HLA-haploidentical stem cell transplantation for chronic granulomatous disease: an EBMT-IEWP retrospective study

Chronic granulomatous disease (CGD) is an inborn error of immunity characterized by defective NAD phosphate oxidase function, leading to impaired microbial killing, recurrent infections, and granulomatous inflammation. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for CGD, particularly effective when a fully HLA-matched donor is available. However, the place of HLA-haploidentical HSCT remains less established. This retrospective multicenter study analyzed outcomes of 64 patients with CGD (53 males; 46 with X-linked CGD) who underwent a first HSCT with HLA-haploidentical family donors, with either in vitro T-cell receptor (TCR)αβ/CD19 depletion or in vivo depletion using posttransplant cyclophosphamide (PTCY). The mean age at transplant was 5.8 years (range, 0-33). Patients exhibited a high disease burden before HSCT, with 45% experiencing infections in the 6 months before HSCT and 67% exhibiting inflammation. Outcomes in the entire cohort showed a 3-year overall survival, event-free survival (EFS), and grade 3 to 4 graft-versus-host disease (GVHD)-free EFS of 75.9%, 70.2%, and 56.1%, respectively, and were not affected by the type of depletion or age. The cumulative incidence (CI) of primary graft failure (PGF) was 20.6%. The CI of grade 2 to 4 acute GVHD was higher in the PTCY group (P = .04), whereas the CI of grade 3 to 4 GVHD was not. These results indicate that HLA-haploidentical HSCT is a feasible transplant option for patients with CGD lacking HLA-matched donors. Further refinement of transplant protocols is necessary to mitigate graft failure and acute GVHD, ultimately improving access and outcomes for this life-saving therapy.

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Journal
Blood
Published
2025-03-16
DOI
https://doi.org/10.1182/blood.2024026915
Citations
5
Primary Topic
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Type
article
Field-Weighted Citation Impact
3.99
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article

HLA-haploidentical stem cell transplantation for chronic granulomatous disease: an EBMT-IEWP retrospective study

Mathias Hauri‐Hohl, Alexandra Laberko, Bénédicte Neven, Quentin Riller et al.
5 citations
Blood
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
3.99
article

HLA-haploidentical stem cell transplantation for chronic granulomatous disease: an EBMT-IEWP retrospective study

Mathias Hauri‐Hohl, Alexandra Laberko, Bénédicte Neven, Quentin Riller, Andrew Richard Gennery, Su Han Lum, Franco Locatelli, Despina Moshous, Michael H. Albert, Karin Mellgren, Felipe Suárez, Henrik Sengeløv, Serap Aksoylar, Jochen Buechner, Hasan Hashem, Antonio Pérez‐Martínez, Vincent Barlogis, Marco Zecca, Maura Faraci, Wolfgang Holter, Tiarlan Sirait, Khalid Halahleh, Musa Karakükçü, Mary Anne Slatter, Claudia Wehr, Jeroen Knippenberg, Dmitry Balashov, Bénédicte Bruno, Tayfun Güngör, Catharina Schuetz, Fulvio Porta
article en
5 citations

Abstract

Chronic granulomatous disease (CGD) is an inborn error of immunity characterized by defective NAD phosphate oxidase function, leading to impaired microbial killing, recurrent infections, and granulomatous inflammation. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for CGD, particularly effective when a fully HLA-matched donor is available. However, the place of HLA-haploidentical HSCT remains less established. This retrospective multicenter study analyzed outcomes of 64 patients with CGD (53 males; 46 with X-linked CGD) who underwent a first HSCT with HLA-haploidentical family donors, with either in vitro T-cell receptor (TCR)αβ/CD19 depletion or in vivo depletion using posttransplant cyclophosphamide (PTCY). The mean age at transplant was 5.8 years (range, 0-33). Patients exhibited a high disease burden before HSCT, with 45% experiencing infections in the 6 months before HSCT and 67% exhibiting inflammation. Outcomes in the entire cohort showed a 3-year overall survival, event-free survival (EFS), and grade 3 to 4 graft-versus-host disease (GVHD)-free EFS of 75.9%, 70.2%, and 56.1%, respectively, and were not affected by the type of depletion or age. The cumulative incidence (CI) of primary graft failure (PGF) was 20.6%. The CI of grade 2 to 4 acute GVHD was higher in the PTCY group (P = .04), whereas the CI of grade 3 to 4 GVHD was not. These results indicate that HLA-haploidentical HSCT is a feasible transplant option for patients with CGD lacking HLA-matched donors. Further refinement of transplant protocols is necessary to mitigate graft failure and acute GVHD, ultimately improving access and outcomes for this life-saving therapy.

BloodVol. 145(21)
Oslo University Hospital (NO), Hôpital Necker-Enfants Malades (FR), Inserm (FR), University of Freiburg (DE), Université Paris Cité (FR), Aix-Marseille Université (FR), Université de Lille (FR), King Hussein Cancer Center (JO), Hospital Universitario La Paz (ES), Sahlgrenska University Hospital (SE), University Medical Center Freiburg (DE), Instituto de Salud Carlos III (ES), Istituto Giannina Gaslini (IT), Newcastle upon Tyne Hospitals NHS Foundation Trust (GB), Rigshospitalet (DK), German Center for Pediatric and Adolescent Rheumatology (DE), Ege University (TR), Assistance Publique Hôpitaux de Marseille (FR), Centre de Référence Déficits Immunitaires Héréditaires (FR), Lille’s Cardiology Hospital (FR), Assistance Publique – Hôpitaux de Paris (FR), European Society for Blood and Marrow Transplantation (NL), Drottning Silvias barn- och ungdomssjukhus (SE), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Hospital La Paz Institute for Health Research (ES), Centre for Biomedical Network Research on Rare Diseases (ES), Bambino Gesù Children's Hospital (IT), St Anna Children's Hospital (AT), Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (RU), University Children's Hospital Zurich (CH), Great North Children's Hospital (GB), Policlinico San Matteo Fondazione (IT), University of the Sacred Heart (JP), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University Hospital Carl Gustav Carus (DE), Technische Universität Dresden (DE), University of Brescia (IT), Ludwig-Maximilians-Universität München (DE), Newcastle University (GB), Erciyes University (TR), University of Gothenburg (SE)
Openalex Percentile: Top 6%
Neutrophil, Myeloperoxidase and Oxidative Mechanisms
3.99
DOISourceOpenAlex
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