Experience with a Reduced Toxicity Allogeneic Transplant Regimen for Non-CGD Primary Immune Deficiencies Requiring Myeloablation

• Type of Material: Article
• Authors: Sharat Chandra, Cincinnati Children’s Hospital Medical Center; Shanmuganathan Chandrakasan, Emory University; Blachy J Dávila Saldaña, Children’s National Hospital, Washington; Jack J Bleesing, Cincinnati Children’s Hospital Medical Center; Michael B Jordan, Cincinnati Children’s Hospital Medical Center; Ashish R Kumar, Cincinnati Children’s Hospital Medical Center; Michael S Grimley, Cincinnati Children’s Hospital Medical Center; Christa Krupski, Cincinnati Children’s Hospital Medical Center; Stella M Davies, Cincinnati Children’s Hospital Medical Center; Pooja Khandelwal, Cincinnati Children’s Hospital Medical Center; Rebecca A Marsh, Cincinnati Children’s Hospital Medical Center
• Language: English
• Date: 2020-10-16
• Publisher: SPRINGER/PLENUM PUBLISHERS
• Publication Version: Final Published Version
• Copyright Statement: © 2020, Springer Science Business Media, LLC, part of Springer Nature
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s10875-020-00888-2
• Title of Journal or Parent Work: JOURNAL OF CLINICAL IMMUNOLOGY
• Volume: 41
• Issue: 1
• Start Page: 89
• End Page: 98
• Keywords: Reduced toxicity regimen; primary HLH; primary immune deficiencies; CHIMERISM; ALEMTUZUMAB; HEMATOPOIETIC-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; myeloablative HCT; Immunology; CD40 ligand deficiency; Life Sciences & Biomedicine; BONE-MARROW-TRANSPLANTATION; FLUDARABINE; allogeneic HCT; XLP; IMMUNODEFICIENCY; SURVIVAL; Wiskott-Aldrich syndrome; Science & Technology; CHILDREN

Abstract

Purpose: A need exists for reduced toxicity conditioning regimens that offer less toxicity while maintaining myeloablation, especially for primary immune deficiencies where myeloablation or high donor myeloid chimerism is required to achieve cure. We adapted a busulfan and fludarabine regimen by Gungor et al. for children and young adults undergoing allogeneic HCT for non-CGD primary immune deficiencies requiring myeloablation or high donor myeloid chimerism, and herein report our experience. Methods: We retrospectively reviewed records of 41 consecutive patients who underwent allogeneic HCT for Wiskott-Aldrich syndrome (n = 12), primary HLH/XLP (n = 10), CD40L deficiency (n = 7), or other (n = 12) primary immune deficiencies with a conditioning regimen containing pharmacokinetic-guided busulfan dosing which achieved a cumulative AUC between 57 and 74 mg/L × h (65–80% of conventional myeloablative exposure), along with fludarabine and alemtuzumab or anti-thymocyte globulin at 3 transplant centers between 2014 and 2019. Results: Forty-one patients underwent a first (n = 33) or second (n = 8) allogeneic HCT. Median age was 2.3 years (range, 0.3 years–19.8 years). All but one patient (97.5%) achieved neutrophil recovery at a median of 14 days (range, 11–34 days). One patient developed sinusoidal obstruction syndrome and two patients developed diffuse alveolar hemorrhage. Four patients developed grades II–IV acute GVHD. Three patients developed chronic GVHD. One-year overall survival was 90% (95% confidence interval [CI] 81–99%) and event-free survival was 83% (95% CI 71–94%). Conclusions: Our experience suggests that a reduced toxicity busulfan-fludarabine regimen offers low toxicity, low incidence of grades 2–4 GVHD, durable myeloid engraftment, and excellent survival, and may be considered for a variety of primary immune deficiencies where myeloablative HCT is desired.