title: Tacrolimus instead of cyclosporine used for prophylaxis against graft-versus-host disease improves outcome after hematopoietic stem cell transplantation from unrelated donors, but not from HLA-identical sibling donors: a nationwide survey conducted in Japan.
abstract: Despite recent advances, graft-versus-host disease (GVHD) remains the main cause of treatment failure for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Tacrolimus (FK506) has been increasingly used in place of cyclosporine (CSP), and several studies have shown that FK506 reduces the incidence of acute GVHD more effectively than does CSP. However, no survival benefits have been demonstrated, and no established consensus exists on the choice of these immunosuppressive agents. To compare a CSP-based and an FK506-based regimen, we performed a large-scale retrospective study by using the data of 1935 patients who underwent HSCT from HLA-identical sibling donors (SIB-HSCT) and 777 patients who underwent HSCT from unrelated donors (UD-HSCT). For patients undergoing UD-HSCT, FK506 significantly reduced the risk of acute GVHD and treatment-related mortality (TRM) without an increase in relapse, thus improving overall survival (OS) (hazard ratio (HR): 2.20, 95% confidence interval (CI): 1.60-3.04, P<0.0001 for grade II-IV acute GVHD; HR: 1.81, 95% CI: 1.32-2.48, P=0.0003 for TRM; HR: 1.62, 95% CI: 1.23-2.14, P=0.0007 for OS). This superiority of FK506 was not observed in SIB-HSCT cases. These findings indicate that the use of FK506 instead of CSP for GVHD prophylaxis is beneficial for patients undergoing UD-HSCT.
authors.affiliation: Department of Hematology, Nagoya University Graduate School of Medicine, Nagoya, Japan. myanada@med.nagoya-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Yanada
authors.forename: N
authors.initials: N
authors.lastname: Emi
authors.forename: T
authors.initials: T
authors.lastname: Naoe
authors.forename: H
authors.initials: H
authors.lastname: Sakamaki
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Hirabayashi
authors.forename: A
authors.initials: A
authors.lastname: Hiraoka
authors.forename: Y
authors.initials: Y
authors.lastname: Kanda
authors.forename: R
authors.initials: R
authors.lastname: Tanosaki
authors.forename: S
authors.initials: S
authors.lastname: Okamoto
authors.forename: K
authors.initials: K
authors.lastname: Iwato
authors.forename: Y
authors.initials: Y
authors.lastname: Atsuta
authors.forename: N
authors.initials: N
authors.lastname: Hamajima
authors.forename: M
authors.initials: M
authors.lastname: Tanimoto
authors.forename: S
authors.initials: S
authors.lastname: Kato
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D035781:Siblings; D033581:Stem Cell Transplantation / Q000706:statistics & numerical data; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus