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Hematopoietic Cell Transplantation for Adenosine Deaminase Severe Combined Immunodeficiency—Improved Outcomes in the Modern Era

Lookup NU author(s): Dr Aisling Flinn, Dr Su Han Lum, Dr Zohreh Nademi, Dr Stephen Owens, Dr Eleri Williams, Dr Terence Flood, Professor Sophie HambletonORCiD, Professor Mary Slatter, Professor Andrew GenneryORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2022, The Author(s). Current treatment for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) includes enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplant (HSCT), or ex vivo corrected autologous hematopoietic stem cell gene therapy. Historic data show HSCT survival is superior using unconditioned matched sibling and family compared to matched unrelated and haploidentical donors. Recent improvement in HSCT outcomes prompted us to retrospectively examine HSCT survival and long-term graft function in ADA-SCID transplanted at our center. Thirty-three ADA-deficient patients received HSCT between 1989 and 2020, with follow-up data to January 2021. Chemotherapy conditioning regimens were defined as myeloablative (MAC—busulfan/cyclophosphamide), reduced-toxicity myeloablative (RT-MAC—treosulfan-based, since 2007), or no conditioning. Serotherapy used included alemtuzumab (with or without other conditioning agents) or antithymocyte globulin (ATG). ERT was introduced routinely in 2010 until commencement of conditioning. Median age at HSCT was 3.2 (0.8–99.8) months. Twenty-one (63.6%) received stem cells from unrelated or haploidentical donors. Seventeen (51.5%) received chemotherapy conditioning and 16 (48.5%) received alemtuzumab. Median follow-up was 7.5 (0.8–25.0) years. Overall survival (OS) and event-free survival (EFS) at 8 years were 90.9% (95% CI: 79.7–100.0%) and 79% (55–91%), respectively. OS after 2007 (n = 21) was 100% vs 75% before 2007 (n = 12) (p = 0.02). Three (9.1%) died after HSCT: two from multiorgan failure and one from unexplained encephalopathy. There were no deaths after 2007, among those who received ERT and treosulfan-based conditioning pre-HSCT. Ten (30.3%) developed acute GvDH (3 grade II, 2 grade III); no chronic GvHD was observed. In the modern era, conditioned HSCT with MUD has a favorable outcome for ADA-deficient patients.

Publication metadata

Author(s): Ghimenton E, Flinn A, Lum SH, Leahy TR, Nademi Z, Owens S, Williams E, Flood T, Hambleton S, Slatter M, Gennery AR

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Immunology

Year: 2022

Pages: Epub ahead of print

Online publication date: 15/03/2022

Acceptance date: 21/02/2022

Date deposited: 28/03/2022

ISSN (print): 0271-9142

ISSN (electronic): 1573-2592

Publisher: Springer Nature


DOI: 10.1007/s10875-022-01238-0


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