Characterization and prognostic significance of mitochondrial DNA variations in acute myeloid leukemia

AbstractApproximately 30% of patients with newly diagnosed acute myeloid leukemia (AML) harbor mutations in the fms-like tyrosine kinase 3 (FLT3) gene. While the adverse prognostic impact of FLT3-ITDmut in AML has been clearly proven, the prognostic significance of FLT3-TKDmut remains speculative. Current guidelines recommend rapid molecular testing for FLT3mut at diagnosis and earlier incorporation of targeted agents to achieve deeper remissions and early consideration for allogeneic stem cell transplant (ASCT). Mounting evidence suggests that FLT3mut can emerge at any timepoint in the disease spectrum emphasizing the need for repetitive mutational testing not only at diagnosis but also at each relapse. The approval of multi-kinase FLT3 inhibitor (FLT3i) midostaurin with induction therapy for newly diagnosed FLT3mut AML, and a more specific, potent FLT3i, gilteritinib as monotherapy for relapsed/refractory (R/R) FLT3mut AML have improved outcomes in patients with FLT3mut AML. Nevertheless, the short duration of remission with single-agent FLT3i’s in R/R FLT3mut AML in the absence of ASCT, limited options in patients refractory to gilteritinib therapy, and diverse primary and secondary mechanisms of resistance to different FLT3i’s remain ongoing challenges that compel the development and rapid implementation of multi-agent combinatorial or sequential therapies for FLT3mut AML.

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Prognostic Significance of Minimal/Measurable Residual Disease in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed/Refractory Acute Myeloid Leukemia

Transplantation and Cellular Therapy ◽

10.1016/s2666-6367(21)00165-2 ◽

2021 ◽

Vol 27 (3) ◽

pp. S130-S131

Author(s):

Muhammad Umair Mushtaq ◽

Alexandra M. Harrington ◽

Sibgha Gull Chaudhary ◽

Laura C. Michaelis ◽

Karen-Sue B. Carlson ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Residual Disease ◽

Prognostic Significance ◽

Hematopoietic Stem ◽

Refractory Acute Myeloid Leukemia ◽

Measurable Residual Disease ◽

Acute Myeloid

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Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1–RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1–RUNX1T1

Cancers ◽

10.3390/cancers13020336 ◽

2021 ◽

Vol 13 (2) ◽

pp. 336

Author(s):

Byung-Sik Cho ◽

Gi-June Min ◽

Sung-Soo Park ◽

Silvia Park ◽

Young-Woo Jeon ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Residual Disease ◽

Prognostic Significance ◽

Poor Survival ◽

Hematopoietic Stem ◽

Kit Mutation ◽

Time Points ◽

Post Transplant ◽

Acute Myeloid

The prognostic significance of KIT mutations and optimal thresholds and time points of measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with RUNX1-RUNX1T1 remain controversial in the setting of hematopoietic stem cell transplantation (HSCT). We retrospectively evaluated 166 high-risk patients who underwent allogeneic (Allo-HSCT, n = 112) or autologous HSCT (Auto-HSCT, n = 54). D816V KIT mutation, a subtype of exon 17 mutations, was significantly associated with post-transplant relapse and poor survival, while other types of mutations in exons 17 and 8 were not associated with post-transplant relapse. Pre- and post-transplant RUNX1–RUNX1T1 MRD assessments were useful for predicting post-transplant relapse and poor survival with a higher sensitivity at later time points. Survival analysis for each stratified group by D816V KIT mutation and pre-transplant RUNX1–RUNX1T1 MRD status demonstrated that Auto-HSCT was superior to Allo-HSCT in MRD-negative patients without D816V KIT mutation, while Allo-HSCT was superior to Auto-HSCT in MRD-negative patients with D816V KIT mutation. Very poor outcomes of pre-transplant MRD-positive patients with D816V KIT mutation suggested that this group should be treated in clinical trials. Risk stratification by both D816V KIT mutation and RUNX1–RUNX1T1 MRD status will provide a platform for decision-making or risk-adapted therapeutic approaches.

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The Prognostic Significance of IRF8 Transcripts in Adult Patients with Acute Myeloid Leukemia

PLoS ONE ◽

10.1371/journal.pone.0070812 ◽

2013 ◽

Vol 8 (8) ◽

pp. e70812 ◽

Cited By ~ 10

Author(s):

Era L. Pogosova-Agadjanyan ◽

Kenneth J. Kopecky ◽

Fabiana Ostronoff ◽

Frederick R. Appelbaum ◽

John Godwin ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Prognostic Significance ◽

Adult Patients ◽

Acute Myeloid

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A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial

Blood ◽

10.1182/blood-2010-01-267302 ◽

2010 ◽

Vol 116 (6) ◽

pp. 971-978 ◽

Cited By ~ 102

Author(s):

Christoph Röllig ◽

Christian Thiede ◽

Martin Gramatzki ◽

Walter Aulitzky ◽

Heinrich Bodenstein ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Risk Model ◽

Cox Model ◽

Prognostic Significance ◽

Disease Free Survival ◽

Intermediate Risk ◽

Npm1 Mutation ◽

Prognostic Groups ◽

Acute Myeloid

Abstract We present an analysis of prognostic factors derived from a trial in patients with acute myeloid leukemia older than 60 years. The AML96 trial included 909 patients with a median age of 67 years (range, 61-87 years). Treatment included cytarabine-based induction therapy followed by 1 consolidation. The median follow-up time for all patients is 68 months (5.7 years). A total of 454 of all 909 patients reached a complete remission (50%). Five-year overall survival (OS) and disease-free survival were 9.7% and 14%, respectively. Multivariate analyses revealed that karyotype, age, NPM1 mutation status, white blood cell count, lactate dehydrogenase, and CD34 expression were of independent prognostic significance for OS. On the basis of the multivariate Cox model, an additive risk score was developed that allowed the subdivision of the largest group of patients with an intermediate-risk karyotype into 2 groups. We are, therefore, able to distinguish 4 prognostic groups: favorable risk, good intermediate risk, adverse intermediate risk, and high risk. The corresponding 3-year OS rates were 39.5%, 30%, 10.6%, and 3.3%, respectively. The risk model allows further stratification of patients with intermediate-risk karyotype into 2 prognostic groups with implications for the therapeutic strategy. This study was registered at www.clinicaltrials.gov as #NCT00180115.

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