title: Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) stem cell transplantation using nonmyeloablative conditioning.
abstract: The major problems in human leukocyte antigen (HLA)-mismatched stem cell transplantation (SCT) are graft failure and graft-versus-host disease (GVHD). Less-intensive regimens should be associated with a lower release of inflammatory cytokines and possibly less GVHD. The objective of this study was to investigate whether HLA-haploidentical SCT can be performed using nonmyeloablative conditioning and pharmacologic GVHD prophylaxis, including glucocorticoids. Using conditioning consisting of fludarabine, busulfan, and anti-T-lymphocyte globulin and GVHD prophylaxis consisting of tacrolimus and methylprednisolone (1 mg/kg/day), 26 patients who had hematologic malignancies in an advanced stage or with a poor prognosis underwent transplantation using peripheral blood stem cells from an HLA-haploidentical donor (2-3 antigen mismatches in the graft-versus-host [GVH] direction) without T-cell depletion. All patients except for 1 achieved donor-type engraftment. Rapid hematologic engraftment was achieved (neutrophils > 0.5 x 10(9)/L on day 12 and platelets > 20 x 10(9)/L on day 12), with full donor chimerism achieved by day 14. Fifteen patients did not develop acute GVHD clinically, and only 5 patients developed grade II GVHD. The recovery of CD4+ T cells was delayed compared with that of CD8+ T cells. Sixteen of the 26 patients are alive in complete remission. Four died of transplantation-related causes, and 6 died of progressive disease. These data suggest that nonmyeloablative conditioning, GVHD prophylaxis consisting of tacrolimus and methylprednisolone, and early therapeutic intervention for the GVH reaction allow stable engraftment and effectively suppress GVHD in HLA 2-3 antigen-mismatched SCT.
authors.affiliation: Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan. ogawah@hyo-med.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikegame
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujioka
authors.forename: Tomoki
authors.initials: T
authors.lastname: Masuda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hasei
authors.forename: Katsuji
authors.initials: K
authors.lastname: Kaida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Eui Ho
authors.initials: EH
authors.lastname: Kim
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D002066:Busulfan / Q000008:administration & dosage; D018791:CD4 Lymphocyte Count; D003131:Combined Modality Therapy; D016207:Cytokines / Q000502:physiology; D018572:Disease-Free Survival; D005190:Family; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006680:HLA Antigens / Q000032:analysis* / Q000235:genetics; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000601:surgery*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000401:mortality / Q000601:surgery; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality / Q000706:statistics & numerical data*; D012008:Recurrence; D012074:Remission Induction; D013601:T-Lymphocytes; D016559:Tacrolimus / Q000627:therapeutic use; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000401:mortality; D014184:Transplantation, Homologous / Q000276:immunology*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000961:Antilymphocyte Serum; D016207:Cytokines; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D016559:Tacrolimus; D008775:Methylprednisolone