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

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 offer a potential alternative with reduced myelosuppression.

A 77-year-old male JW with AML with myelodysplastic syndrome-related changes 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, hemoglobin 13.1 g/dL, PLT 256 × 10³/µL) without any transfusions.

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.