ASTCT guidelines for HCT in severe aplastic anemia expand eligibility and donor options

December 2024

Given numerous recent advances in allogeneic hematopoietic cell transplant (alloHCT), a panel of severe aplastic anemia (SAA) experts issued updated consensus recommendations for alloHCT in this population. Most notably, these evidence-based guidelines from the American Society for Transplantation and Cellular Therapy (ASTCT) move away from the historical age cutoff of 40 years, expanding eligibility to older adults. They also suggest prioritizing matched unrelated donors (MUD) or haploidentical donors over non-transplant immunosuppressive therapies for patients without a matched related donor (MRD). These recommendations have the potential to change referral and transplant practices for SAA.

SAA is the most common non-malignant indication for alloHCT in adults. Historically, age, neutrophil count, comorbidities and donor availability have guided initial treatment decisions in SAA. In recent years, advances in conditioning regimens, graft-versus-host disease (GVHD) prophylaxis and supportive care have made it possible for previously ineligible patients to receive HCT. These updated guidelines review the evidence for HCT in SAA, offer treatment recommendations and identify areas for future research.

A panel of transplant physicians and hematologists used the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach to conduct mini systematic reviews and meta-analyses of relevant research. They evaluated quality and risk of bias of randomized and nonrandomized studies published through December 2023. Updated recommendations were accepted upon 80% consensus across panel members, issuing good practice statements where data was insufficient.

Notable recommendations that could change practice around HCT in SAA include:

• Removing the historical age cutoff of 40 years for HCT candidacy due to advances in supportive care and conditioning; older patients may be considered for upfront HCT
• Bone marrow as the preferred graft source and rabbit ATG over horse ATG as the preferred HCT conditioning regimen
• Fludarabine-containing regimens for high-risk patients and those receiving MUD or haploidentical transplants
• Either calcineurin inhibitor (CNI) + methotrexate or post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis for MRD or MUD transplant recipients
• Prioritizing MUD or haploidentical donors over immunosuppressive therapy for patients without a MRD

These updated evidence-based guidelines reflect significant advancement in transplant eligibility and strategies for SAA. By relaxing age restrictions and expanding the definition of suitable donor types, the recommendations broaden the role of HCT as a potentially curative option for more patients with SAA. Furthermore, an updated treatment algorithm helps guide decision-making around HCT in SAA. Future research needs in SAA include optimizing GVHD prophylaxis, donor choice and post-transplant care.

Iftikhar R, et al., published in Transplantation and Cellular Therapy