.30-2.27; P < .001), progression-free survival (HR=1.39; 95% CI, 1.10-1.79; P = .008), nonrelapse mortality (HR = 1.93; 95% CI, 1.21-3.07; P = .006), platelet engraftment (HR = 0.69; 95% CI, 0.59-0.80; P < .001), acute grade 2-4 GVHD incidence (HR = 1.65; 95% CI, 1.28-2.14; P < .001), and chronic GVHD (HR = 1.79; 95% CI, 1.30-2.48, P < .001). No significant differences were observed in terms of relapse and neutrophil engraftment. Adjusting for propensity score yielded similar results. Whenever MUD is available in a timely manner, it should be preferred over a haploidentical donor when using PTCy-based GVHD prophylaxis for patients with lymphoma.

Keywords: Haploidentical donor; Lymphoma; Matched unrelated donor; Post-transplant cyclophosphamide.

Figure 1:

Kaplan-Meier estimates and cumulative incidence. (A) Overall survival: 2-year OS was 63% (95% CI 61–66%) and 73% (95%CI 67–79%) in the haploidentical and matched unrelated groups, P=0.007. (B) Progression free survival: 2-year PFS was 53% (95% CI 50–55%) and 63% (95%CI 57–69%) in the haploidentical and matched unrelated groups, P=0.004. (C) Non-relapse mortality: 2-year NRM was 21% (95% CI 19–23%) and 15% (95%CI 10–19%) in the haploidentical and matched unrelated groups, P=0.024. (D) Relapse: 2-year risk of lymphoma relapse was 27% (95% CI 25–29%) and 22% (95%CI 17–27%) in the haploidentical and matched unrelated groups, P=0.21.

Figure 2:

Forest plot showing the results of multivariate analysis of patients with lymphomas undergoing haploidentical donor versus matched unrelated donor allogeneic transplantation using post-transplant cyclophosphamide based graft-versus-host disease prophylaxis. HR to the right of 1.0 favor MUD for all outcomes except ANC and platelets. For ANC and platelets, HR to the left of 1.0 favor MUD.