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Current treatments for acute myeloid leukemias (AMLs) cure fewer than 30 % of patients. This low efficacy is due, in part, to the inter-patient and intra-patient heterogeneity of AMLs; accordingly, all current AML treatment regimens involve drug combinations (polypharmacy). A recently-completed clinical trial in relapsed/refractory AML using a combination of two newer targeted antileukemics, the BCL-2 inhibitor venetoclax (VEN) plus the FLT3 inhibitor gilteritinib (GIL), yielded highly promising results for this two-drug polypharmacy combination.

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Objective: To retrospectively analyze the incidence of infections in elderly acute myeloid leukemia (AML) patients undergoing induction therapy with venetoclax combined with hypomethylating agents and to compare these findings with those from patients receiving standard or low-dose chemotherapy.

Methods: Medical records of 169 elderly (≥60 years old) AML patients diagnosed via MICM (morphology, immunology, cytogenetics, and molecular genetics) at the First Affiliated Hospital of USTC between June 2019 and June 2022 were reviewed. Patients were divided into three groups: venetoclax combined with hypomethylating agents group (targeted therapy group), standard chemotherapy group, and low-dose chemotherapy group.

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Induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells offer an opportunity for a standardized, off-the-shelf treatment with the potential to treat a wider population of acute myeloid leukaemia (AML) patients than the current standard of care. FT538 iPSC-NKs express a high-affinity, noncleavable CD16 to maximize antibody dependent cellular cytotoxicity, a CD38 knockout to improve metabolic fitness, and an IL-15/IL-15 receptor fusion preventing the need for cytokine administration, the main source of adverse effects in NK cell-based therapies. Here, we sought to evaluate the potential of FT538 iPSC-NKs as a therapy for AML through their effect on AML cell lines and primary AML cells.

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As median age of patients with acute myeloid leukemia is 72 years, older patients continue to be a vulnerable cohort representing significant challenges in clinical practice. Patient-specific comorbidities as well as leukemia-specific unfavorable molecular- and cytogenetics confer even poorer outcomes. Treatment of AML therefore needs to be less toxic to prevent harm while lowering or eradicating leukemic burden to prolong survival.

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