The Persistent Challenge of Posttransplant Relapse

In an interview with Targeted Oncology, Heather Stefanski, MD, PhD, vice president of the Center for International Blood and Marrow Transplant Research and Clinical Services at NMDP, identifies a critical and lingering unmet need within the field of hematopoietic stem cell transplantation: the effective mitigation of disease relapse. Despite significant advancements in medical technology and procedural safety, Stefanski emphasizes that relapse remains the most common complication facing patients today. Stefanski clarifies that the issue is generally not a result of the transplant procedure failing mechanically; rather, it is a distinct phenomenon that occurs in the posttransplant period, casting a shadow over what is hopefully a curative journey.

According to Stefanski's assessment, there are several root causes of recurrence. She outlines 2 primary scenarios: First, there is the issue of preexisting disease burden; some patients enter the transplant process with a level of disease activity that the transplant cannot fully eradicate. Second, Stefanski points to the biological resilience of the malignancy itself. Using the descriptor that the disease is "too smart," she highlights the cancer's ability to evolve, adapt, and evade the therapeutic effects of the new immune system, eventually resurfacing despite aggressive intervention.

Stefanski reveals a shift in clinical priorities based on historical successes. Stefanski acknowledges the substantial progress the medical community has made in graft-vs-host disease (GVHD). While admitting that there is still work to be done to perfect GVHD management, Stefanski suggests that the battle against toxicity has seen more victories than the battle against disease recurrence. Consequently, the management of GVHD is no longer the singular, insurmountable barrier it once was.

Stefanski posits that the "next frontier" of transplant medicine must be a pivot toward efficacy and sustainability. The focus is moving away from merely surviving the procedure and managing its adverse effects, toward ensuring the longevity of the cure. The ultimate goal, she says, is to discover novel strategies—likely involving maintenance therapies or targeted interventions—that prevent the disease from outsmarting the treatment, thereby securing a relapse-free future for patients.