Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning

Abstract

Haplo-identical transplant with posttransplant cyclophosphamide (haplo) and umbilical cord blood transplant supported by third-party CD34 cells (haplo-cord) are competing approaches to alternative donor transplant. We compared, in adults younger than age 60 years, the outcomes of 170 haplo at 1 institution with that of 137 haplo-cord at 2 other institutions. All received reduced intensity conditioning with fludarabine and melphalan ± total body irradiation. GVHD prophylaxis for haplo consisted of cyclophosphamide, tacrolimus, and mycophenolate, whereas haplo-cord received antithymocyte globulin, tacrolimus, and mycophenolate. Haplo transplant used mostly bone marrow, and peripheral blood stem cells were used in haplo-cord transplants. Haplo-cord were older and had more advanced disease. Haplo-cord hastened median time to neutrophil (11 vs 18 days, P = .001) and platelet recovery (22 vs 25 days, P = .03). At 4 years, overall survival (OS) was 50% for haplo-cord vs 49% for haplo. Progression-free survival (PFS) was 40% for haplo-cord vs 45% for haplo. In multivariate analysis, the disease risk index was significant for OS (hazard ratio, 1.8; 95% confidence interval, 1.48-2.17; P = .00) and PFS. Total body irradiation was associated with decreased recurrence and improved PFS, age >40 with increased nonrelapse mortality. The type of transplant had no effect on OS, PFS, relapse, or nonrelapse mortality. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) by day 100 was 16% after haplo-cord vs 33% after haplo (P < .0001), but grade 3-4 GVHD was similar. Chronic GVHD at 1 year was 4% after haplo-cord vs 16% after haplo (P < .0001). Haplo or haplo-cord results in similar and encouraging outcomes. Haplo-cord is associated with more rapid neutrophil and platelet recovery and lower acute and chronic GVHD. Institutional review board authorization for this retrospective study was obtained at each institution. Some patients participated in trials registered at www.clinicaltrials.gov as #NCT01810588 and NCT 01050946.

Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

“…Multiple strategies are under investigation to improve the safety and efficacy of CBT. Ex vivo expansion of cord blood units [47][48][49] and co-infusion of haploidentical PBSC grafts with cord blood units [50] may allow faster engraftment and reduce the risk of graft failure with CBT. The single-center retrospective analysis by Milano et al showed that CBT may offer a better graft-versusleukemia (GVL) effect and lower the risk of relapse in patients with measurable residual disease (MRD) before transplantation compared to unrelated donor transplantation [51].…”

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“…Our result was consistent with Margaret's one that the incidence of grade II-IV acute GVHD in dUCBT recipients was higher than that in single UCBT recipients, but not grade III-IV aGVHD (31). Besien et al showed that cumulative incidence of grade II-IV acute GVHD was 16% after haplo-cord HSCT and 33% after haplo-HSCT (p <0.0001), but grade III-IV GVHD was similar (25). Kwon et al had similar results on treating AML.…”

“…The haploidentical graft serves as an early myeloid bridge for the recipient to support the immune system, which provides the rapid initial granulocyte and platelet recovery. This role of "myeloid bridge" was observed and confirmed for cord engraftment in patients receiving haplo-cord HSCT (25,26). There was a similar result in our study; myeloid engraftment occurred at a median of 14 days for patients with haplo-cord HSCT that was earlier than the median of 17 days in single cord HSCT recipients.…”

“…For platelet engraftment, the median time to engraftment of 17 days significantly sooner in haplo-cord group compared with the single cord group. The results might be superior to other studies of cord blood transplant supported by third-party CD34 + cells, in which the median time to platelet recovery was 25-35 days (25,27).…”

Hematopoietic Cell Transplantation in the Treatment of Newly Diagnosed Adult Acute Myeloid Leukemia: An Evidence-Based Review from the American Society of Transplantation and Cellular Therapy

“…The major limitation of using CBU is a relatively lower hematopoietic stem cell dose per unit for an adult recipient, leading to delayed engraftment and increased infectious complications and resultant NRM. Several strategies are under investigation to overcome this limitation to shorten the duration of neutropenia such as double-cord transplant [78], ex vivo expanded CBU [79], and coinfusion of a haploidentical RD graft with CBU (haplo-cord transplant) [80].…”