title: Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission.
abstract: For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT. Am. J. Hematol. 91:322-329, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Medical Oncology and Haematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Seftel
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachutsetts.
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR®), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.|Medical College of Wisconsin, Division of Biostatistics, Institute for Health and Society, Milwaukee, Wisconsin.
authors.forename: Mei-Jie
authors.initials: MJ
authors.lastname: Zhang
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR®), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Karen Kuhn
authors.initials: KK
authors.lastname: Ballen
authors.affiliation: Department of Hematology, Hôpital Maisonneuve-Rosemont, Montréal, Quebec, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Bergeron
authors.affiliation: Division of Haematology, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Couban
authors.affiliation: South Texas Veterans Health Care System and University of Texas Health Science Center San Antonio, San Antonio, Texas.
authors.forename: César O
authors.initials: CO
authors.lastname: Freytes
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR®), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.affiliation: Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: Department of Medical Oncology and Haematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Kristjan
authors.initials: K
authors.lastname: Paulson
authors.affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR®), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Wael
authors.initials: W
authors.lastname: Saber
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Sallan
authors.affiliation: Department of Medical Oncology/Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Soiffer
authors.affiliation: Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.affiliation: Department of Pediatric Hematopoietic Cell Transplant, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Woolfrey
authors.affiliation: Department of Medical Oncology/Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
authors.affiliation: Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012074:Remission Induction / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult