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The following is a summary of “Hematopoietic stem cell transplantation for CTLA-4 insufficiency across Europe: A European Society for Blood and Marrow Transplantation Inborn Errors Working Party study,” published in the August 2024 issue of Allergy and Immunology by Tsilifis et al.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) insufficiency is a primary immune regulatory disorder characterized by lymphoproliferation, dysgammaglobulinemia, multiorgan autoimmunity, and cytopenias and colitis. This study aimed to evaluate the outcomes of hematopoietic stem cell transplantation (HSCT) in patients with CTLA-4 insufficiency and assess the impact of pre-HSCT CTLA-4 fusion protein (CTLA-4–Ig) therapy and immune dysregulation on survival and immunologic outcomes. In a retrospective analysis, data were gathered from the European Society for Blood and Marrow Transplantation Inborn Errors Working Party, covering 25 years. 

The primary endpoints were overall survival (OS) and disease- and chronic graft-versus-host disease-free survival (DFS), with immune dysregulation disease activity (IDDA) scores used as a secondary measure of immunologic outcome. The cohort included 40 patients with a median age of 14.2 years (range: 1.3-56.0) at HSCT. Of these, 60% received pre-HSCT CTLA-4–Ig therapy, and the median IDDA score was 23.3 (range: 3.9-84.0). Patients underwent transplantation using peripheral blood stem cells (58%) or marrow (43%), sourced from matched unrelated donors (75%), mismatched unrelated donors (12.5%), or matched family donors (12.5%). The median follow-up period was 3 years (range: 0.6-15 years). Three-year OS was 76.7% (CI: 58-87%), while DFS was 74.4% (54.9-86.0%). Among the 30 surviving patients, 28 achieved disease-free remission, with a median IDDA reduction of 16 points. 

Notably, lower pre-HSCT disease activity (IDDA < 23) was associated with significantly better OS (P = .002) and DFS (P = .006). However, pre-HSCT treatment with CTLA-4–Ig did not significantly affect OS or DFS. Seven of the eight deaths were attributed to transplant-related complications. In conclusion, HSCT emerges as a viable treatment option for halting disease progression and reducing morbidity in CTLA-4 insufficiency, with outcomes improving over time, particularly in patients presenting with lower disease activity before transplantation. These findings underscore the importance of early intervention and careful management of immune dysregulation before HSCT.

Source: sciencedirect.com/science/article/pii/S0091674924009035