Hematopoietic stem cell transplantation for CTLA-4 insufficiency across Europe: A European Society for Blood and Marrow Transplantation Inborn Errors Working Party study.

Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) insufficiency causes a primary immune regulatory disorder characterized by lymphoproliferation, dysgammaglobulinemia, and multiorgan autoimmunity including cytopenias and colitis.
Objective: We examined the outcome of hematopoietic stem cell transplantation (HSCT) for CTLA-4 insufficiency and study the impact of pre-HSCT CTLA-4 fusion protein (CTLA-4-Ig) therapy and pre-HSCT immune dysregulation on survival and immunologic outcome.
Methods: This was a retrospective study of HSCT for CTLA-4 insufficiency and 2q33.2-3 deletion from the European Society for Blood and Marrow Transplantation Inborn Errors Working Party. Primary end points were overall survival (OS) and disease- and chronic graft-versus-host disease-free survival (DFS). Secondary end point was immunologic outcome assessed by immune dysregulation disease activity (IDDA) score.
Results: Forty patients were included over a 25-year period. Before HSCT, 60% received CTLA-4-Ig, and median (range) IDDA score was 23.3 (3.9-84.0). Median (range) age at HSCT was 14.2 (1.3-56.0) years. Patients received peripheral blood stem cell (58%) or marrow (43%) from a matched unrelated donor (75%), mismatched unrelated donor (12.5%), or matched family donor (12.5%). Median (range) follow-up was 3 (0.6-15) years, and 3-year OS was 76.7% (58-87%) and DFS was 74.4% (54.9-86.0%). At latest follow-up, disease of 28 of 30 surviving patients was in disease-free remission with median IDDA reduction of 16. Probability of OS and DFS was greater in patients with lower disease activity before HSCT (IDDA < 23, P = .002 and P = .006, respectively). CTLA-4-Ig receipt did not influence OS or DFS. Cause of death was transplant related in 7 of 8 patients.
Conclusion: HSCT is an effective therapy to prevent ongoing disease progression and morbidity, with improving survival rates over time and in patients with lower pre-HSCT disease activity.
Competing Interests: Disclosure statement Supported by the National Institute for Health Research, University College London Hospitals Biomedical Research Centre (to E.C.M.). Data used in this study are not publicly available, but deidentified data may be available from the authors on reasonable request. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)