Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation

Abstract

Measurable residual disease (MRD) is increasingly employed as a biomarker of quality of complete remission (CR) in intensively treated acute myeloid leukemia (AML) patients. We evaluated if a MRD-driven transplant policy improved outcome as compared to a policy solely relying on a familiar donor availability. High-risk patients (adverse karyotype, FLT3-ITD) received allogeneic hematopoietic cell transplant (alloHCT) whereas for intermediate and low risk ones (CBF-AML and NPM1-mutated), alloHCT or autologous SCT was delivered depending on the post-consolidation measurable residual disease (MRD) status, as assessed by flow cytometry. For comparison, we analyzed a matched historical cohort of patients in whom alloHCT was delivered based on the sole availability of a matched sibling donor. Ten-years overall and disease-free survival were longer in the MRD-driven cohort as compared to the historical cohort (47.7% vs. 28.7%, p = 0.012 and 42.0% vs. 19.5%, p = 0.0003). The favorable impact of this MRD-driven strategy was evident for the intermediate-risk category, particularly for MRD positive patients. In the low-risk category, the significantly lower CIR of the MRD-driven cohort did not translate into a survival advantage. In conclusion, a MRD-driven transplant allocation may play a better role than the one based on the simple donor availability. This approach determines a superior outcome of intermediate-risk patients whereat in low-risk ones a careful evaluation is needed for transplant allocation.

Diagnostic Workup of Acute Myeloid Leukemia: What Is Really Necessary? An Italian Survey

“…With regard to MRD, at diagnosis, AMLs are characterized by genotypical and phenotypical features that allow leukemic cells to be distinguished from their normal counterparts (40). The leukemiaassociated immunophenotype " (LAIP) identified by multi-color flow cytometry or the "different from normal" pattern can then be used to monitor MRD (41,42). Moreover, in selected cases, such as those negative for recurrent rearrangements or NPM1 mutations, overexpression of WT1 can be considered for MRD monitoring (43)(44)(45)(46)(47)(48).…”

Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest

“…Response assessment by regular flow cytometry with a cut-off of 5% blasts is limited by its ability to detect a low level of disease, which would translate to a high rate of relapse. MRD evaluation either by flow cytometry [2] or by mutation-based analysis [3] has proved a powerful tool in the post remission induction period to evaluate deep anti-leukemia therapy efficacy, detection of early relapse, consolidation assignment (e.g., selection of transplant vs. no-transplant strategy as well as conditioning intensity), and as surrogate end-point in clinical trials [4][5][6][7][8]. Data clearly show that patients who achieve MRD negativity have a significantly longer progression free survival (PFS) and overall survival (OS) [9].…”