Weekly Metronomic Venetoclax and Decitabine/Cedazuridine in Acute Myeloid Leukemia Patient Declining Blood Transfusion

Introduction: Acute myeloid leukemia (AML) treatment typically involves intensive chemotherapy associated with prolonged cytopenias and frequent transfusion requirements. Patients who decline blood products, such as Jehovah’s Witnesses (JW), present a therapeutic challenge, as transfusion support is integral to standard care. Emerging low-intensity regimens combining venetoclax (VEN) with hypomethylating agents (HMA) offer a potential alternative with reduced myelosuppression. Case Presentation: A 77-year-old male JW with AML with myelodysplastic syndrome–related changes (MRC) and mutations in DDX41, ASXL1, and PPM1D presented with pancytopenia. Due to refusal of transfusions, he was treated with a metronomic, all-oral regimen of VEN 400 mg weekly and decitabine/cedazuridine (DEC-C) 35/100 mg weekly, supported by erythropoiesis-stimulating agent (darbepoetin alfa) and thrombopoietin agonist (romiplostim) as needed. After 4 weeks, bone marrow blasts decreased from 20–25% to 10%, with clearance of ASXL1 and PPM1D mutations and reduction of DDX41 variant allele frequency (VAF) to 2.9% from 9.7%. At 26 weeks, marrow blasts further decreased to 5%, DDX41 VAF remained low (2.6%), and counts normalized (ANC 1.73 × 10³/µL, Hb 13.1 g/dL, PLT 256 × 10³/µL) without any transfusions. Conclusion: This case demonstrates that a metronomic, all-oral VEN and DEC-C regimen can achieve hematologic improvement and molecular response in AML while maintaining transfusion independence. It highlights a feasible and safe therapeutic option for patients declining blood products, achieving disease control with minimal toxicity.