NCI First International Workshop on The Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: report from the committee on prevention of relapse following allogeneic cell transplantation for hematologic malignancies

Abstract

Prevention of relapse after allogeneic hematopoietic stem cell transplantation is the most likely approach to improve survival of patients treated for hematologic malignancies. Herein we review the limits of currently available transplant therapies and the innovative strategies being developed to overcome resistance to therapy or to fill therapeutic modalities not currently available. These novel strategies include nonimmunologic therapies, such as targeted preparative regimens and posttransplant drug therapy, as well as immunologic interventions, including graft engineering, donor lymphocyte infusions, T cell engineering, vaccination, and dendritic cell-based approaches. Several aspects of the biology of the malignant cells as well as the host have been identified that obviate success of even these newer strategies. To maximize the potential for success, we recommend pursuing research to develop additional targeted therapies to be used in the preparative regimen or as maintenance posttransplant, better characterize the T cell and dendritic cells subsets involved in graft-versus-host disease and the graft-versus-leukemia/tumor effect, identify strategies for timing immunologic or nonimmunologic therapies to eliminate the noncycling cancer stem cell, identify more targets for immunotherapies, develop new vaccines that will not be limited by HLA, and develop methods to identify populations at very high risk for relapse to accelerate clinical development and avoid toxicity in patients not at risk for relapse.

Figure 1

Conditioning Regimens for Allogeneic HSCT (figure courtesy of H.J. Deeg).

Figure 2

Estimates of the probability of overall survival and disease-free survival for AML CR1 patients with negative vs. positive MFC results pre-HSCT (R. Walter, et al., in press)

Figure 3

Probability of relapse for advanced AML patients who received ¹³¹I-BC8 Ab combined with CY/TBI. Thick solid line = dose to BM > 7 cGy/mCi; thick dashed line = dose to BM < 7 cGy/mCi.[19]

Figure 4

Estimates of the probability of OS, DFS, TRM, and relapse among patients treated at the MTD of 24 Gy of radiation delivered to the liver by the ¹³¹I-BC8 Ab, followed by TBI/FLU.[19]