title: Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) bone marrow transplantation using only pharmacological GVHD prophylaxis.
abstract: OBJECTIVE
  The incidence of severe graft-vs-host disease (GVHD) in unmanipulated human leukocyte antigen (HLA) 2-3 antigen-mismatched bone marrow transplantation (BMT) using cyclosporine and methotrexate as GVHD prophylaxis is 80% to 90%. We investigated whether pharmacological GVHD prophylaxis consisting of four drugs, including a steroid, effectively suppressed GVHD in this transplantation setting.
  
  
  METHODS
  Thirty patients who had hematologic malignancies at an advanced stage or with poor prognosis underwent allogeneic BMT using a myeloablative preconditioning regimen consisting of cyclophosphamide (60 mg/kg x 2), total body irradiation (8-10 Gy), and fludarabine (30 mg/m(2) x 4) with or without cytosine arabinoside (2 g/m(2) x 4), and GVHD prophylaxis consisting of a combination of tacrolimus, methotrexate, mycophenolate mofetil, and methylprednisone (2 mg/kg). Early therapeutic intervention for GVH reaction or grade I GVHD was performed, and steroid was slowly tapered.
  
  
  RESULTS
  All patients achieved donor-type engraftment. Neutrophil (>0.5 x 10(9)/L) and platelet (>20 x 10(9)/L) engraftment was achieved on day 13 and on day 30, respectively. Seventeen patients (56.7%) had no GVHD. Eleven patients (36.7%) developed grade II-III acute GVHD. Seven patients (23.3%) died of transplant-related toxicity, including fungal or viral infections and thrombotic microangiopathy, and four patients died of disease progression. Estimated relapse rate at 3 years was only 20.9%. The probability of survival at 3 years was 49.9%.
  
  
  CONCLUSIONS
  These data suggest that, in unmanipulated HLA-haploidentical allogeneic BMT, this GVHD prophylactic regimen, which includes methylprednisolone 2 mg/kg, and early therapeutic intervention for GVH reaction suppress the incidence of severe GVHD to an acceptable level, while preserving the graft-vs-leukemia effect.
authors.affiliation: Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan. ogawah@hyo-med.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikegame
authors.forename: Katsuji
authors.initials: K
authors.lastname: Kaida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujioka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Hiroya
authors.initials: H
authors.lastname: Tamaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hasei
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iiboshi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tazuke
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Eui Ho
authors.initials: EH
authors.lastname: Kim
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Soma
authors.forename: Takehiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000706:statistics & numerical data; D002648:Child; D003586:Cytomegalovirus Infections / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000601:surgery; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D019520:Living Donors; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000008:administration & dosage; D011183:Postoperative Complications / Q000401:mortality; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods; D014916:Whole-Body Irradiation
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008775:Methylprednisolone; D008727:Methotrexate