Broadening Donor Access in Hematopoietic Cell Transplantation Expands Equity in Clinical Trial Enrollment

Emerging data published in JAMA Network Open revealed that by expanding eligibility through mismatched unrelated donors led to significantly improved access for racially and ethnically underrepresented patients. The ACCESS trial (NCT04904588) utilized a far more diverse population (47% vs 15% and 9% in comparator cohorts) which included patients with greater socioeconomic disadvantage and financial toxicity. These data indicate that relaxing donor constraints may be a powerful lever for reducing long-standing inequities in curative cancer therapies.¹

Hematopoietic Cell Transplant and Donor Limitations

Although allogeneic hematopoietic cell transplant continues to be a potentially curative therapy for multiple high-risk hematologic malignancies—including leukemia and lymphoma—its usage has commonly been limited due to donor availability, notably the requirement for HLA-matched related or unrelated donors. Racially and ethnically minoritized patient populations are considerably less likely to identify a fully matched donor due to underrepresentation in donor registries.² This noticeable structural barrier is a persistent contributor towards disparities in transplant access and outcomes.

In recent advantages in transplant immunology—specifically post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis— the safe use of mismatched unrelated donors without compromising survival outcomes has been enabled.³ Employing these strategies expands the donor pool and signify a major shift in transplant eligibility criteria.

Broader systemic barriers remain despite these scientific advances. Patients are less likely to be offered or referred for clinical trials, have lower rates of insurance coverage, and experience greater financial toxicity during cancer treatment if they are from disadvantaged backgrounds.^4,5 This causes equitable access to curative-intent therapies such as HCT to be limited due to these intersecting barriers.

Study Overview and Key Findings

Patients undergoing first allogeneic HCT using mismatched unrelated donors with PTCy-based GVHD prophylaxis were evaluated via the ACCESS trial. The data accumulated was compared to patients undergoing a prior randomized trial, BMT CTN 1703 (NCT03959241), and a large observational cohort of allogeneic HCT recipients contributing patient-reported outcome data in routine clinical care.

The ACCESS trial demonstrated noticeably improved diversity and inclusion across 672 patients. Nearly half of the participants in the ACCESS trial identified as racially or ethnically minoritized in comparison with only 15% and 9% in comparator data.¹ It was further revealed that ACCESS participants were more likely to have Medicaid insurance, lower educational attainment, and household incomes below $40,000 annually.

ACCESS participants demonstrated higher community-level vulnerability, measured using the Social Vulnerability Index (SVI) beyond individual socioeconomic indicators. Higher SVI scores demonstrate greater neighborhood disadvantage in relation to income, housing, transportation, and employment.⁶ The indication of these findings show ACCESS enrolled patients faced both individual socioeconomic challenges and broader structural barriers to care.

Disparities were further highlighted by financial toxicity. Reports of moderate to severe financial distress following transplant amongst a substantial proportion of ACCESS participants, bringing to light the known relationship between cancer treatment intensity and economic burden.⁷ The data found that, despite this increased vulnerability, clinical trial participation remained feasible when donor eligibility was expanded.

In a geographical context, ACCESS participants lived closer to transplant centers in comparison with other cohorts. This may suggest that proximity to specialized centers continues to shape access to advanced therapies.

Clinical Implications

These data reveal that donor availability criteria are not merely a clinical constraint but also a structural determinant of equity in transplant medicine. Through expansion of eligibility to include mismatched unrelated donors, ACCESS had effectively reduced one of the most critical barriers preventing minority patients from receiving HCT.

Previous data has shown that donor availability has disproportionately limited transplant in Black and Hispanic patients due to registry underrepresentation.² Concurrently, broader oncology literature has consistently documented lower clinical trial participation among racial and ethnic minorities and low-income patients.⁴

The success in the ACCESS trial indicates modifying eligibility criteria can partially offset these systemic inequities. However, it is also of note that biomedical innovation alone is insufficient. Structural factors including referral pathways, insurance coverage, and geographic access continuously shape who benefits from curative therapies.⁸

Through analysis of the ACCESS trial, it is gathered that expanding donor eligibility through mismatched unrelated donors considerably increases racial, ethnic, and socioeconomic diversity in hematopoietic cell transplant. Clinical innovation has improved the feasibility of broader donor use; however, transplant access is continuously shaped through persistent structural inequities. These findings display the necessity of integrating clinical expertise with equity-focused care models to ensure that advances in curative therapies benefit all eligible patients.

REFERENCES

1. Cusatis R, Kou J, Bupp C, et al. Hematopoietic Cell Transplant Access and Patient Diversity. JAMA Netw Open.2026;9(5):e2610839. doi:10.1001/jamanetworkopen.2026.10839

2. Chowdhury AS, Maiers M, Spellman SR, Deshpande T, Bolon YT, Devine SM. Existence of HLA-Mismatched Unrelated Donors Closes the Gap in Donor Availability Regardless of Recipient Ancestry. Transplant Cell Ther. 2023;29(11):686.e1-686.e8. doi:10.1016/j.jtct.2023.08.014

3. Shaffer BC, Gooptu M, DeFor TE, et al. Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors. J Clin Oncol. 2024;42(28):3277-3286. doi:10.1200/JCO.24.00184

4. Pittell H, Calip GS, Pierre A, et al. Racial and ethnic inequities in US oncology clinical trial participation. JAMA Netw Open. 2023;6(7):e2322515. doi:10.1001/jamanetworkopen.2023.22515

5. Unger JM, Vaidya R, Hershman DL, Minasian LM, Fleury ME. Systematic Review and Meta-Analysis of the Magnitude of Structural, Clinical, and Physician and Patient Barriers to Cancer Clinical Trial Participation. J Natl Cancer Inst. 2019;111(3):245-255. doi:10.1093/jnci/djy221

6. Flanagan BE, Gregory EW, Hallisey EJ, et al. A social vulnerability index for disaster management. J Homel Secur Emerg Manag. 2011;8(1):1792. doi:10.2202/1547-7355.1792

7. Witte J, Mehlis K, Surmann B, et al. Methods for measuring financial toxicity after cancer diagnosis and treatment: a systematic review and its implications. Ann Oncol. 2019;30(7):1061-1070. doi:10.1093/annonc/mdz140

8. Yusuf RA, Preussler JM, Meyer CL, et al. Reducing barriers of access and care related to hematopoietic cell transplantation and cellular therapy: The mission-driven role of the national marrow donor program. Best Pract Res Clin Haematol. 2023;36(2):101480–101480. doi:10.1016/j.beha.2023.101480