title: Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation.
abstract: The cumulative incidence of National Institutes of Health (NIH)-defined chronic graft-versus-host disease (GVHD) requiring systemic treatment is ∼35% at 1 year after transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized blood cells from HLA-matched related or unrelated donors. We hypothesized that high-dose cyclophosphamide given after G-CSF-mobilized blood cell transplantation would reduce the cumulative 1-year incidence of chronic GVHD to 15% or less. Forty-three patients with high-risk hematologic malignancies (median age, 43 years) were enrolled between December 2011 and September 2013. Twelve (28%) received grafts from related donors, and 31 (72%) received grafts from unrelated donors. Pretransplant conditioning consisted of fludarabine and targeted busulfan (n = 25) or total body irradiation (≥12 Gy; n = 18). Cyclophosphamide was given at 50 mg/kg per day on days 3 and 4 after transplantation, followed by cyclosporine starting on day 5. The cumulative 1-year incidence of NIH-defined chronic GVHD was 16% (95% confidence interval, 5-28%). The cumulative incidence estimates of grades 2-4 and 3-4 acute GVHD were 77% and 0%, respectively. At 2 years, the cumulative incidence estimates of nonrelapse mortality and recurrent malignancy were 14% and 17%, respectively, and overall survival was projected at 70%. Of the 42 patients followed for ≥1 year, 21 (50%) were relapse-free and alive without systemic immunosuppression at 1 year after transplantation. Thus, myeloablative pretransplant conditioning can be safely combined with high-dose cyclophosphamide after transplantation, and the risk of chronic GVHD associated with HLA-matched mobilized blood cell grafts can be substantially reduced. This trial was registered at www.clinicaltrials.gov as #NCT01427881.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine.
authors.forename: Marco
authors.initials: M
authors.lastname: Mielcarek
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Terry
authors.initials: T
authors.lastname: Furlong
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine.
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Donnell
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Biostatistics.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and School of Pharmacy, and.
authors.forename: Jeannine S
authors.initials: JS
authors.lastname: McCune
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine.
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Pediatrics, University of Washington, Seattle, WA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Carpenter
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine.
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002066:Busulfan / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy; D019650:Hematopoietic Stem Cell Mobilization; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000009:adverse effects; D009190:Myelodysplastic Syndromes / Q000628:therapy; D018365:Neoplasm, Residual; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D011446:Prospective Studies; D012306:Risk; D012720:Severity of Illness Index; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine