Posttransplant Relapse

Abstract

Outcomes after autologous and allogeneic hematopoietic stem cell transplant (HSCT) have improved substantially as advances in supportive care and conditioning regimens, such as the introduction of reduced-intensity allogeneic transplants, have dramatically reduced treatment-related morbidity and mortality. Unfortunately, disease relapse remains a major cause of transplant failure and patient mortality. Center for International Blood and Marrow Transplant Research (CIBMTR) data identify relapse as the cause of 78 % of autologous transplant-related deaths, 34 % of related allogeneic transplant deaths, and 23 % of unrelated transplant deaths. Lack of effective and well-tolerated therapeutic options for relapse after transplant is a major barrier in the care of these patients. To optimize outcomes, management of disease relapse after HSCT must be highly individualized and based on both patient and disease features.

Relapse after autologous transplant is managed with further chemotherapy, second autologous transplant, or allogeneic transplant with success of therapy dictated by nature of the underlying malignancy, disease response to current/previous therapy, and other host factors. Targeted and novel agents will play an expanding role in the setting of relapse after autologous transplant, as well as for the prevention of relapse (maintenance, consolidation).

Relapse after allogeneic transplant is addressed principally by manipulations designed to enhance the graft-versus-leukemia (GVL) effect including withdrawal of immunosuppression, donor lymphocyte infusion (DLI), and—very selectively—second allogeneic transplant. These approaches are inadequate in the majority of cases and improved therapies are needed. Progress will involve enhancement of GVL via a variety of approaches (such as manipulated or modified DLI), integration of cellular and noncellular-targeted therapies, and development of strategies to prevent relapse via maintenance programs and the detection of early relapse with earlier intervention. Mechanisms for the rapid development and testing of new approaches are needed.