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- Title
WT1 Expression Is Associated with Poor Overall Survival after Azacytidine and DLI in a Cohort of Adult AML and MDS Patients.
- Authors
Aydin, Semra; Schmitz, Jennifer; Dellacasa, Chiara M.; Dogliotti, Irene; Giaccone, Luisa; Busca, Alessandro
- Abstract
Simple Summary: Azacytidine and donor lymphocyte infusions were combined effectively in a single-center high-risk patient cohort (n = 29) for post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome. Bone marrow Wilms tumor gene 1 (WT1) expression was measured at time of transplant and post-transplant relapse. By using the Cox proportional hazards model, cut-off values for WT1 at both time points were obtained. The disease risk index incorporating initial cytogenetics and the disease stage at transplant as well as WT1 expression was significantly associated with overall survival, indicating that WT1 may represent a minimal residual disease marker in this context of cell therapy response evaluation, especially in high-risk patients currently considered to be in complete remission. Cut-off values for bone marrow WT1 expression for the two decisive treatment time points were proposed. Introduction: Post-transplant relapse of acute myeloid leukemia and myelodysplastic syndrome faces restricted effective salvage regimens. We retrospectively analyzed the use of Azacitidine–donor lymphocyte infusion (AZA/DLI) in this setting. Furthermore, data on bone marrow Wilms tumor gene 1 (WT1) expression were collected. Methods: A Cox proportional hazards model, an outcome-oriented approach for the lowest smoothed plot of the martingale residuals, was performed for the cut-point determination of the respective WT1 expression levels. Finally, a Cox proportional hazards model investigated the association of overall survival (OS) with predictors. Results: An overall response of 41.4% with a median duration of 11.9 months for stable disease and 19.5 months for complete response (CR) patients was achieved. The disease risk index (DRI) high-/very high-risk patients had a shorter OS of 4.4 months than intermediate-risk patients, with 14.5 months, p = 0.007. At transplant, WT1-overexpressing patients (>150 copies) had a shorter median OS of 5.3 months than low-WT1-expressing ones, with 13.5 months, p = 0.024. Furthermore, patients with ≤1000 WT1 copies at relapse had a significantly longer OS with 15.3 months than patients overexpressing WT1, with 4.4 months, p = 0.0002. Conclusions: DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk.
- Subjects
MYELODYSPLASTIC syndromes; RED blood cell transfusion; RISK assessment; CYTOGENETICS; AZACITIDINE; BONE marrow cancer; PATHOLOGIC complete response; CANCER patients; DESCRIPTIVE statistics; CELLULAR therapy; TUMOR markers; LONGITUDINAL method; ONCOGENES; NEPHROBLASTOMA; COMPARATIVE studies; CARCINOGENESIS; DISEASE relapse; PROPORTIONAL hazards models; OVERALL survival; DISEASE risk factors; ADULTS
- Publication
Cancers, 2024, Vol 16, Issue 17, p3070
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16173070