Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) bone marrow transplantation using only pharmacological GVHD prophylaxis.
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.
Ogawa
Hiroyasu
H
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan. ogawah@hyo-med.ac.jp
Ikegame
Kazuhiro
K
Kaida
Katsuji
K
Yoshihara
Satoshi
S
Fujioka
Tatsuya
T
Taniguchi
Yuki
Y
Tamaki
Hiroya
H
Inoue
Takayuki
T
Hasei
Hitomi
H
Iiboshi
Yasuhiko
Y
Tazuke
Yuko
Y
Kawakami
Manabu
M
Kim
Eui Ho
EH
Soma
Toshihiro
T
Inoue
Takehiro
T
Kawase
Ichiro
I
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
D006680:HLA Antigens; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008775:Methylprednisolone; D008727:Methotrexate