title: Single-Agent High-Dose Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Human Leukocyte Antigen-Matched Reduced-Intensity Peripheral Blood Stem Cell Transplantation Results in an Unacceptably High Rate of Severe Acute Graft-versus-Host Disease.
abstract: High-dose cyclophosphamide given early after allogeneic hemopoietic cell transplantation has been shown to be effective prophylaxis against graft-versus-host disease (GVHD) in the setting of HLA-matched myeloablative bone marrow grafts, allowing avoidance of long-term immunosuppression with calcineurin inhibitors in some patients. Whether this approach is feasible using granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell grafts is unknown. We conducted an exploratory phase 2 trial of cyclophosphamide given at 50 mg/kg i.v. on days 3 and 4 after transplantation as sole GVHD prophylaxis in recipients of G-CSF-mobilized peripheral blood stem cell grafts from HLA-matched related or unrelated donors after reduced-intensity conditioning therapy with fludarabine, carmustine, and melphalan. Five patients, ages 52 to 67 years, with high-risk hematologic malignancies were enrolled. Four of the 5 developed severe acute GVHD of grades 3 to 4, requiring treatment with methylprednisolone and cyclosporine; 3 were steroid refractory and were given salvage therapy. One of these 4 patients died of hepatic GVHD, one died of sepsis, and 2 survived. We conclude that post-transplantation cyclophosphamide is inadequate as sole GVHD prophylaxis in the context of peripheral blood reduced-intensity conditioning transplantations from HLA-matched donors. This trial is registered at ACTRN12613001154796.
authors: BMT Service, Westmead Hospital, Sydney, New South Wales, Australia. Electronic address: ken.bradstock@sydney.edu.au.
authors: Kenneth F
authors: KF
authors: Bradstock
authors: BMT Service, Westmead Hospital, Sydney, New South Wales, Australia.
authors: Ian
authors: I
authors: Bilmon
authors: BMT Service, Westmead Hospital, Sydney, New South Wales, Australia.
authors: John
authors: J
authors: Kwan
authors: BMT Service, Westmead Hospital, Sydney, New South Wales, Australia.
authors: Kenneth
authors: K
authors: Micklethwaite
authors: BMT Service, Westmead Hospital, Sydney, New South Wales, Australia.
authors: Emily
authors: E
authors: Blyth
authors: BMT Service, Westmead Hospital, Sydney, New South Wales, Australia.
authors: Stephanie
authors: S
authors: Deren
authors: BMT Service, Westmead Hospital, Sydney, New South Wales, Australia.
authors: Angela
authors: A
authors: Bayley
authors: NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
authors: Val
authors: V
authors: Gebski
authors: BMT Service, Westmead Hospital, Sydney, New South Wales, Australia.
authors: David
authors: D
authors: Gottlieb
mesh_terms: D000208:Acute Disease; D000368:Aged; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality*; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D012720:Severity of Illness Index; D019172:Transplantation Conditioning
chemical_list: D006680:HLA Antigens; D003520:Cyclophosphamide
keywords: Allogeneic; Bone marrow transplantation; Cyclophosphamide; Graft-versus-host disease; Peripheral blood stem cells; Prophylaxis