Advances in Stem Cell Transplantation: Improving Outcomes with Less-Than-Perfect Matches

Stephanie Lee, MD, MPH, professor and associate director, Clinical Research Division, Fred Hutch Cancer Center, discusses a study published in the Journal of Clinical Oncology assessing how to improve outcomes for patients undergoing bone marrow transplantation.

Watch the first part of the interview with Dr Lee here.

Watch the second part of the interview with Dr Lee here.

Historically, the established standard for successful hematopoietic stem cell transplantation (HSCT) relied heavily on securing a donor with the closest possible human leukocyte antigen (HLA) match to the patient. For decades, the priority was to identify a matched sibling donor or, failing that, a matched unrelated donor. This traditional approach was rooted in the understanding that a high-fidelity match was critical to minimizing the risk of complications, such as graft-vs-Host disease (GVHD), and maximizing the chance of a successful engraftment. Based on the transplant technology available at the time, these fully matched donors consistently yielded the best outcomes for patients requiring this life-saving procedure. The necessity of a good match was a fundamental, unwavering tenet in the field of transplantation medicine.

However, the landscape of HSCT has undergone a significant transformation thanks to persistent and innovative research. Extensive work has focused on two key areas: exploring the viability of alternative donor sources and developing novel transplant conditioning regimens and protocols designed to mitigate the risks associated with HLA mismatching. This ongoing research has led to profound advancements, most notably improving the safety and efficacy of using donors who were previously considered suboptimal.

Specifically, major strides have been made with mismatched unrelated donors (MMUDs) and haploidentical (or half-matched) family member donors. For MMUDs, advances in immunosuppressive therapies and GvHD prophylaxis have made it safer to proceed with a transplant despite a degree of HLA disparity. Similarly, for haploidentical transplants—which offer a readily available donor for nearly every patient—the development and refinement of techniques, such as posttransplant cyclophosphamide (PTCy), have dramatically improved patient outcomes, reducing severe GVHD and enhancing engraftment rates.

The successful implementation of these new approaches means that the outcomes for transplant recipients receiving cells from MMUDs and half-matched family members are now significantly improved, often approaching those achieved with fully matched donors. As a result, transplant centers are now able to rapidly pivot to these alternative donors without sacrificing a substantial degree of transplant success. This operational shift, built upon years of rigorous clinical investigation, has broadened the donor pool and fundamentally shortened the time it takes to find a viable option, ultimately making the curative potential of stem cell transplantation accessible to a far greater number of patients who previously lacked a suitably matched donor. This collective body of work is a testament to the overall progress in optimizing transplantation, providing critical new pathways for successful treatment.