2025-12-22 | 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.
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2025-11-25 | Outcomes following matched sibling donor transplantation for severe combined immunodeficiency: a report from the PIDTC
ABSTRACT: The Primary Immune Deficiency Treatment Consortium performed a retrospective analysis of 133 patients with severe combined immunodeficiency (SCID) receiving matched sibling donor (MSD) hematopoietic cell transplantation (HCT) between 1980 and 2023 at 30 North American institutions. In this largest cohort of MSD outcomes in patients with SCID to date, we examined the impact of conditioning regimen and graft-versus-host disease (GVHD) prophylaxis on survival and immune recovery. Outcomes after MSD HCT for SCID were excellent. Patients without an active infection or failure to thrive (FTT) at the time of HCT had 5-year overall survival superior to those with infection or FTT. Acute and chronic GVHD outcomes were independent of GVHD prophylaxis, conditioning regimen, SCID type, or presence of maternal engraftment. Patients without active infection at the time of HCT had superior chronic GVHD-free event-free survival vs those with infection. T-cell reconstitution at 6 months was less likely achieved with use of GVHD prophylaxis or serotherapy, and in patients with leaky SCID or Omenn syndrome. At 6 months, 1 year, and 2-5 years, T-cell reconstitution was less likely with ADA, DCLRE1C, or RAG genotype. B-cell reconstitution at 1 year and 2-5 years was negatively affected by development of grade 2 to 4 or 3 to 4 acute GVHD. Conditioning did not affect T- or B-cell reconstitution. Our data suggest omitting conditioning and GVHD prophylaxis for patients with typical SCID did not negatively affect 5-year outcomes after MSD HCT, but the data are insufficient to recommend this approach for best long-term outcomes. This trial was registered at www.clinicaltrials.gov as #NCT01186913 and #NCT01346150.
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2025-11-21 | Dupilumab for atopic manifestations in pediatric patients with inborn errors of immunity: efficacy and safety in a genetically diverse cohort
Background Inborn Errors of Immunity (IEI) are monogenic disorders that predispose patients to infections, autoimmunity, atopy, and malignancies. Severe Th2-driven atopic dermatitis and asthma are common in several IEIs, including DOCK8 deficiency, STAT3 loss-of-function, and Wiskott–Aldrich syndrome, often refractory to conventional therapies. Dupilumab, a monoclonal antibody targeting IL-4Rα, has shown promise in managing recalcitrant atopic dermatitis and asthma, but data in immunocompromised pediatric populations remain limited. Methods We conducted a single-center, retrospective observational cohort study with prospective follow-up of ten pediatric patients with genetically confirmed IEI and atopic manifestations. Patients received subcutaneous dupilumab (300 mg every 4 weeks for atopic dermatitis; every 2 weeks for severe asthma). Outcomes were assessed using the Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), Childhood Asthma Control Test (C-ACT), eosinophil counts, and infection frequency across four time points (baseline, 6 months, 12 months, >18 months). Results The cohort included ten patients (6 males, 4 females) with mutations in DOCK8 (n=5), CARD11 (n=2), STAT3 LOF (n=1), ADA (n=1), and PEPD (n=1). Of ten patients, nine received dupilumab for atopic dermatitis. Baseline EASI and DLQI scores were 34.33 and 25.0, respectively. Following dupilumab therapy, mean EASI decreased to 2.67 (p<0.001) and DLQI improved to 2.67 (p<0.001), with sustained response observed over 18 months. Peripheral eosinophil counts declined from 2.0×10 9 /L to 0.45×10 9 /L (p<0.001). One patient with severe asthma achieved C-ACT improvement from 10 to 26 with no subsequent exacerbations. Treatment was well-tolerated, with only mild conjunctivitis or transient hypereosinophilia reported. Notably, skin infections resolved, and no systemic or opportunistic infections were observed. Conclusion Dupilumab is a safe and highly effective therapeutic option for pediatric patients with IEI-associated atopic manifestations, improving clinical outcomes, quality of life, and infection profile while preserving immune function. These findings support broader application of dupilumab in patients with IEI and warrant further investigation in larger, multicenter studies.
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