J Allergy Clin Immunol. 2021 Oct 27:S0091-6749(21)01629-8. doi: 10.1016/j.jaci.2021.10.017. Online ahead of print.
ABSTRACT
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome.
OBJECTIVE: To perform a comprehensive multicenter analysis of genotype-specific HSCT outcome including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome.
METHODS: HSCT outcome was studied in 338 patients with genetically confirmed SCID, transplanted in 2006-2014 and registered in the SCETIDE registry. In a representative subgroup of n=152 patients data on IR and long-term clinical outcome were analyzed.
RESULTS: 2-years OS was similar with matched family and unrelated donors and superior to mismatched donor HSCT (p < 0.001). The 2-year EFS was similar in matched and mismatched unrelated donor and less favorable in mismatched related donor (MMRD) HSCT (p < 0.001). Genetic subgroups did not differ in 2-year OS (p=0.1) and EFS (p=0.073). In multivariate analysis, pretransplant infections and use of MMRD were associated with less favorable OS and EFS. With a median follow-up of 6.2 years [range 2.0-11.8 years], 73/152 IR cohort patients were alive and well without immunoglobulin dependency. IL2Rγ-JAK3-IL7R deficient SCID, myeloablative conditioning, matched donor HSCT, and naïve CD4 T lymphocytes > 0.5x10e3/μL at +1-year were identified as independent predictors of favorable clinical and immunological outcome.
CONCLUSION: Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long term outcome, treatment strategies should aim for optimal naïve CD4 T lymphocyte regeneration.
PMID:34718043 | DOI:10.1016/j.jaci.2021.10.017
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