Upfront alternative donor HCT in patients with SAA may help fill current treatment paradigm gaps

January 2026

Patients with severe aplastic anemia (SAA) conventionally receive immunosuppressive therapy (IST) as a first-line treatment. This approach has limited long-term effectiveness and carries a risk of complications like secondary malignancies. The use of allogeneic hematopoietic cell transplantation (HCT) for treatment of SAA has increased in recent years.

Background

Most studies of HCT outcomes in SAA patients have focused on recipients of matched sibling donor (MSD) HCT. The use of HCT from alternative donors (haploidentical, mismatched unrelated or matched unrelated, as defined in the study) has historically been limited by transplant-related complications, including graft-versus-host disease (GVHD). Recent advances—particularly the use of post-transplant cyclophosphamide (PTCy) for GVHD prevention—have improved outcomes for patients lacking a matched donor.

Methods

The authors of this review aimed to summarize the current SAA treatment landscape, highlight gaps where more research is needed, and assess where upfront alternative donor HCT can help fill these gaps and bridge access to HCT for patients without an MRD. They also discuss how to drive meaningful changes in SAA treatment with proactive integration of stakeholder engagement and an implementation framework.

Results

Results were discussed across four major topics:

Key topic
Discussion
Strengths and shortcomings of current treatment approaches in treatment-naïve severe aplastic anemia (TN SAA)
  • Recent drug additions like eltrombopag improve responses modestly but lack durability
  • Access for older or racially diverse patients lacking matched donors remains limited, with evolving strategies like RIC and PTCy helping to address these disparities
Alternative donor HCT in patients with SAA
  • Trials for HCT with haploidentical donors have demonstrated feasibility in diverse and older patient populations, with encouraging results in treatment-naïve SAA, prompting reconsideration of traditional IST-first strategies
  • Despite promising data, current guideline support for upfront alternative donor HCT remains conditional due to the lack of high-quality, multicenter trial evidence
The role of stakeholder engagement and implementation framework
  • Translation of clinical trial findings into routine practice remains inconsistent
  • Active stakeholder engagement and integration of implementation science frameworks (e.g., BMT CTN’s Dissemination and Implementation Committee) are increasingly prioritized in trial design and execution
Current clinical trials' potential to influence clinical practice for TN SAA
  • Two major multicenter trials—CureAA (BMT CTN 2207) and TransIT (BMT CTN 2202)—are testing the use of upfront alternative donor HCT in treatment-naïve SAA, aiming to expand access, especially for older patients or those without matched related donors, and comparing it directly to standard IST in younger patients

Key takeaways

The treatment landscape for SAA has improved significantly due to global research efforts, with HCT now widely accepted for treatment-naïve patients. However, challenges such as limited donor availability and age-related barriers persist. Ongoing research aims to enhance IST and expand access to HCT, with future progress depending on strong stakeholder engagement and implementation strategies. Consideration of upfront alternative donor HCT in these patients may help address access disparities for patients without a matched related donor.

Patients with SAA can contact the Jason Carter Clinical Trials Search and Support Program to get personalized help from a clinical trials navigator to discover trials they may be eligible for. If they are an alloHCT candidate, they can also reach out to our NMDPSM Patient Support Center to learn about other resources and support to help them overcome barriers to treatment. Support is also available in Spanish.

Figure

This figure illustrates the current treatment paradigm for patients with SAA.
The current treatment paradigm for patients with SAA.
MSD = matched sibling donor

Bhatt N, et al., published in Blood Advances