Abstract
Simple SummaryAround 50% of patients with acute myeloid leukemia (AML) achieve a definite cure with intensive chemotherapy and consolidation, but relapse remains the main cause of death. Clonal hematopoiesis (CH) describes the presence of a clonal subset of myeloid precursors without known hematologic disease. We aimed to investigate whether the presence of CH-related mutations in the three most common genes (DNMT3A, TET2, and ASXL1, called DTA mutations) after autologous stem cell transplantation (ASCT) influence the outcome and retrospectively analyzed samples of 110 AML patients. We found no significant impact from the presence of DTA-CH on progression-free or overall survival. Thus, the persistence of DTA mutations after induction treatment should not prevent AML patients in first remission from ASCT consolidation. These results should undergo verification in independent cohorts. Introduction: Despite a 50% cure rate, relapse remains the main cause of death in patients with acute myeloid leukemia (AML) consolidated with autologous stem cell transplantation (ASCT) in first remission (CR1). Clonal hematopoiesis of indeterminate potential (CH) increases the risk for hematological and cardiovascular disorders and death. The impact of CH persisting after ASCT in AML patients is unclear. Materials and Methods: We retrospectively investigated the prognostic value of persisting DNMT3A, TET2, or ASXL1 (DTA) mutations after ASCT. Patients underwent stratification depending on the presence of DTA mutations. Results: We investigated 110 consecutive AML patients receiving ASCT in CR1 after two induction cycles at our center between 2007 and 2020. CH-related mutations were present in 31 patients (28.2%) after ASCT. The baseline characteristics were similar between patients with or without persisting DTA mutations after ASCT. The median progression free survival was 26.9 months in patients without DTA mutations and 16.7 months in patients with DTA mutations (HR 0.75 (0.42–1.33), p = 0.287), and the median overall survival was 80.9 and 54.4 months (HR 0.79 (0.41–1.51), p = 0.440), respectively. Conclusion: We suggest that DTA-CH after ASCT is not associated with an increased risk of relapse or death. The persistence of DTA mutations after induction should not prevent AML patients in CR1 from ASCT consolidation. Independent studies should confirm these data.
Highlights
Despite a 50% cure rate, relapse remains the main cause of death in patients with acute myeloid leukemia (AML) consolidated with autologous stem cell transplantation (ASCT)in first remission (CR1)
We investigated the impact on the survival rates by applying 5% and 10% variant allele frequency (VAF) cutoffs for the clonal hematopoiesis (CH) DTA mutations
While the impact of CH on the risk of disease development has been intensively studied, less data are available on the impact of DTA mutations during complete remission and, to the best of our knowledge, no previous study has investigated the prognostic impact of CH for patients undergoing high-dose chemotherapy (HDCT) or ASCT for AML in CR1
Summary
Despite a 50% cure rate, relapse remains the main cause of death in patients with acute myeloid leukemia (AML) consolidated with autologous stem cell transplantation (ASCT)in first remission (CR1). Despite a 50% cure rate, relapse remains the main cause of death in patients with acute myeloid leukemia (AML) consolidated with autologous stem cell transplantation (ASCT). Materials and Methods: We retrospectively investigated the prognostic value of persisting DNMT3A, TET2, or ASXL1 (DTA) mutations after ASCT. Patients with acute myeloid leukemia (AML) considered fit for intensive treatment are treated with one or two cycles of intensive induction chemotherapy, followed by consolidation with either additional chemotherapy cycles along with autologous or allogeneic hematopoietic stem cell transplantation. The stratification of patients for these consolidation treatment options relies on the genetic risk assessed by cytogenetics and molecular analyses at initial diagnosis, the response to induction treatment, and the morbidity and mortality associated with the treatment options [1,2]. The detection of druggable mutations has opened the door for customized treatment strategies, some of which were integrated in the European LeukemiaNet (ELN) risk assessment and treatment for patients with AML [1,6,7]
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