title: Sequential intensified conditioning and tapering of prophylactic immunosuppressants for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for refractory leukemia.
abstract: For patients with advanced leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), a major obstacle to success, especially in those with a high leukemia cell burden, is relapse of the underlying disease. To improve the outcome of allo-HSCT for refractory leukemia, we investigated the strategy of sequential intensified conditioning and early rapid tapering of prophylactic immunosuppressants therapy for graft-versus-host disease (GVHD) during the early stage after transplantation. A total of 51 patients with refractory leukemia (median age, 30.0 years; unfavorable karyotypes, 49%) received fludarabine (Flu) 30 mg/m(2)/day and cytarabine 2 g/m(2)/day (on days -10 to -6), 4.5 Gy total body irradiation (TBI)/day (on days -5 and -4), and cyclophosphamide (Cy) 60 mg/kg/day and etoposide 600 mg/day (on days -3 and -2) for conditioning. Cyclosporine A (CsA) was withdrawn rapidly in a stepwise fashion to avoid overwhelming GVHD reactions if acute GVHD (aGVHD) did not develop at day +30. All 51 patients developed regimen-related toxicities (13 with grade III-IV); 93.9% of them achieved complete remission by day +30. Median follow-up was 41 months (range, 6.6 to 92.2 months); 5-year overall survival (OS) and disease-free survival (DFS) were 44.6% +/- 8.1% and 38.2% +/- 7.7%, respectively. Thirteen patients relapsed; the 3-year cumulative incidence of leukemia relapse was 33.3%. On multivariate analysis, cytogenetic status was the only significant pretransplantation factor. Survival was better in patients with grade I or II aGVHD than in those without aGVHD. Our data indicate that the sequential strategy of cytoreductive chemotherapy followed immediately by intensified myeloablative (MA) conditioning for allo-HSCT and rapid tapering of prophylactic immunosuppressants for GVHD in the early stage after transplantation has an acceptable toxicity profile and may be a better approach to treating refractory leukemia.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. liuqifa@fimmu.com
authors.forename: Qi-Fa
authors.initials: QF
authors.lastname: Liu
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Fan
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zu-Jun
authors.initials: ZJ
authors.lastname: Jiang
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.forename: Huo
authors.initials: H
authors.lastname: Tan
mesh_terms: D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007938:Leukemia / Q000188:drug therapy / Q000401:mortality / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D011292:Premedication; D011446:Prospective Studies; D012189:Retrospective Studies; D016879:Salvage Therapy; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D000911:Antibodies, Monoclonal; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D019653:Myeloablative Agonists