High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease

• Published in: Blood Vol. 115; no. 16; pp. 3224 - 3230
• Main Authors: Luznik, Leo, Bolaños-Meade, Javier, Zahurak, Marianna, Chen, Allen R., Smith, B. Douglas, Brodsky, Robert, Huff, Carol Ann, Borrello, Ivan, Matsui, William, Powell, Jonathan D., Kasamon, Yvette, Goodman, Steven N., Hess, Allan, Levitsky, Hyam I., Ambinder, Richard F., Jones, Richard J., Fuchs, Ephraim J.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 22.04.2010; Americain Society of Hematology; American Society of Hematology
• Series: Clinical Trials and Observations
• Subjects: Adult; Aged; Biological and medical sciences; Bone Marrow Transplantation - adverse effects; Bone Marrow Transplantation - mortality; Clinical Trials and Observations; Cyclophosphamide - administration & dosage; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Graft vs Host Disease - prevention & control; Hematologic and hematopoietic diseases; Hematologic Neoplasms - mortality; Hematologic Neoplasms - therapy; Humans; Immunosuppressive Agents - administration & dosage; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Transplantation Conditioning - methods; Transplantation, Homologous; Treatment Outcome; Young Adult; Antineoplastic agent; Immunopathology; Graft versus host disease; Hematology; Stem cell; Single dose; Hematopoietic cell; Homograft; Prevention; Alkylating agent; Oxazaphosphinane derivatives; Cyclophosphamide; Nitrogen mustard; Graft; High dose
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-11-251595

Because of its potent immunosuppressive yet stem cell–sparing activity, high-dose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)–matched related donors and 39 had HLA-matched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell–replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission. With a median follow-up of 26.3 months among surviving patients, the cumulative incidence of chronic GVHD is 10%. These results suggest that high-dose posttransplantation cyclophosphamide is an effective single-agent prophylaxis of acute and chronic GVHD after BuCy conditioning and HLA-matched BMT (clinicaltrials.gov no. NCT00134017).