Myeloablative haploidentical BMT with posttransplant cyclophosphamide for hematologic malignancies in children and adults

Abstract

Promising results have been reported for patients with high-risk hematologic malignancies undergoing HLA-haploidentical bone marrow transplantation (haploBMT) with posttransplantation cyclophosphamide (PTCy), but there are few data on outcomes with myeloablative conditioning in this context. We report the results of a single-institution, prospective phase 2 trial of myeloablative haploBMT using busulfan-based or total body irradiation-based conditioning in 96 children or adults (median age, 42 years; range, 1-65 years) with high-risk hematologic malignancies. Recovery of neutrophils and platelets occurred at a median of 24 and 29 days. Engraftment of donor cells with chimerism >95% was achieved in 91%. The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and grades III to IV at day 100 was 11% and 4%, and of chronic GVHD at 6 and 12 months was 4% and 15%, with 6% moderate to severe. The cumulative incidence of nonrelapse mortality was 6% at 100 days and 11% at 1 year (19% in those aged >55 years). The cumulative incidence of relapse at 1 year was 35%; at 3 years, it was 43%. In multivariable analysis, relapse was associated with increased age (P = .02 for age 20-55 years and P = .02 for age >55 years) and with minimal residual disease before transplantation (P = .05). The overall survival at 1 and 3 years is 73% and 54%, and event-free survival at 1 and 3 years is 57% and 49%. We show that haploBMT with PTCy after myeloablative conditioning is safe and efficacious for adult and pediatric patients with hematologic malignancies. Careful consideration must be given to using myeloablative conditioning in patients age >55 years. This trial was registered at www.clinicaltrials.gov as #NCT00796562.

Conflict of interest statement

Conflict-of-interest-disclosure: None of the authors received any financial support for this trial. Currently, H.J.S. is on the speaker bureau for Jazz Pharmaceuticals. K.C. receives research support, is a consultant for, and is on the speaker bureau and advisory board for Jazz Pharmaceuticals. J.B.-M. is on a Drug Safety Monitoring Board for Incyte. I.G. receives research support from Merck Inc., Amgen, Amphivena, Celgene, and Genentech. L.L. receives research support from Genentech and Merck, serves on the speaker bureau for Merck, serves as a consultant and is on the advisory board for AbbVie, and is a patent holder for WindMIL Therapeutics. The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Treatment schemas. (A) Chemotherapy conditioning regimen. (B) TBI conditioning regimen. MMF, mycophenolate mofetil; po, by mouth; tid, thrice daily.

Figure 2.

Cumulative incidence of neutrophil and platelet engraftment. (A) Neutrophil engraftment. (B) Platelet engraftment.

Figure 3.

Acute and chronic GVHD. (A) Cumulative incidence of aGVHD grades II to IV and grades III to IV. (B) Overall and moderate to severe cGVHD.

Figure 4.

Cumulative incidence of NRM and relapse.

Figure 5.

OS and EFS.

Figure 6.

Pediatric/adolescent and young adult results. (A) Cumulative incidence of NRM and relapse. (B) Cumulative incidence of aGVHD grades II to IV and III to IV. (C) Cumulative incidence of overall and moderate to severe cGVHD. (D) OS and EFS.