Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study

SCETIDE, PIDTC, EBMT & ESID IEWP

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Background: CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium species infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT). Objective: We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics. Methods: We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables' relevance with respect to survival and cure. Results: Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 78.2%, 58.1%, and 72.3% 5 years after HSCT. Results were better in transplantations performed in 2000 or later and in children less than 10 years old at the time of HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT at 2 years or less from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC), and bone marrow–derived stem cells. Most rejections occurred after reduced-intensity or nonmyeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was 50% or greater donor in 85.2%. Conclusion: HSCT is curative in patients with CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS, and DFS. Prospective studies are required to compare the risks of HSCT with those of lifelong supportive therapy.

Original languageEnglish (US)
Pages (from-to)2238-2253
Number of pages16
JournalJournal of Allergy and Clinical Immunology
Volume143
Issue number6
DOIs
StatePublished - Jun 2019

Bibliographical note

Funding Information:
F.F. received an ESID Medium Term Fellowship. M. J. Cowan, C. C. Dvorak, and K. E. Sullivan are supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID), and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, Maryland (Public Health Service grant/cooperative agreements U54-AI082973 and R13-AI094943). The SCETIDE registry is funded by CEREDIH and the French Ministry of Health. Research was supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. F.F. received an ESID Medium Term Fellowship. M. J. Cowan, C. C. Dvorak, and K. E. Sullivan are supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID), and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, Maryland (Public Health Service grant/cooperative agreements U54-AI082973 and R13-AI094943). The SCETIDE registry is funded by CEREDIH and the French Ministry of Health. Research was supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. We thank data managers of the different centers for their support in data collection. We are grateful to all medical and nurse personnel of the participating clinical and transplant centers for patients' care. We are indebted to all the patients and their families for their participation in the study and trust. F.F. received an ESID Medium Term Fellowship. M. J. Cowan, C. C. Dvorak, and K. E. Sullivan are supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID), and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, Maryland (Public Health Service grant/cooperative agreements U54-AI082973 and R13-AI094943). The SCETIDE registry is funded by CEREDIH and the French Ministry of Health. Research was supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

Publisher Copyright:
© 2019 The Authors

Keywords

  • CD40 ligand
  • X-linked hyper-IgM syndrome
  • hematopoietic stem cell transplantation
  • primary immunodeficiency

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