Older Jehovah’s Witnesses with Acute Myeloid Leukemia: Hypomethylating Agents and Venetoclax as a Transfusion-Sparing Approach

The treatment of acute myeloid leukemia (AML) in Jehovah’s Witness (JW) patients poses unique challenges due to their refusal of blood transfusions. This case series reports the outcomes of four older JW patients with AML treated with azacitidine (Aza) and venetoclax (Ven), including two with hyperleukocytosis and FLT3-ITD mutations. Three patients achieved initial remission; one of these patients subsequently received gilteritinib in combination with Ven and Aza, also achieving remission. All but one therapy cycle was administered in an outpatient setting, and hematologic recovery occurred in all patients without bleeding, ischemic events, or fungal infections. Three patients experienced disease relapse at 179, 301, and 392 days post-diagnosis, while one patient remains alive 706 days post-diagnosis. This report is among the first to demonstrate that Ven and Aza can safely achieve remissions, some of which were durable, in older JW patients with AML, even those with proliferative features like hyperleukocytosis and FLT3-ITD mutations. Our central finding is that Ven and Aza represent safe and effective transfusion-sparing therapeutic options in this population, with triplet therapy incorporating gilteritinib also proving feasible with dose modifications. These findings underscore the clinical relevance of such approaches, suggesting that transfusion refusal should not preclude treatment initiation, offering meaningful clinical outcomes and potentially enhancing quality of life in this population.