https://orcid.org/0000-0002-6352-9740
Key Points
Omitting conditioning or GVHD prophylaxis in patients with typical SCID receiving MSD HCT had no impact on OS, EFS or rates of GVHD
Outcomes after MSD HCT are better for patients without active infection therefore it is optimal to proceed with MSD HCT as early as possible
The Primary Immune Deficiency Treatment Consortium (PIDTC) 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 SCID patients 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 (OS) 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 leaky SCID or Omenn syndrome patients. 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 impacted by development of grade II-IV or III-IV acute GVHD. Conditioning did not impact T or B cell reconstitution. Our data suggest omitting conditioning and GVHD prophylaxis for patients with typical SCID did not negatively impact 5-year outcomes following MSD HCT, but the data are insufficient to recommend this approach for best long-term outcomes. (ClinicalTrials.gov NCT01186913)
