Clinical strategies for leukemia management: Recommendations from the Bridging the Gaps in Hematology Oncology Consensus Conference 2025.

Rapid progress in leukemia management has increased treatment complexity, resulting in clinical scenarios not fully addressed by standard guidelines. To provide expert guidance, the Bridging the Gaps in Hematology Consensus Conference reunited U.S.-based experts in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and acute lymphoblastic leukemia (ALL) on February 25-26, 2025. Key consensus recommendations were established across AML, MDS, and ALL. For AML, consensus favored CPX-351 for fit patients with secondary or therapy-related AML, without access to clinical trials, and prioritized clinical trial enrollment for other specific molecular subtypes, including those eligible for menin inhibitors. In MDS, consensus supported moving to a harmonized World Health Organization/International Consensus Classification, diagnosing AML based on genetic markers in conjunction with blast counts, and prioritizing stem cell transplant (HSCT) for high-risk patients regardless of response to hypomethylating therapy, particularly for multi-hit TP53-mutated MDS. For ALL, recommendations highlighted avoiding transplant in most Philadelphia chromosome-positive patients achieving minimal residual disease (MRD)-negativity by noting the high relapse risk with certain IKZF1, CDKN2A/B, and PAX5 aberrations, and administering blinatumomab regardless of MRD status in Philadelphia chromosome-positive and -negative ALL. Areas lacking consensus were also identified, highlighting the need for further research. Future directions include refining treatment sequencing, improving outcomes for high-risk subtypes, evaluating the role of HSCT in the era of novel therapies, and standardizing MRD assessment. This consensus report provides valuable expert insights to inform clinical practice and guide future research in leukemia.