title: Successful allogeneic hematopoietic stem cell transplantation using triple agent immunosuppression in severe aplastic anemia patients.
abstract: Graft rejection in patients with severe aplastic anemia (SAA) following allogeneic hematopoietic stem cell transplantation (HSCT) is strongly associated with a large number of prior transfusions and with prolonged disease duration before transplant. We retrospectively analyzed the outcomes and the factor affecting these multitransfused SAA patients, who had received triple agent immunosuppression and high doses of stem cells to overcome rejection. In total, 113 patients with SAA who had a median 16 months (range 1-216) of disease duration were transplanted using HLA-matched sibling donors after conditioning with cyclophosphamide (CY), procarbazine (PCB), and ATG. Graft failure occurred in 16 of the eligible 113 patients, and with a median follow-up of 30 months (range, 1-80), probability of overall rejection was 15%. Specifically, the multitransfused patients who received high doses of stem cells with T-cell depletion showed the lowest rejection rate, 5.6%, compared with 30.3% in multitransfused patients with bone marrow stem cells alone (P=0.0310). Disease duration (P=0.0338) and the number of infused CD34+cells (P=0.0101) were associated with a high risk of graft rejection on multivariate analysis. ABO mismatch and the number of CD34+ cells were significant factors in the incidence of acute graft-versus-host-disease (GVHD). The incidence of chronic GVHD among patients with sustained engraftment was 13/109 (11.9%). With the same follow-up period, probability of disease-free survival for the entire group of patients at 6 years was 89% and the only factor associated with long-term survival was rejection (P=0.0241). These results suggest that allogeneic HSCT conditioned with triple agent immunosuppression, and specifically with high-dose stem cell return is probably an effective treatment for successful engraftment in SAA patients with a high risk of rejection.
authors.affiliation: Catholic Hemopoeitic Stem Cell Transplantation Center, The Catholic University of Korea, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: C Y
authors.initials: CY
authors.lastname: Park
authors.forename: Y H
authors.initials: YH
authors.lastname: Park
authors.forename: Y J
authors.initials: YJ
authors.lastname: Kim
authors.forename: D W
authors.initials: DW
authors.lastname: Kim
authors.forename: W S
authors.initials: WS
authors.lastname: Min
authors.forename: C C
authors.initials: CC
authors.lastname: Kim
mesh_terms: D000017:ABO Blood-Group System; D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001803:Blood Transfusion; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006086:Graft vs Host Disease / Q000453:epidemiology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011336:Probability; D012189:Retrospective Studies; D035781:Siblings; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000017:ABO Blood-Group System; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide