PMID- 17920757
OWN - NLM
STAT- MEDLINE
DCOM- 20080304
LR  - 20161124
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 36
IP  - 1
DP  - 2008 Jan
TI  - Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) bone marrow 
      transplantation using only pharmacological GVHD prophylaxis.
PG  - 1-8
AB  - 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. 
      MATERIALS AND 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.
FAU - Ogawa, Hiroyasu
AU  - Ogawa H
AD  - Department of Molecular Medicine, Osaka University Graduate School of Medicine, 
      Suita City, Osaka, Japan. ogawah@hyo-med.ac.jp
FAU - Ikegame, Kazuhiro
AU  - Ikegame K
FAU - Kaida, Katsuji
AU  - Kaida K
FAU - Yoshihara, Satoshi
AU  - Yoshihara S
FAU - Fujioka, Tatsuya
AU  - Fujioka T
FAU - Taniguchi, Yuki
AU  - Taniguchi Y
FAU - Tamaki, Hiroya
AU  - Tamaki H
FAU - Inoue, Takayuki
AU  - Inoue T
FAU - Hasei, Hitomi
AU  - Hasei H
FAU - Iiboshi, Yasuhiko
AU  - Iiboshi Y
FAU - Tazuke, Yuko
AU  - Tazuke Y
FAU - Kawakami, Manabu
AU  - Kawakami M
FAU - Kim, Eui Ho
AU  - Kim EH
FAU - Soma, Toshihiro
AU  - Soma T
FAU - Inoue, Takehiro
AU  - Inoue T
FAU - Kawase, Ichiro
AU  - Kawase I
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
DEP - 20071017
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - 0 (HLA Antigens)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Myeloablative Agonists)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - WM0HAQ4WNM (Tacrolimus)
RN  - X4W7ZR7023 (Methylprednisolone)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Bone Marrow Transplantation/adverse effects/*immunology/statistics & numerical 
      data
MH  - Child
MH  - Cytomegalovirus Infections/epidemiology
MH  - Drug Therapy, Combination
MH  - Female
MH  - Graft vs Host Disease/epidemiology/*prevention & control
MH  - HLA Antigens/genetics/*immunology
MH  - Hematologic Neoplasms/mortality/surgery
MH  - *Histocompatibility
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/*therapeutic use
MH  - Incidence
MH  - Living Donors
MH  - Methotrexate/administration & dosage/*therapeutic use
MH  - Methylprednisolone/administration & dosage/*therapeutic use
MH  - Mycophenolic Acid/administration & dosage/*analogs & derivatives/therapeutic use
MH  - Myeloablative Agonists/administration & dosage
MH  - Postoperative Complications/mortality
MH  - Tacrolimus/administration & dosage/*therapeutic use
MH  - Transplantation Conditioning/methods
MH  - Whole-Body Irradiation
EDAT- 2007/10/09 09:00
MHDA- 2008/03/05 09:00
CRDT- 2007/10/09 09:00
PHST- 2007/05/13 00:00 [received]
PHST- 2007/07/30 00:00 [revised]
PHST- 2007/08/08 00:00 [accepted]
PHST- 2007/10/09 09:00 [pubmed]
PHST- 2008/03/05 09:00 [medline]
PHST- 2007/10/09 09:00 [entrez]
AID - S0301-472X(07)00521-8 [pii]
AID - 10.1016/j.exphem.2007.08.013 [doi]
PST - ppublish
SO  - Exp Hematol. 2008 Jan;36(1):1-8. doi: 10.1016/j.exphem.2007.08.013. Epub 2007 Oct 
      17.