Kristen M O'Dwyer, Lena E. Winestone, Matthew C. Cheung, Lydia L Benitez, Barbara Buldini, Peter D. Cole, Moussab Damlaj, Bhagirathbhai Dholaria, Ajoy Dias, Alexander T. Dils, Michelle Fritsch, John P. Greer, Brandon Hayes-Lattin, Meret Henry, Aaron Jaffe, Omer Jamy, Partow Kebriaei, Ilayna Mehrtens, Nirali N Shah, Lindsay Wilde, Patricia A. Young, Htun Ja, Ghid Kanaan, Yuliia Sereda, Ian J Saldanha, Ethan M. Balk, Sumit Gupta
BACKGROUND: Adolescents and young adults (AYAs) with relapsed/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 8 recommendations and 1 research-only recommendation, covering remission reinduction and consolidation. They focused on the following treatment modalities: immunotherapy, targeted therapies, allogeneic hematopoietic stem cell transplant, and central nervous system (CNS)-directed therapy. CONCLUSIONS: Key recommendations include the use of blinatumomab and/or inotuzumab over chemotherapy for reinduction. Additional management of ALL subsets (T-cell ALL), CNS relapse, and the role of consolidation with allogeneic transplant are addressed. Future research should evaluate these approaches with special attention to the unique AYA population, and should evaluate quality of life outcomes.