Combination of tacrolimus, methotrexate, and methylprednisolone prevents acute but not chronic graft-versus-host disease in unrelated bone marrow transplantation.
BACKGROUND
Graft-versus-host disease (GVHD) is still a major problem in allogeneic bone marrow transplantation (BMT). Prophylactic regimens used against GVHD in unrelated BMT, including cyclosporine (CsA)-plus-methotrexate (MTX), CsA-plus-MTX-plus-prednisone, and tacrolimus (FK506)-plus-MTX, are still unsatisfactory (34-70% occurrence of grades II-IV GVHD). To address this problem, we examined the efficacy of FK506-plus-MTX-plus-methylprednisolone (mPSL) in 20 patients who underwent BMT from unrelated donors.


METHODS
All patients received FK506 beginning the day before transplantation at a dose of 0.03 mg/kg per day by continuous intravenous (IV) infusion. MTX was administered at a dose of 10 mg/m(2) IV on day 1, and 7 mg/m(2) on days 3, 6, and 11. Intravenous administration of mPSL was started at a dose of 2 mg/kg per day on day 1. In the absence of acute GVHD, mPSL was gradually tapered from day 29.


RESULTS
Development of acute GVHD was almost completely suppressed (one patient with grade I, none with grades II-IV). However, the incidence and severity of chronic GVHD did not decrease. Eight of 12 patients with extensive chronic GVHD died of thrombotic microangiopathy or infection. A vigorous fluctuation (>100 U/mL per 10 days) of the soluble interleukin 2 receptor level in the serum after engraftment was highly related to the occurrence of chronic GVHD.


CONCLUSIONS
An FK506-plus(+)-MTX-plus(+)-mPSL prophylactic regimen could almost completely suppress acute GVHD but not chronic GVHD in unrelated BMT. In this GVHD prophylactic system, the extent of the change of soluble interleukin 2 receptor level may be a good predictor of development of chronic GVHD.
Ogawa
Hiroyasu
H
Departments of Molecular Medicine, and Clinical Laboratory Science, Osaka University Graduate School of Medicine, Osaka, Japan. ogawah@imed3.med.osaka-u.ac.jp.
Soma
Toshihiro
T
Hosen
Naoki
N
Tatekawa
Toyoshi
T
Tsuboi
Akihiro
A
Oji
Yusuke
Y
Tamaki
Hiroya
H
Kawakami
Manabu
M
Ikegame
Kazuhiro
K
Murakami
Masaki
M
Fujioka
Tatsuya
T
Kim
Eui Ho
EH
Oka
Yoshihiro
Y
Sugiyama
Haruo
H
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000097:blood; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000401:mortality; D002423:Cause of Death; D002908:Chronic Disease; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate; D008775:Methylprednisolone; D016559:Tacrolimus; D014184:Transplantation, Homologous
D000956:Antigens, Viral; D007166:Immunosuppressive Agents; D016559:Tacrolimus; D008775:Methylprednisolone; D008727:Methotrexate