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ASH 2026 Guidelines for Management of Relapsed/Refractory Disease in Adolescents and Young Adults with ALL.

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O'Dwyer KM, Winestone LE, Cheung MC, Benitez L, Buldini B, Cole PD

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[BACKGROUND] Adolescents and young adults (AYA) with relapsed or refractory acute lymphoblastic leukemia (ALL) face unique challenges as they experience greater treatment resistance, higher rates of t

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APA O'Dwyer KM, Winestone LE, et al. (2026). ASH 2026 Guidelines for Management of Relapsed/Refractory Disease in Adolescents and Young Adults with ALL.. Blood advances. https://doi.org/10.1182/bloodadvances.2021006479
MLA O'Dwyer KM, et al.. "ASH 2026 Guidelines for Management of Relapsed/Refractory Disease in Adolescents and Young Adults with ALL.." Blood advances, 2026.
PMID 41670624 ↗

Abstract

[BACKGROUND] Adolescents and young adults (AYA) with relapsed or refractory acute lymphoblastic leukemia (ALL) face unique challenges as they experience greater treatment resistance, higher rates of toxicity, and present at a specific life stage with distinct priorities.

[OBJECTIVE] These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support clinicians, patients, and other health care professionals in their decisions about management of AYAs with relapsed/refractory ALL.

[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 eight recommendations and one research-only recommendation, covering remission re-induction and consolidation. They focused on the following treatment modalities: immunotherapy, targeted therapies, allogeneic hematopoietic stem cell transplantation (allo-HSCT), and central nervous system (CNS)-directed therapy.

[CONCLUSIONS] Key recommendations include the use of blinatumomab and/or inotuzumab over chemotherapy for re-induction. Additional management of ALL subsets (T-ALL), CNS relapse, and the role of consolidation with allogeneic transplantation are addressed. Future research should evaluate these approaches with special attention to the unique AYA population and should evaluate quality of life outcomes.

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