Hematopoietic Stem Cell Transplantation in ADA-SCID: A Multicenter and Multinational Latin American Report

Introduction Adenosine deaminase (ADA) deficiency accounts for 10-15% of severe combined immunodeficiency cases. Treatment options include enzyme replacement therapy (ERT), gene therapy, and hematopoietic stem cell transplantation (HSCT). We report a multicenter case series of Latin American patients with ADA-SCID treated with HSCT. Methods Participants of the monthly online Latin American Society for Immunodeficiencies HSCT meetings reported data from eleven patients who underwent HSCT between 2013 and 2023. Results Six patients were female. Median age at diagnosis was 5.1 months (range: 0.9–50.0). Presentations included severe bacterial infections (5/11), viral pneumonia (5/11), diarrhea (2/11), pneumocystis pneumonia (2/11), oral candidiasis (2/11), and family history (1/11). Diagnosis was confirmed by genetic testing (7/11), enzyme assay (2/11), or immunophenotype and clinical features (2/11). Ten patients received Bacillus Calmette–Guérin vaccination; seven developed complications (three local, four disseminated). ERT was used in three cases. Median age at HSCT was 9.7 months (range: 3.7–54.4). Donors included matched family (3), unrelated adults (5), unrelated cord blood (2), and one haploidentical donor. Conditioning regimens varied; three patients received no conditioning. Graft versus host disease (GVHD) prophylaxis included a calcineurine inhibitor (10/11), antithymocyte globulin (7/11), antimetabolites (5/11), and posttransplant cyclophosphamide (2/9). Three patients died after transplant due to multiorgan failure, acute respiratory distress syndrome, and pneumonia. Median follow-up is 3.6 years (range: 0.1–10.7); overall survival is 72.7%. Acute GVHD occurred in 7/10 evaluable patients (3 with grade III–IV). Complications among 8 long-term survivors included EBV reactivation (6/8), invasive aspergillosis (2/8), neurological disabilities (7/8), hypothyroidism (2/8), and dermatofibrosarcoma protuberans (1/8). All patients engrafted; three have mixed chimerism. All are off intravenous immunoglobulins and 6/7 have normal lymphocyte subsets. Conclusion HSCT for ADA-SCID is feasible in resource-limited settings. This report shows encouraging outcomes despite significant clinical challenges.