title: Multicenter phase II study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG).
abstract: BACKGROUND
  Improvement of current GVHD prophylactic therapies remains an important goal in the allo-HSCT. We have described a novel prophylaxis regimen in a single institution trial. The Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) initiated a phase II multicenter study.
  
  
  METHODS
  The study was designed as a prospective, single arm phase II open-label, multicenter clinical trial. The primary endpoint was improvement of aGVHD by 25% over historical control (40%) in Chinese patients. 508 patients were enrolled. All of the patients received cyclosporine A (CsA), methotrexate (MTX) and mycophenolate mofetil (MMF) (0.5-1.0 g daily for 30 days) as GVHD prophylaxis regimen.
  
  
  RESULTS
  The primary endpoint was met with cumulative incidences of grades 2 to 4 and grades 3 to 4 aGVHD of 23.2% and 10.3%, respectively. Incidence for cGVHD was 67.4%. The non-relapse mortality (NRM) rate was 18.4% at 2 years. The probabilities of leukemia free survival (LFS) for non-advanced stage and advanced stage patients at 2 years were 69.7% and 44.8% respectively (p = 0.000). Recipient age ≥ 40 years, advanced stage and Busulfan-Fludarabine(BuFlu) conditioning regimen were identified as major risk factors for aGVHD. Recipient age ≥ 40 years, BuFlu conditioning regimens, female donor/male recipient and prior aGVHD were associated with cGVHD. Despite lower RM (relapse mortality), patients with grade 2-4 aGVHD had higher NRM and worse OS and LFS compared to patients with grade 0-1 aGVHD. In contrast, patients with cGVHD had better OS and LFS and lower RM compared to patients without cGVHD.
  
  
  CONCLUSIONS
  The novel GVHD regimen decreased the risk for aGVHD by 42% without improving the risk for cGVHD compared to historical controls. Development of aGVHD was associated with worse OS and LFS as well as higher NRM. In contrast, cGVHD was associated with improved OS and LFS likely attributed to a GVL effect.
authors.forename: Yong-Rong
authors.initials: YR
authors.lastname: Lai
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Chen
authors.forename: Deng-Ming
authors.initials: DM
authors.lastname: Hu
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.forename: Qi-Fa
authors.initials: QF
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.forename: Paul
authors.initials: P
authors.lastname: Schwarzenberger
authors.forename: Qiao-Chuan
authors.initials: QC
authors.lastname: Li
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Zhang
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China. xjhrm@medmail.com.cn.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D016572:Cyclosporine / Q000008:administration & dosage*; D004338:Drug Combinations; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007938:Leukemia / Q000401:mortality / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000379:methods; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D008727:Methotrexate