Experience with a Reduced Toxicity Allogeneic Transplant Regimen for Non-CGD Primary Immune Deficiencies Requiring Myelo
- PDF / 606,951 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 11 Downloads / 149 Views
ORIGINAL ARTICLE
Experience with a Reduced Toxicity Allogeneic Transplant Regimen for Non-CGD Primary Immune Deficiencies Requiring Myeloablation Sharat Chandra 1,2 & Shanmuganathan Chandrakasan 3 & Blachy J. Dávila Saldaña 4 & Jack J. Bleesing 1,2 & Michael B. Jordan 1,2 & Ashish R. Kumar 1,2 & Michael S. Grimley 1,2 & Christa Krupski 1,2 & Stella M. Davies 1,2 & Pooja Khandelwal 1,2 & Rebecca A. Marsh 1,2 Received: 30 July 2020 / Accepted: 4 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Reduced toxicity regimen . allogeneic HCT . myeloablative HCT . primary immune deficiencies . Wiskott-Aldrich syndrome . CD40 ligand deficiency . primary HLH/XLP
Sharat Chandra, Shanmuganathan Chandrakasan,contributed equally as first author to this work. Pooja Khandelwal and Rebecca Marsh contributed equally as last author to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00888-2) contains supplementary material, which is available to authorized users. * Sharat Chandra [email protected] 1
Division of Bone Marrow Transplantation and Immune
Data Loading...
