ASH 2026 guidelines: First-line management of AYA patients with ALL

American Society of Hematology (ASH) 2026 guidelines for the first-line management of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) were published in Blood Advances by DuVall et al. These evidence-based guidelines provide 15 recommendations for newly diagnosed (ND) B-cell or T-cell ALL (B-ALL/T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). 

Key data: The panel strongly recommends pediatric-inspired, asparaginase-containing regimens over traditional adult-inspired protocols for first-line therapy in AYA ALL; prophylactic premedication is recommended to prevent hypersensitivity, and empiric asparaginase dose capping and reductions are suggested to mitigate toxicity while preserving efficacy. It is recommended that patients on these regimens switch to an Erwinia-based asparaginase formulation rather than discontinuing therapy if they develop an asparaginase-related hypersensitivity. The panel recommends against routine prophylactic use of cryoprecipitate or fibrinogen concentrate (unless active bleeding occurs) and against routine use of unfractionated heparin to prevent venous thromboembolism with these regimens. Routine allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) is not recommended, but there may be a survival benefit for higher-risk subgroups. Good practice statements deemed to have unequivocal net benefit are also provided.  

Key learning: The ASH 2026 guidelines provide 15 key clinical recommendations and multiple good practice statements for the first-line treatment of AYA ALL, with pediatric-inspired, asparaginase-based regimens considered the preferred first-line approach in this patient population.