American Society of Hematology 2026 guidelines for frontline management of acute lymphoblastic leukemia in adolescents and young adults

BACKGROUND: Adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) represent a unique population. Treatment regimens can vary significantly depending on whether they receive care in a pediatric or in an adult setting. They also have distinctive care needs, social risk factors, and disease behavior compared with other age groups. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about the frontline management of ALL in AYAs. METHODS: ASH formed a multidisciplinary guideline panel including hematologists, AYA psychosocial care specialists, pharmacists, methodologists, and patient representatives with efforts to minimize bias from conflicts of interest. An evidence review team at Brown University supported guideline development, including performing systematic evidence reviews up to November 2023. The panel prioritized clinical questions and outcomes according to importance for clinicians and patients. The panel used grading of recommendations assessment, development, and evaluation (GRADE), including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 15 recommendations and several good practice statements. CONCLUSIONS: Pediatric-inspired regimens containing asparaginase are recommended as frontline therapy compared with more traditional adult-inspired protocols, requiring significant supportive care and close follow-up. Allogeneic hematopoietic stem cell transplantation is not routinely recommended in first remission but may be indicated for higher-risk subsets or those with suboptimal responses to initial therapy. The use of targeted agents in frontline therapy is increasingly supported, although further research is needed to optimize this strategy.