Tacrolimus as prophylaxis for acute graft-versus-host disease in reduced intensity cord blood transplantation for adult patients with advanced hematologic diseases.
BACKGROUND
Myeloablative cord blood transplantation (CBT) for adult patients offers a 90% chance of engraftment with a 50% rate of transplant-related mortality, mostly attributable to infection. We have demonstrated the feasibility of reduced-intensity CBT (RI-CBT) for adult patients, in which cyclosporine was used for acute graft-versus-host disease (GVHD) prophylaxis. Transplantation-related mortality (TRM) was 27% within 100 days. Therefore our objective was to evaluate the feasibility of RI-CBT with tacrolimus as GVHD prophylaxis for adult patients with hematologic malignancies.


METHODS
Thirty-four patients with a median age of 56.5 years (range; 22-68) with hematologic diseases underwent RI-CBT at Toranomon Hospital between November 2003 and September 2004. Preparative regimen comprised fludarabine 25 mg/m2 on days -7 to -3, melphalan 80 mg/m2 on day -2, and 4 Gy total body irradiation on day -1. GVHD prophylaxis was continuous intravenous infusion of tacrolimus 0.03 mg/kg, starting on day -1.


RESULTS
Thirty-one patients achieved neutrophil engraftment at a median of day 20. Median infused total cell dose was 2.4 x 10E7/kg (range; 1.6-4.8). Thirty-two patients achieved complete donor chimerism at day 60. Grade II-IV acute GVHD occurred in 45% of patients, with a median onset of day 26. Primary disease recurred in five patients, and TRM within 100 days was 12%. Estimated 1-year overall survival was 70%.


CONCLUSIONS
This study demonstrated the possible improvement in transplant-related mortality by tacrolimus as GVHD prophylaxis in adult RI-CBT recipients.
Miyakoshi
Shigesaburo
S
Department of Hematology, Toranomon Hospital, Tokyo, Minato-ku, Japan. s-miyakoshi@dance.ocn.ne.jp
Kami
Masahiro
M
Tanimoto
Tetsuya
T
Yamaguchi
Takuhiro
T
Narimatsu
Hiroto
H
Kusumi
Eiji
E
Matsumura
Tomoko
T
Takagi
Shinsuke
S
Kato
Daisuke
D
Kishi
Yukiko
Y
Murashige
Naoko
N
Yuji
Koichiro
K
Uchida
Naoyuki
N
Masuoka
Kazuhiro
K
Wake
Atsushi
A
Taniguchi
Shuichi
S
D000208:Acute Disease; D000328:Adult; D000368:Aged; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D006402:Hematologic Diseases / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus