Cancers · 2026
Clinical Impact of the CTLA4 rs231775 Polymorphism in Acute Myeloid Leukemia Treated with Autologous Stem Cell Transplantation.
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Tarozzi Elisa, Seipel Katja, Shaforostova Inna, Kronig Marie-Noelle, Bacher Ulrike, Pabst Thomas
Аннотация
BACKGROUND: Germline variants of the immune checkpoint receptor CTLA4 may modulate T-cell activation, potentially influencing post-transplant immune reconstitution and clinical outcomes.
METHODS: In this retrospective single-center study, 140 AML patients who underwent ASCT were stratified into three groups according to the CTLA4 rs231775 geno-types A17hom, T17Ahet, and T17hom. Clinical outcomes, including overall survival (OS) and progression-free survival (PFS), were evaluated. Multivariate analysis was performed to adjust for known prognostic covariates.
RESULTS: Baseline clinical characteristics varied according to CTLA4 genotype with a higher proportion of favorable cytogenetic risk in A17hom carriers. Comparative analysis revealed differences in survival rates, with superior outcomes in A17hom carriers. In multivariate analysis directional trends persisted across all endpoints.
CONCLUSION: The prognostic impact of CTLA4 rs231775 on post-ASCT outcomes suggests that T-cell inhibitory signaling may contribute to anti-leukemic immune surveillance in the autologous setting. These findings provide a rationale for investigating CTLA4 inhibition as consolidation therapy following ASCT in future prospective studies, particularly in T17hom carriers, who may harbor a less favorable immune profile. CTLA4 genotyping at diagnosis may represent a practical tool to support risk stratification in AML.
METHODS: In this retrospective single-center study, 140 AML patients who underwent ASCT were stratified into three groups according to the CTLA4 rs231775 geno-types A17hom, T17Ahet, and T17hom. Clinical outcomes, including overall survival (OS) and progression-free survival (PFS), were evaluated. Multivariate analysis was performed to adjust for known prognostic covariates.
RESULTS: Baseline clinical characteristics varied according to CTLA4 genotype with a higher proportion of favorable cytogenetic risk in A17hom carriers. Comparative analysis revealed differences in survival rates, with superior outcomes in A17hom carriers. In multivariate analysis directional trends persisted across all endpoints.
CONCLUSION: The prognostic impact of CTLA4 rs231775 on post-ASCT outcomes suggests that T-cell inhibitory signaling may contribute to anti-leukemic immune surveillance in the autologous setting. These findings provide a rationale for investigating CTLA4 inhibition as consolidation therapy following ASCT in future prospective studies, particularly in T17hom carriers, who may harbor a less favorable immune profile. CTLA4 genotyping at diagnosis may represent a practical tool to support risk stratification in AML.