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

CD40 Ligand / deficiency Child Child, Preschool Hematopoietic Stem Cell Transplantation Humans Infant Infant, Newborn Treatment Outcome X-Linked Combined Immunodeficiency Diseases / mortality

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

Journal

The Journal of allergy and clinical immunology

ISSN: 1097-6825

Titre abrégé: J Allergy Clin Immunol

Pays: United States

ID NLM: 1275002

Informations de publication

Date de publication:
06 2019

Historique:

received: 28 03 2018

revised: 20 12 2018

accepted: 31 12 2018

pubmed: 21 1 2019

medline: 9 6 2020

entrez: 21 1 2019

Statut: ppublish

Résumé

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). We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics. 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. 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%. 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.

Sections du résumé

BACKGROUND

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.

Identifiants

DOI: 10.1016/j.jaci.2018.12.1010 PMID: 30660643

pubmed: 30660643

pii: S0091-6749(19)30034-X

doi: 10.1016/j.jaci.2018.12.1010

pii:

doi:

Substances chimiques

CD40 Ligand 147205-72-9

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

2238-2253

Subventions

Organisme : NIAID NIH HHS

ID : U54 AI082973

Pays : United States