The Role of Second Hematopoietic Cell Transplantation (HCT2) in Patients with Severe Combined Immunodeficiency (SCID): A Report from the Primary Immune Deficiency Treatment Consortium (PIDTC)

Transplantation and Cellular Therapy · 2025-02-01 · 1 citations

Outcomes following matched sibling donor transplantation for severe combined immunodeficiency: a report from the PIDTC

Blood Advances · 2025-11-25

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.

T-cell Exhaustion In Patients With Severe Combined Immunodeficiency Transplanted Without Conditioning OR Graft Versus Host Disease Prophylaxis

Journal of Allergy and Clinical Immunology · 2025-02-01

Treatment with Elapegademase Restores Immunity in Infants with Adenosine Deaminase Deficient Severe Combined Immunodeficiency

Journal of Clinical Immunology · 2024-04-27 · 8 citations

PURPOSE: Patients with adenosine deaminase 1 deficient severe combined immunodeficiency (ADA-SCID) are initially treated with enzyme replacement therapy (ERT) with polyethylene glycol-modified (PEGylated) ADA while awaiting definitive treatment with hematopoietic stem cell transplant (HSCT) or gene therapy. Beginning in 1990, ERT was performed with PEGylated bovine intestinal ADA (ADAGEN®). In 2019, a PEGylated recombinant bovine ADA (Revcovi®) replaced ADAGEN following studies in older patients previously treated with ADAGEN for many years. There are limited longitudinal data on ERT-naïve newborns treated with Revcovi. METHODS: We report our clinical experience with Revcovi as initial bridge therapy in three newly diagnosed infants with ADA-SCID, along with comprehensive biochemical and immunologic data. RESULTS: Revcovi was initiated at twice weekly dosing (0.2 mg/kg intramuscularly), and monitored by following plasma ADA activity and the concentration of total deoxyadenosine nucleotides (dAXP) in erythrocytes. All patients rapidly achieved a biochemically effective level of plasma ADA activity, and red cell dAXP were eliminated within 2-3 months. Two patients reconstituted B-cells and NK-cells within the first month of ERT, followed by naive T-cells one month later. The third patient reconstituted all lymphocyte subsets within the first month of ERT. One patient experienced declining lymphocyte counts with improvement following Revcovi dose escalation. Two patients developed early, self-resolving thrombocytosis, but no thromboembolic events occurred. CONCLUSION: Revcovi was safe and effective as initial therapy to restore immune function in these newly diagnosed infants with ADA-SCID, however, time course and degree of reconstitution varied. Revcovi dose may need to be optimized based on immune reconstitution, clinical status, and biochemical data.

Improving Compliance with State-Recommended Guidelines for Severe Combined Immunodeficiency (SCID) Newborn Screening (NBS) in the Intensive Care Nursery (ICN)

Journal of Allergy and Clinical Immunology · 2024-02-01

106 Outcomes Following Hematopoietic Cell Transplant for CD3δ Severe Combined Immune Deficiency: a PIDTC Natural History Study

Clinical Immunology · 2024-04-23

Outcomes Following Matched Sibling Donor Transplant for Severe Combined Immunodeficiency: A Report from the Pidtc

Transplantation and Cellular Therapy · 2024-02-01 · 3 citations

Relevance of lymphocyte proliferation to PHA in severe combined immunodeficiency (SCID) and T cell lymphopenia

Clinical Immunology · 2024-02-15 · 6 citations

Abstract 1335: Natural history of biomarker changes associated with gut inflammatory disease in postnatal human development

Journal of Biological Chemistry · 2023-01-01

Newborn screening has improved the survival of infants with severe combined immunodeficiency (SCID) – a Primary Immune Deficiency Treatment Consortium (PIDTC) study

Clinical Immunology · 2023-05-01 · 2 citations