HLA-haploidentical stem cell transplantation for chronic granulomatous disease: an EBMT-IEWP retrospective study
Abstract
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.
Article Details
Authors (31)
Quentin Riller
8Université Paris Cité, Paris, France
Mathias Hauri
2Department of Stem Cell Transplantation, University Children's Hospital, Zürich, Switzerland
Su Han Lum
3Translational and Clinical Research Institute, Newcastle University, Great North Children’s Hospital, Newcastle upon Tyne, United Kingdom
Jeroen Knippenberg
3EBMT Office, Leiden, Netherlands
Tiarlan Sirait
4European Bone Marrow Transplantation, Leiden Study Unit, Leiden, The Netherlands
Alexandra Laberko
22Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Khalid Halahleh
10Department of Internal Medicine, Adult BMT Program, King Hussein Cancer Center, Amman, Jordan
Hasan Hashem
1King Hussein Cancer Center, Amman, Jordan
Musa Karakükcü
24Erciyes University, Faculty of Medicine, Kayseri, Turkey, Kayseri, Türkiye
Henrik Sengeloev
11Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Fulvio Porta
6Pediatric Oncohaematology and BMT Unit Children' s Hospital Spedali Civili, Brescia, Italy
Benedicte Bruno
33Unite d'Hematologie Pediatrique, Lille, France, Lille, France
Marco Zecca
Serap Aksoylar
9Ege University Pediatric BMT Centre, Izmir, Türkiye
Vincent Barlogis
18Department of Pediatric Hematology, La Timone Hospital, AP-HM, Marseille, France, Marseille, France
Catharina Schuetz
15Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Jochen Buechner
1Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway
Maura Faraci
13Institute G. Gaslini, Genova, Italy
Claudia Wehr
1University of Freiburg, Hematology, Oncology and Stem Cell Transplantation, Department of Medicine I, Faculty of Medicine, Freiburg, Germany
Wolfgang Holter
20Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
Karin Mellgren
21Pediatric Clinical Unit, Queen Silvia Children's Hospital, Gothenburg, Sweden
Franco Locatelli
IRCCS Ospedale Pediatrico Bambino Gesù Rome, Rome
Antonio Perez Martinez
Felipe Suarez
20Department of Hematology, Hôpital Necker, Paris, France
Despina Moshous
8Université Paris Cité, Pediatric Hematology-Immunology and Rheumatology Department, Necker-Enfants Malades Hospital, Paris, France, Paris, France
Andrew R. Gennery
Newcastle University
Dmitry Balashov
5Department of Pediatric Hematology, Oncology, and Immunology, Dmitry Rogachev National Medical Research Center, Moscow, Russia
Michael H. Albert
10Department of Pediatric Hematology and Oncology, Dr. von Hauner Children’s University Hospital, Ludwig Maximilian University, Munich, Germany
Mary Slatter
3Translational and Clinical Research Institute, Newcastle University, Great North Children’s Hospital, Newcastle upon Tyne, United Kingdom
Tayfun Güngör
12Department of Hematology/Oncology/Immunology, Gene Therapy, and Stem Cell Transplantation, Eleonore Foundation and Children’s Research Center, University Children’s Hospital, Zürich, Switzerland
Bénédicte Neven