Reduced Intensity Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Pediatric Inherited Immune Defic
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ORIGINAL ARTICLE
Reduced Intensity Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Pediatric Inherited Immune Deficiencies and Bone Marrow Failure Syndromes Orly R. Klein 1 & Samantha Bapty 2 & Howard M. Lederman 3 & M. Elizabeth M. Younger 3 & Elias T. Zambidis 1 & Richard J. Jones 1 & Kenneth R. Cooke 1 & Heather J. Symons 1 Received: 5 June 2020 / Accepted: 22 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Allogeneic bone marrow transplantation (alloBMT) is the only cure for many primary immune deficiency disorders (PIDD), primary immune regulatory disorders (PIRD), and inherited bone marrow failure syndromes (IBMFS). Methods We report the results of 25 patients who underwent alloBMT using reduced intensity conditioning (RIC), alternative donors, and post-transplantation cyclophosphamide (PTCy). In an attempt to reduce regimen-related toxicities, we removed lowdose TBI from the prep and added mycophenolate mofetil and tacrolimus for graft-versus-host disease (GVHD) prophylaxis for all donor types in the latter 14 patients. Donors were haploidentical related (n = 14), matched unrelated (n = 9), or mismatched unrelated (n = 2). The median age was 9 years (range 5 months–21 years). Results With a median follow-up of 26 months (range 7 months–9 years), the 2-year overall survival is 92%. There were two deaths, one from infection, and one from complications after a second myeloablative BMT. Three patients developed secondary graft failure, one at 2 years and two at >3 years, successfully treated with CD34 cell boost in one or second BMT in two. The remaining 20 patients have full or stable mixed donor chimerism and are disease-free. The incidence of mixed chimerism is increased since removing TBI from the prep. The 6-month cumulative incidence of grade II acute GVHD is 17%, with no grade III–IV. The 1-year cumulative incidence of chronic GVHD is 14%, with severe of 5%. Conclusion This alloBMT platform using alternative donors, RIC, and PTCy is associated with excellent rates of engraftment and low rates of GVHD and non-relapse mortality, and offers a curative option for patients with PIDD, PIRD, and IBMFS. Trial registration ClinicalTrials.gov Identifier: NCT04232085 Keywords Blood and marrow transplantation . primary immune deficiency disorders . primary immune regulatory disorders . inherited bone marrow failure disorders . alternative donor . post-transplant cyclophosphamide
Introduction
* Heather J. Symons [email protected] 1
Hematologic Malignancies and Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
2
Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA
3
Division of Allergy and Immunology, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Allogeneic blood and marrow transplantation (alloBMT) is curative for many primary immune deficiency disorders (PIDD),
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