title: Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.
abstract: In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.
authors.affiliation: Department of Medicine, Capital District Health Authority and Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: stephen.couban@nshealth.ca.
authors.forename: Stephen
authors.initials: S
authors.lastname: Couban
authors.affiliation: Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.affiliation: Hematology-Oncology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lachance
authors.affiliation: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Irwin
authors.initials: I
authors.lastname: Walker
authors.affiliation: Department of Medicine, Leukemia/Bone Marrow Transplant Program, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Toze
authors.affiliation: Department of Medical Oncology and Hematology, CancerCare Manitoba and University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Morel
authors.initials: M
authors.lastname: Rubinger
authors.affiliation: Departments of Oncology and Biostatistics, Princess Margaret Cancer Center and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lipton
authors.affiliation: Department of Medical Oncology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Clinical Haematology and BMT Service, Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Jeff
authors.initials: J
authors.lastname: Szer
authors.affiliation: Hematology Department, Auckland City and Starship Children's Hospitals, Auckland, New Zealand.
authors.forename: Richard
authors.initials: R
authors.lastname: Doocey
authors.affiliation: Department of Hematology, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Lewis
authors.affiliation: Department of Medicine, Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Lothar
authors.initials: L
authors.lastname: Huebsch
authors.affiliation: Department of Medicine, London Health Sciences Center and University of Western Ontario, London, Ontario, Canada.
authors.forename: Kang
authors.initials: K
authors.lastname: Howson-Jan
authors.affiliation: Department of Oncology, Hôpital Hotel-Dieu, Quebec City, Quebec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Lalancette
authors.affiliation: Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Fahad
authors.initials: F
authors.lastname: Almohareb
authors.affiliation: Department of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Chaudhri
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ivison
authors.affiliation: Department of Medicine, Leukemia/Bone Marrow Transplant Program, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Raewyn
authors.initials: R
authors.lastname: Broady
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Megan
authors.initials: M
authors.lastname: Levings
authors.affiliation: Department of Medicine, University of Colorado, Denver, Colorado.
authors.forename: Diane
authors.initials: D
authors.lastname: Fairclough
authors.affiliation: Departments of Oncology and Biostatistics, Princess Margaret Cancer Center and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gerald
authors.initials: G
authors.lastname: Devins
authors.affiliation: Department of Medical Oncology and Hematology, CancerCare Manitoba and University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Szwajcer
authors.affiliation: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Ronan
authors.initials: R
authors.lastname: Foley
authors.affiliation: Department of Medicine, University of Colorado, Denver, Colorado.
authors.forename: Clayton
authors.initials: C
authors.lastname: Smith
authors.affiliation: Departments of Oncology and Biostatistics, Princess Margaret Cancer Center and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tony
authors.initials: T
authors.lastname: Panzarella
authors.affiliation: Department of Medicine, Leukemia/Bone Marrow Transplant Program, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Holly
authors.initials: H
authors.lastname: Kerr
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Amina
authors.initials: A
authors.lastname: Kariminia
authors.affiliation: Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Schultz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000187:drug effects*; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D000069585:Filgrastim / Q000494:pharmacology*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D035781:Siblings; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists; D000069585:Filgrastim
keywords: Blood and marrow transplantation; Donor source; Filgrastim; Graft-versus-host disease; Hematopoietic cell transplantation; Mobilized bone marrow