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.
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.
Alyea
Edwin P
EP
Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA. edwin_alyea@dfci.harvard.edu
DeAngelo
Daniel J
DJ
Moldrem
Jeffrey
J
Pagel
John M
JM
Przepiorka
Donna
D
Sadelin
Michel
M
Young
James W
JW
Giralt
Sergio
S
Bishop
Michael
M
Riddell
Stan
S
D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D055502:Secondary Prevention; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous