title: A randomized comparison of cyclophosphamide vs. reduced dose cyclophosphamide plus fludarabine for allogeneic hematopoietic cell transplantation in patients with aplastic anemia and hypoplastic myelodysplastic syndrome.
abstract: Recently, a less toxic regimen comprising reduced cyclophosphamide (Cy), fludarabine, and anti-thymocyte globulin (ATG) (Cy-Flu-ATG) was used to condition high-risk patients scheduled for allogeneic hematopoietic cell transplantation (alloHSCT) instead of standard Cy-ATG in patients with severe aplastic anemia (AA). We performed a randomized phase III study to compare the regimen-related toxicities (RRTs) of two different conditioning regimens: Cy-ATG vs. Cy-Flu-ATG. Patients in the Cy-ATG arm received Cy at 200 mg/kg. Those in the Cy-Flu-ATG arm received fludarabine (Flu) at 150 mg/m(2) and Cy at 100 mg/kg. A total of 83 patients (40 in the Cy-ATG and 43 in the Cy-Flu-ATG) were enrolled. Seventy-nine patients had AA and four had MDS. All predefined RRTs were significantly lower in patients of the Cy-Flu-ATG arm (23.3 vs. 55.0 %; p = 0.003). Infection with identified causative organism and sinusoidal obstruction syndrome, hematuria, febrile episodes, and death from any cause tended to be more frequent in Cy-ATG arm but did not differ significantly between arms. There was no difference in neutrophil engraftment failure (2.5 vs. 2.33 %; p = 0.959), acute graft-versus-host disease (GvHD) (15.0 vs. 23.3 %; p = 0.388), and chronic GvHD (16.7 vs. 16.2 %; p = 0.961) between Cy-ATG and Cy-Flu-ATG arms. The 4-year survival rate did not differ between the Cy-ATG and Cy-Flu-ATG arms. Preconditioning with Cy-Flu-ATG was superior to that afforded by Cy-ATG in terms of reducing RRT levels without increasing engraftment failure.
authors.affiliation: Division of Hematology-Oncology, Ulsan University Hospital University of Ulsan College of Medicine, Ulsan, Republic of Korea.
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Joo
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Bae
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Hyun
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Hun Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Jae-Hoo
authors.initials: JH
authors.lastname: Park
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000601:surgery; D019072:Antibiotic Prophylaxis; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage* / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000601:surgery; D011183:Postoperative Complications / Q000453:epidemiology; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine