Outcomes after 7/8 and <7/8 mismatched unrelated donor PBSC transplantation with PTCy: results from the ACCESS trial
Antonio Martin Jimenez Jimenez, Joseph Stanek, Brent R Logan, Erin Leckrone, Heather E. Stefanski, Jeffery J. Auletta, Stephen R. Spellman, Craig Malmberg, Medhat Askar, Rachel N. Cusatis, Brian C. Shaffer, Dipenkumar Modi, Farhad Khimani, Mahasweta Gooptu, Mehdi Hamadani, Martin Maiers, Stephanie Bo-Subait, Javier Bolaños-Meade, Uttam Rao, Jordan Milner, Ramzi Abboud, Katarzyna Joanna Jamieson, George Carrum, Bhagirathbhai Dholaria, William J. Hogan, Ran Reshef, Satyajit Kosuri, Rachel J. Cook, Karen Ballen, Alison W. Loren, Karilyn Larkin, Sally Arai, Muna Qayed, Sung Won Choi, Larisa Broglie, Bronwen E. Shaw, Steven M. Devine, Monzr M. Al MalkiACCESS is a prospective, multicenter phase II trial evaluating peripheral blood stem cell (PBSC) transplantation using 4-7/8 HLA-mismatched unrelated donors (MMUD) with post-transplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate. Adults undergoing first HCT with myeloablative (MAC) or reduced-intensity/nonmyeloablative (RIC/NMA) conditioning were enrolled, with donors aged 18-35 years and matched at 4/8-7/8 HLA loci by high-resolution typing. This expanded analysis includes all enrolled adult PBSC recipients, including the protocol-specified RIC/NMA cohort expansion, to improve precision of outcome estimates and provide descriptive analyses by HLA match level. Among 268 adults, 183 received 7/8 and 85 received <7/8 MMUD grafts; 82.4% of the <7/8 cohort received 6/8 grafts. Median follow-up among survivors was 11.9 months. At 1-year, overall survival was 78.6% (95% CI, 71.9-83.9) in the 7/8 cohort and 85.6% (95% CI, 76.0-91.5) in the <7/8 cohort. One-year relapse, non-relapse mortality, and GVHD-free relapse-free survival were 17.1%, 13.7%, and 51.1% versus 22.8%, 8.4%, and 54.6%, respectively. The cumulative incidence of grade II-IV and grade III-IV acute GVHD by day 100 was 36.6% and 7.7% in the 7/8 cohort versus 28.3% and 5.9% in the <7/8 cohort. Moderate-to-severe chronic GVHD at 1 year was 11.3% versus 7.7%, respectively. Among adult ACCESS recipients treated on a uniform young-donor PBSC/PTCy platform, short-term outcomes with predominantly 6/8 MMUD transplantation were encouraging. Because donor match level was not prospectively assigned and between-group comparisons were exploratory, these findings are descriptive and should not be interpreted as establishing equivalence with 7/8 MMUD transplantation. (Registered as NCT04904588 at CT.gov)