Prospective PTCTC trial of myeloablative haplo-BMT with posttransplant cyclophosphamide for pediatric acute leukemias

Abstract

Promising results have been reported for adult patients with high-risk hematologic malignancies undergoing haploidentical bone marrow transplant (haploBMT) with post-transplantation cyclophosphamide (PTCy). We report results from the first multicenter trial for pediatric and young adult patients with high-risk acute leukemias and myelodysplastic syndrome (MDS) in the US and Canada in the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC). Nine centers transplanted 32 patients with acute leukemias or MDS with myeloablative conditioning (MAC), haploBMT with PTCy, mycophenolate mofetil, and tacrolimus. The median age was 12y (range 1-23y). Diagnoses included acute myeloid leukemia (n=15), acute lymphoid leukemia (n=11), mixed lineage leukemia (n=1), and MDS (n=5). Transplant-related mortality (TRM) at 180 days, our primary objective, was 0%. The cumulative incidence (CuI) of acute graft-versus-host disease (aGVHD) grade II at Day 100 was 13%. No patients developed aGVHD grades III-IV. The CuI of moderate-severe chronic GVHD (cGVHD) at 1 year was 4%. Donor engraftment occurred in 27/32 (84%). Primary graft failures included three patients that received suboptimal bone marrow grafts, all successfully engrafted after second transplants. The CuI of relapse at 1y was 32%, with more relapse in pre-BMT MRD+ versus MRD- patients. Overall survival at 1y and 2y is 77% and 73%, and event-free survival at 1y and 2y is 68% and 64%, respectively. We demonstrate no TRM or severe aGVHD, low cGVHD, and favorable relapse and survival rates. This successful pilot has led to a phase III trial comparing MAC haploBMT versus HLA-matched unrelated donors, now open in the Children's Oncology Group.

Haplo ever after: haplo PTCy for children

“…In this issue of Blood Advances , Fierro-Pineda et al 1 have successfully performed a prospective multicenter clinical trial through the Pediatric Transplantation and Cellular Therapy Consortium showing the safety and tolerability of myeloablative conditioning with posttransplant cyclophosphamide (PTCy) in pediatric patients receiving haploidentical bone marrow transplant (haploBMT) for hematologic malignancies. Although small single-center studies have been published using this platform, to our knowledge, this is the first prospective, multicenter trial of myeloablative haploBMT with PTCy in pediatric patients with hematologic malignancies, highlighting that the results are generalizable across multiple institutions.…”

“…The results of this trial 1 have set the stage for an open and enrolling Children’s Oncology Group randomized controlled trial of haploidentical transplantation (using PTCy or alpha-beta T-cell–depleted platforms) vs matched unrelated donor (MUD) hematopoietic stem cell transplantation in pediatric patients with high-risk hematologic malignancies. This prospective study will help answer the question of whether the outcomes of a haplo approach are similar or improved compared with a MUD for hematologic malignancies.…”