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.
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
Mitchell S
MS
Cairo
Craig T
CT
Jordan
Carlo C
CC
Maley
Clifford
C
Chao
Ari
A
Melnick
Scott A
SA
Armstrong
Warren
W
Shlomchik
Jeff
J
Molldrem
Soldano
S
Ferrone
Crystal
C
Mackall
Laurence
L
Zitvogel
Michael R
MR
Bishop
Sergio A
SA
Giralt
Carl H
CH
June
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