University of Miami/Sylvester Cancer Center, Miami, FL
Muhammad Husnain , Krishna Komanduri , Jeremy Ramdial , Lazaros J. Lekakis , Trent Peng Wang , Mark Goodman , Denise L. Pereira , Amer Beitinjaneh , Douglas Carollo , Robert Ali , Yaqub Nadeem Mohammed , Junaid Arshad , Diana Byrnes , Eduardo Edelman Saul , Luis E. Aguirre , Antonio Martin Jimenez
Background: Allogeneic Stem Cell Transplant (alloSCT) continues to be the optimal consolidation strategy for many patients with AML; cytogenetic and molecular abnormalities are known predictors of post-transplant outcomes. There is increasing evidence that Molecular Minimal Residual Disease (MMRD) following induction has important prognostic implications and its value in the prediction of post-transplant relapse continues to be elucidated. We aim to evaluate the impact of genetics and pre-transplant MMRD on clinical outcomes following alloSCT. Methods: We retrospectively evaluated eighty-nine patients, ≥18 years with a diagnosis of AML in complete morphologic remission (i.e. < 5% BM blasts by morphologic assessment) who received alloSCT between 01/2012-05/2018 at the University of Miami and for whom cytogenetic and comprehensive molecular data was available prior to transplantation. Patients were stratified into favorable, intermediate and poor-risk categories based on 2017 ELN criteria. MMRD was defined as persistent leukemia-specific mutations prior to transplantation (i.e. NPM1, FLT3, CEBPA, IDH1-2, RUNX1 and TP53). Persistence of DTA mutations (DNMT3A, TET2 and ASXL1) was not considered MMRD, patients with unavailable cytogenetic/molecular data at diagnosis were excluded. Results: Seventy-four (83%) patients were transplanted in CR1, myeloablative conditioning was used in 72% of patients. Two-year OS and LFS were 69.4% and 78.2%, respectively. Stratification by ELN criteria resulted in prognostic separation for patients transplanted in CR1: 2-year OS for favorable (87%), intermediate (68%) and adverse risk (51%) patients (p = 0.0417). The presence of MMRD was the strongest predictor of post-transplant outcomes for the whole cohort with 2-year OS and LFS of 29.4% and 37.1% (HR 5.45 [95%CI 2.43-12.3] p = 0.0001; HR 12.4 [95%CI: 3.76 to 39.8] p = 0.0001); respectively. Subgroup analysis confirmed that MMRD was associated with significantly inferior LFS for IM/favorable and adverse risk patients (HR: 6.76 [95% CI 1.12 to 40.9], p = 0.038). Conclusions: Pre-transplant MMRD was the most important prognostic factor for relapse and survival in our cohort of AML patients undergoing alloSCT. Correlation of MMRD with other transplant variables such as conditioning intensity, MRD status by MFC and the impact of pre-emptive/therapeutic strategies in high-risk patients continues to be explored.
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Abstract Disclosures
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