Impact of Abatacept-based Graft-versus-host Disease Prophylaxis on Transplant Outcomes in Children With Hemoglobinopathies: a Systematic Review
Year: 2026
Type: article
Study design: Systematic Review
Abstract: Introduction Sickle cell disease and transfusion-dependent β-thalassemia are major grounds for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. While this procedure has curative potential, graft-versus-host disease (GVHD) limits its success. Abatacept (through its inhibitory action on T-cell costimulation via the CD80/CD86–CD28 axis), may improve GVHD incidence, overall survival, graft rejection, and immune-mediated toxicity. Objective This systematic review aimed to critically appraise the impact of abatacept-containing prophylactic regimens on transplant outcomes in pediatric patients with hemoglobinopathies undergoing allo-HSCT. Methods This systematic review was conducted in accordance with PRISMA guidelines, using PubMed as the sole database. The search strategy combined MeSH terms and free-text terms across four conceptual blocks: abatacept (and its synonyms, including CTLA4-Ig), graft-versus-host disease prophylaxis, hematopoietic stem cell transplantation, hemoglobinopathies (encompassing sickle cell disease and beta-thalassemia), and pediatric population, connected by Boolean operators (AND/OR), with an additional NOT operator applied to exclude animal studies lacking a human component. Studies published between 2020 and 2026 were considered eligible. Publications within the date range, human subject studies, and pediatric populations were included. Exclusion criteria included adult-only studies or studies with unextractable or qualitative pediatric subgroup outcome data. Separately and blindly, studies were chosen. The selection process, included studies, and main findings were characterized by a qualitative synthesis. Results The literature search identified seven studies, six of which met the eligibility criteria and were included in the qualitative synthesis. Collectively, 222 patients were analyzed, of whom 160 received abatacept-containing GVHD prophylaxis; 134 of these had a confirmed diagnosis of hemoglobinopathy. The included studies evaluated abatacept-based GVHD prophylaxis in children undergoing allo-HSCT from matched related, matched unrelated, and haploidentical donors. The addition of abatacept was consistently associated with a reduction in severe (grade III–IV) acute GVHD. Its effect on chronic GVHD was more heterogeneous: extended-duration regimens showed significant reductions, whereas shorter regimens were associated with persistently high incidence (up to 57%). Overall survival remained high (87-100%) among intervention groups, exceeding that of control groups in three comparative studies. Reductions in endothelial injury syndromes and transplant-related mortality were also observed. Viral reactivation (cytomegalovirus, Epstein-Barr virus) occurred in both groups without a consistent statistically significant difference between them, representing the principal safety concern identified. Conclusion Adding abatacept to GVHD prophylaxis may improve GVHD incidence, overall survival, graft rejection, and immune-mediated toxicity. Abatacept reduced severe acute GVHD safely and effectively, with more consistent benefit against chronic GVHD with prolonged-duration regimens. However, observational studies and single-arm cohorts with heterogeneous protocols and small sample sizes provide most of the evidence. Insufficient data on quality of life, fertility, and long-term outcomes necessitates adequately powered randomized controlled trials.
Institution: Faculdade de Ciências Médicas de Minas Gerais
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223137359