Findings from the ACCESS trial support expanded use of mismatched unrelated donors in allogeneic HCT

September 2025

Historically, patients who received allogeneic hematopoietic cell transplant (alloHCT) using an HLA-mismatched donor had inferior outcomes. However, patients from ethnically and racially diverse backgrounds are less likely to find a fully matched unrelated donor on a registry. To improve outcomes of mismatched unrelated donor (MMUD) alloHCT, researchers have investigated novel graft-versus-host disease (GVHD) prophylaxis strategies such as post-transplant cyclophosphamide (PTCy) with encouraging results. The new ACCESS trial findings represent the next evolution of this research, showing that MMUD HCT is safe and effective when using peripheral blood stem cell (PBSC) grafts, expanding access to a potentially curative option for patients who don't have a fully matched donor.

An earlier clinical trial (15-MMUD) showed that MMUD alloHCT using bone marrow and PTCy for prevention of GVHD is safe and effective. These encouraging findings prompted a need to determine if this approach is safe and effective for other graft sources. Due to fewer donor collection-associated risk factors and complications compared to bone marrow, PBSC is the most frequently used graft source. The prospective, non-randomized, U.S.-based multicenter ACCESS trial evaluated PTCy-based GVHD prophylaxis for patients receiving MMUD PBSCs with myeloablative conditioning (MAC) or reduced intensity/nonmyeloablative (RIC/NMA) conditioning regimens.

Between September 2021 and August 2023, a total of 145 adults with hematological malignancies were enrolled from 21 U.S. centers. Patients received either MAC or RIC/NMA. All patients received a PBSC graft and a GVHD prophylaxis regimen of PTCy, tacrolimus and mycophenolate mofetil. Over half of the patients enrolled identified as belonging to a racial or ethnic group usually underrepresented in HCT clinical trials.

All patients received MMUD HCT, with most patients receiving a 7/8 or 6/8-matched donor (considering HLA-A, -B, -C and DRB1):

Patient characteristics: HLA match by conditioning regimen (N=145)

The study found that HCT with MMUD PBSC in the setting of PTCy-based GVHD prophylaxis results in excellent outcomes in both MAC and RIC/NMA groups, comparable to the use of fully matched donors. Results included:

• Excellent 1-year overall survival (OS) outcomes
• MAC: 83.8% (95% CI: 73.1–90.4%)
• RIC: 78.6% (95% CI: 67–86.5%)
• Effective GVHD control
• Grade 3-4 acute GVHD: 8% (95% CI: 3.2–15.6%) in MAC group and 10% (95%CI: 4.4–18.4%) in RIC/NMA group
• Chronic GVHD (all grades): 19.6% in MAC group (95% CI: 11.3–29.7%) and 14.3% in RIC/NMA group (95% CI: 7.3–23.6%)

Patients in both conditioning groups experienced high rates of bacterial and viral infections, likely due to prolonged myelosuppression and diminished T-cell mediated antiviral immunity related to high doses of PTCy. Infection rates were consistent with prior observations in patients receiving PTCy for GVHD prophylaxis. The ongoing phase II OPTIMIZE trial is investigating the impact of a reduced PTCy dose on infection risk, toxicity, GVHD and OS.

ACCESS trial results show that using PTCy for GVHD prophylaxis in MMUD HCT with PBSC grafts supports strong HCT outcomes for patients without a fully matched donor. Notably, since most enrolled participants belonged to a racial or ethnic group typically underrepresented in HCT clinical trials, these findings represent a major step in helping every eligible patient access this potentially curative therapy with good outcomes.

Al Malki, et al., published in Journal of Clinical Oncology