Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors

Abstract

We evaluated 917 adult lymphoma patients who received haploidentical (n = 185) or HLA-matched unrelated donor (URD) transplantation either with (n = 241) or without antithymocyte globulin (ATG; n = 491) following reduced-intensity conditioning regimens. Haploidentical recipients received posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, whereas URD recipients received calcineurin inhibitor-based prophylaxis. Median follow-up of survivors was 3 years. The 100-day cumulative incidence of grade III-IV acute GVHD on univariate analysis was 8%, 12%, and 17% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .44). Corresponding 1-year rates of chronic GVHD on univariate analysis were 13%, 51%, and 33%, respectively (P < .001). On multivariate analysis, grade III-IV acute GVHD was higher in URD without ATG (P = .001), as well as URD with ATG (P = .01), relative to haploidentical transplants. Similarly, relative to haploidentical transplants, risk of chronic GVHD was higher in URD without ATG and URD with ATG (P < .0001). Cumulative incidence of relapse/progression at 3 years was 36%, 28%, and 36% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .07). Corresponding 3-year overall survival (OS) was 60%, 62%, and 50% in the 3 groups, respectively, with multivariate analysis showing no survival difference between URD without ATG (P = .21) or URD with ATG (P = .16), relative to haploidentical transplants. Multivariate analysis showed no difference between the 3 groups in terms of nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). These data suggest that reduced-intensity conditioning haploidentical transplantation with posttransplant cyclophosphamide does not compromise early survival outcomes compared with matched URD transplantation, and is associated with significantly reduced risk of chronic GVHD.

Figure 1

Cumulative incidence of GVHD. (A) Acute GVHD II-IV. Cumulative incidence of grade II-IV acute GVHD in recipients of haploidentical donor, unrelated donor with ATG, and unrelated donor without ATG allo-HCT (overall, P = .07). (B) Chronic GVHD. Cumulative incidence of chronic GVHD in recipients of haploidentical donor, unrelated donor with ATG, and unrelated donor without ATG allo-HCT (overall, P < .001 at 1 year and 2 years).

Figure 2

Cumulative incidence and Kaplan-Meier estimates. (A) NRM. Cumulative incidence of NRM in recipients of haploidentical donor, unrelated donor with ATG, and unrelated donor without ATG allo-HCT (overall, P = .08 at 3 years). (B) Relapse/progression. Cumulative incidence of lymphoma relapse/progression in recipients of haploidentical donor, unrelated donor with ATG, and unrelated donor without ATG allo-HCT (overall, P = .07 at 3 years). (C) PFS. Kaplan-Meir estimate of PFS in recipients of haploidentical donor, unrelated donor with ATG, and unrelated donor without ATG allo-HCT (overall, P = .02 at 3 years). (D) OS. Kaplan-Meier estimate of OS in recipients of haploidentical donor, unrelated donor with ATG, and unrelated donor without ATG allo-HCT (overall, P = .02 at 3 years).