title: Successful engraftment with fludarabine, cyclophosphamide, and thymoglobulin conditioning regimen in unrelated transplantation for severe aplastic anemia: A phase II prospective multicenter study.
abstract: Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective for preventing graft-versus-host disease (GVHD) and the rejection of organ transplants. After the promising results of our preliminary study, we conducted a phase II prospective multicenter clinical trial using a fludarabine (Flu), cyclophosphamide (Cy), and thymoglobulin conditioning regimen to allow good engraftment in patients who underwent unrelated transplantation for SAA. Twenty-eight patients underwent bone marrow (N = 15) or mobilized peripheral blood (N = 13) transplantation from HLA-matched unrelated donors with Cy (50 mg/kg once daily intravenously (i.v.) on days -9, -8, -7, and -6), Flu (30 mg/m² once daily i.v. on days -5, -4, -3, and -2), and thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2, and -1). Donor-type hematologic recovery was achieved in all patients. The estimated survival rate (SR) was 67.9%, and all the events were treatment-related mortality (TRM), which included thrombotic microangiopathy (N = 2), pneumonia (N = 1), myocardiac infarction (N = 1), posttransplantation lymphoprolifarative disease (N = 3), and chronic GVHD-associated complications (N = 2). The SR of patients who received bone marrow (60.0%) was not different from that of patients who received mobilized peripheral blood (76.9%) (P = .351), but the SR of patients who received more than 15 units of red blood cells before transplantation (45.5%) was significantly lower than that of the other patients (82.4%) (P = .048). The Flu, Cy, and thymoglobulin conditioning regimen achieved promising results for successful engraftment, but the TRM was high. This study was registered at www.clinicaltrials.gov (NCT00737685), and now we are performing a new multicenter study (NCT00882323) to decrease the TRM by reducing the dose of Cy.
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, South Korea.
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.forename: Jun Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Nak Gyun
authors.initials: NG
authors.lastname: Chung
authors.forename: Bin
authors.initials: B
authors.lastname: Cho
authors.forename: Hack Ki
authors.initials: HK
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Young Tak
authors.initials: YT
authors.lastname: Lim
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Sung
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
authors.forename: Ho Joon
authors.initials: HJ
authors.lastname: Im
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Seo
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Hyo Seop
authors.initials: HS
authors.lastname: Ahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000961:Antilymphocyte Serum; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000401:mortality; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000453:epidemiology; D017707:Erythrocyte Transfusion; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007223:Infant; D007958:Leukocyte Count; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000627:therapeutic use; D009504:Neutrophils / Q000166:cytology; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; C512542:thymoglobulin; D014740:Vidarabine; C024352:fludarabine