NCI first International Workshop on the biology, prevention, and treatment of relapse after allogeneic hematopoietic stem cell transplantation: report from the committee on the biological considerations of hematological relapse following allogeneic stem cell transplantation unrelated to graft-versus-tumor effects: state of the science.
Hematopoietic malignant relapse still remains the major cause of death following allogeneic hematopoietic stem cell transplantation (HSCT). Although there has been a large focus on the immunologic mechanisms responsible for the graft-versus-tumor (GVT) effect or lack thereof, there has been little attention paid to investigating the biologic basis of hematologic malignant disease relapse following allogeneic HSCT. There are a large number of factors that are responsible for the biologic resistance of hematopoietic tumors following allogeneic HSCT. We have focused on 5 major areas including clonal evolution of cancer drug resistance, cancer radiation resistance, genomic basis of leukemia resistance, cancer epigenetics, and resistant leukemia stem cells. We recommend increased funding to pursue 3 broad areas that will significantly enhance our understanding of the biologic basis of malignant relapse after allogeneic HSCT, including: (1) genomic and epigenetic alterations, (2) cancer stem cell biology, and (3) clonal cancer drug and radiation resistance.
Cairo
Mitchell S
MS
Department of Pediatrics, Medicine, and Pathology, Columbia University, Morgan Stanley Children's Hospital, New York-Presbyterian Hospital, New York, New York 10032, USA. mc1310@columbia.edu
Jordan
Craig T
CT
Maley
Carlo C
CC
Chao
Clifford
C
Melnick
Ari
A
Armstrong
Scott A
SA
Shlomchik
Warren
W
Molldrem
Jeff
J
Ferrone
Soldano
S
Mackall
Crystal
C
Zitvogel
Laurence
L
Bishop
Michael R
MR
Giralt
Sergio A
SA
June
Carl H
CH
D035843:Biomedical Research; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D044127:Epigenesis, Genetic / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D020350:Graft vs Tumor Effect; D019337:Hematologic Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D014411:Neoplastic Stem Cells / Q000502:physiology; D011836:Radiation Tolerance / Q000502:physiology; D055502:Secondary Prevention; D014184:Transplantation, Homologous