American Society of Hematology 2026 guidelines for the diagnosis and management of severe and very severe acquired aplastic anemia

BACKGROUND: Aplastic anemia is a rare, life-threatening condition marked by pancytopenia and bone marrow hypocellularity. Despite therapeutic advances, clinical practice remains variable, and uncertainties persist regarding diagnosis and optimal management. To address these gaps, the American Society of Hematology (ASH) developed evidence-based guidelines to provide standardized, patient-centered recommendations. OBJECTIVE: The recommendations are intended to support patients, clinicians, and other health care professionals in their decisions about the management and diagnosis of severe and very severe immune-acquired aplastic anemia. METHODS: ASH formed a multidisciplinary guideline panel of content experts, methodologists, and a patient representative. An evidence synthesis team supported the guideline development process by conducting systematic evidence reviews. The panel prioritized clinical questions and used the grading of recommendations assessment, development, and evaluation approach, including the evidence-to-decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 33 recommendations and 4 good practice statements addressing the use of diagnostic tests, treatment strategies and supportive care. Additional recommendations covered the incorporation of eltrombopag into immunosuppressive regimens and the use of antimicrobial prophylaxis for patients at high risk. For most clinical questions, the certainty in the evidence was rated as low or very low, largely due to the reliance on small, nonrandomized studies. CONCLUSIONS: Recommendations emphasize prioritizing hematopoietic cell transplantation for younger individuals with an available matched sibling or unrelated donor and as a second-line option after failure of immunosuppressive therapy. The panel also recommended adding eltrombopag to immunosuppressive regimens and using antibiotic and antifungal prophylaxis for patients with neutropenia.