Reduced Intensity Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Pediatric Inherited Immune Deficiencies and Bone Marrow Failure Syndromes.

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 low-dose 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.

• Authors: Orly R Klein, Samantha Bapty, Howard M Lederman, M Elizabeth M Younger, Elias T Zambidis, Richard J Jones, Kenneth R Cooke, Heather J Symons
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 41 Issue 2 Pg. 414-426 (02 2021) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 33159275 (Publication Type: Journal Article)

Chemical References

• Cyclophosphamide
• Mycophenolic Acid
• Tacrolimus

Topics

• Adolescent
• Adult
• Bone Marrow Failure Disorders (drug therapy)
• Bone Marrow Transplantation (adverse effects)
• Child
• Child, Preschool
• Cyclophosphamide (therapeutic use)
• Disease-Free Survival
• Female
• Graft vs Host Disease (drug therapy)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Immunologic Deficiency Syndromes (drug therapy)
• Infant
• Infant, Newborn
• Male
• Mycophenolic Acid (pharmacology)
• Tacrolimus (therapeutic use)
• Tissue Donors
• Transplantation Conditioning (methods)
• Young Adult