title: Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial.
abstract: B cells are implicated in the pathophysiology of chronic graft-vs-host disease (GVHD), and phase 2 trials suggest that B cell depletion can treat established chronic GVHD. We hypothesized that posttransplantation B cell depletion could prevent the occurrence of chronic GVHD. We performed a 65-patient phase 2 trial of rituximab (375 mg/m(2) IV), administered at 3, 6, 9, and 12 months after transplantation. Rituximab administration was safe without severe infusional adverse events. The cumulative incidences of chronic GVHD and systemic corticosteroid-requiring chronic GVHD at 2 years from transplantation were 48% and 31%, respectively, both lower than the corresponding rates in a concurrent control cohort (60%, P = .1, and 48.5%, P = .015). There was no difference in relapse incidence, but treatment-related mortality at 4 years from transplantation was significantly lower in treated subjects when compared with controls (5% vs 19%, P = .02), and overall survival was superior at 4 years (71% vs 56%, P = .05). At 2 years from transplantation, the B-cell activating factor/B-cell ratio was significantly higher in subjects who developed chronic GVHD in comparison with those without chronic GVHD (P = .039). Rituximab can prevent systemic corticosteroid-requiring chronic GVHD after peripheral blood stem cell transplantation and should be tested in a prospective randomized trial.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. corey_cutler@dfci.harvard.edu
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.forename: Bhavjot
authors.initials: B
authors.lastname: Bindra
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sarantopoulos
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
authors.forename: Jacalyn
authors.initials: J
authors.lastname: Rosenblatt
authors.forename: Sean
authors.initials: S
authors.lastname: McDonough
authors.forename: Phandee
authors.initials: P
authors.lastname: Watanaboonyongcharoen
authors.forename: Philippe
authors.initials: P
authors.lastname: Armand
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.forename: Brett
authors.initials: B
authors.lastname: Glotzbecker
authors.forename: Edwin
authors.initials: E
authors.lastname: Alyea
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D011446:Prospective Studies; D000069283:Rituximab; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D000069283:Rituximab