Expanding Donor Access for ASCT in AML: Karilyn Larkin, MD

Allogeneic stem cell transplant remains a critical tool for patients with acute myeloid leukemia (AML) because remission alone rarely eliminates the disease. Chemo-resistant leukemic stem cells can survive initial treatment and cause relapse months or even years later, according to Karilyn Larkin, MD, a hematologic oncologist specializing in AML at The Ohio State University Comprehensive Cancer Center–The James.

The goal of transplant is to replace a patient’s blood and immune system with a donor’s, giving rise to new immune cells capable of hunting down and destroying those resistant leukemic cells—a process known as the graft-vs-leukemia effect.

“The power of an allo transplant is in the fact that you’re giving this whole new immune system and that immune system can seek those guys out and actually kill them off,” Larkin explained.

Historically, the safest option was a fully matched sibling donor, but “if you have any sibling, you’ve got only a 25% chance that that’s going to be a full match,” Larkin said, and global donor registries are heavily skewed toward Eastern European ancestry, creating longstanding inequities in access to transplant. The development of haploidentical (half-matched) transplant, made safer through posttransplant cyclophosphamide (Cytoxan) to deplete newly activated, mismatched immune cells, allowed many more patients to receive a related half-matched transplant. However, this did not help patients without willing or available family donors.

The ACCESS trial (NCT04904588) built on that success by testing whether unrelated donors could be used safely, using peripheral blood–collected stem cells rather than bone marrow. As Larkin noted, prior to this approach, clinicians would have to simply tell the patient there were no donor options. The trial enrolled 3 strata—1 pediatric using bone marrow and 2 adult strata using either fully ablative or reduced-intensity conditioning—excluding patients with myelofibrosis due to engraftment challenges. Investigators tracked graft-vs-host disease (GVHD)–free and relapse-free survival at 1 year, along with rates of acute and chronic GVHD and overall survival.

Larkin emphasized that the underlying goal has always been consistent: “Once we go to that step, everybody really should have a donor.” The findings represent an effort to close longstanding gaps in transplant access.