flt3 clonal evolution in patients with acute myeloid leukemia

Conditions: Acute Myeloid Leukemia

Summary: this retrospective cohort study aims to describe the current flt3 testing landscape in taiwan. it includes two patient groups: non-m3 primary aml patients with relapsed/refractory disease (r/r cohort) and newly diagnosed non-m3 primary aml patients (newly diagnosed cohort). primary objectives: estimate flt3 testing turnaround time in clinical practice. assess flt3 clonal evolution in the r/r cohort. secondary objectives: determine flt3 mutation prevalence. describe karyotypes, co-mutations, and allelic ratios in both cohorts. study european leukemianet (eln) risk in the newly diagnosed cohort. evaluate the association of flt3 mutation changes with treatment discontinuation and overall survival (os) in the r/r cohort. investigate the link between measurable residual disease (mrd) outcomes with treatment discontinuation and os in the newly diagnosed cohort. data from the national taiwan university hospital integrated medical database (ntuh-imd) and ntuh-aml dataset will be used. the index date is the earliest r/r aml evidence for the r/r cohort and the initial aml diagnosis date for the newly diagnosed cohort. a three-year baseline period will provide patient history and comorbidity information. patients will be followed until the study's end, loss to follow-up, or death.

acute myeloid leukemia (aml) is a heterogeneous group of hematological diseases. according to the taiwan cancer registry annual report, 859 new aml cases were diagnosed in taiwan in 2018, with an age-standardized incidence rate of 3.06 in males and 2.18 in females per 100,000 person-years. the fms-like tyrosine kinase 3 gene (flt3) affects the proliferation and differentiation of stem cells or hematopoietic progenitor cells. flt3 mutations are found in 25-30% of newly diagnosed aml patients and are considered a negative prognostic factor, remaining significant even after intensive chemotherapy and/or stem cell transplant. two critical issues for ensuring timely targeted therapy for flt3+ patients are the speed of flt3 test turnaround and the use of tests at key time points. rapid turnaround times are necessary for early intervention, with european leukemianet (eln) recommending results within 3 days. however, it's unclear if this is achievable in real-world settings. flt3 mutation status evolves, with 15-25% of patients losing and 13% acquiring the mutation at relapse. despite guidelines recommending flt3 testing at diagnosis and relapse, there is no consensus in taiwan on its importance and timing. some observational studies on aml in taiwan have been conducted but provide limited information on the timing and turnaround of flt3 testing in real-world practice. this study will describe the current flt3 testing landscape, including turnaround time and timing of tests among adult relapsed/refractory (r/r) aml patients at ntuh. it will also investigate the clinical characteristics and survival outcomes of both adult r/r aml and newly diagnosed aml patients.

Eligibility criteria:
inclusion criteria: * relapsed/refractory cohort: 1. adult patient (age ≥18 years) diagnosed with non-m3 primary aml (confirmed diagnosis using who 2016 criteria within the ntuh-aml dataset) who: * first experienced refractory disease (failure to achieve complete remission or complete remission with incomplete hematologic recovery) to 2 cycles of induction therapy between 1 january 2009 and 31 december 2019, or * first experienced hematological relapse after a cr between 1 january 2009 and 31 december 2019. patient with bone marrow blasts ≥5 %, reappearance of blasts in the blood, or development of extramedullary disease after achieving remission is defined to have relapse of aml. * newly diagnosed cohort: 1. adult patient (age ≥ 18 years) newly diagnosed with non-m3 primary aml (confirmed diagnosis using who 2016 criteria within the ntuh-aml dataset) between 1 january 2009 and 31 december 2019. exclusion criteria: * relapsed/refractory cohort: 1. patient with m3 subtype (acute promyelocytic leukemia, apl) 2. patient with prior history of myelodysplastic syndrome (mds) or myeloproliferative neoplasms (mpn) 3. patient without any flt3 records 4. patient with secondary or therapy-related aml * newly diagnosed cohort: 1. patient with m3 subtype (apl) 2. patient with prior history of mds or mpn 3. patient without any flt3 records 4. patient with secondary or therapy-related aml

Keywords: acute myeloid leukemia flt3 clonal evolution