title: [Sequential intensified conditioning followed by graft-versus-leukemia induction could prevent relapse of refractory acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].
abstract: OBJECTIVE
  To explore the therapeutic effects of sequential intensified conditioning regimen followed by graft-versus-1eukemia (GVL) induction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory advanced acute myeloid leukemia (AML).
  
  
  METHODS
  A total of 72 patients with refractory AML undergoing allo-HSCT from May 2001 to June 2013 were enrolled in this prospective study. Intensified conditioning included fludarabine + cytarabine plus total body irradiation + cyclophosphamide + etoposide. Cyclosporine A was withdrawn rapidly in a stepwise fashion if patients who did not experience acute graft-versus-host disease (aGVHD) at Day + 30 post-transplantation. Donor lymphocytes were infused in patients without grade II or more than grade II aGVHD at Day + 60 post-transplantation.
  
  
  RESULTS
  The median follow-up time was 655 (1-4 200) d post-transplantation. Except for one died of infection and one died of regimen-related toxicity (RRT), the other 70 patients achieved complete remission at the time of neutrophil reconstitution. The mortality of RRT was 1.4% (1/72). The 1-year cumulative incidence of aGVHD and 2-year incidence of chronic GVHD (cGVHD) post-transplantation were 60.7% ± 5.0% and 58.5% ± 4.7%. The 5-year cumulative incidence of relapse post-transplantation was 29.6% ± 6.6%. The 5-year non-relapse mortality was 28.8% ± 6.0%. The 5-year overall and disease-free survival were 51.0% ± 6.5% and 49.9% ± 6.4%. Multivariate analysis revealed that donor lymphocyte infusion, cGVHD and bone marrow blasts at Day 0 were independent prognostic factors for relapse (HR (95% CI): 0.042 (0.007-0.688), 0.009 (0.003-0.345), 3.385 (1.451-7.899)) and survival (HR (95% CI): 0.315 (0.146-0.621), 0.416 (0.200-0.866), 1.332 (1.158-1.533)).
  
  
  CONCLUSIONS
  The strategy of sequential intensified conditioning followed by GVL induction has an acceptable toxicity profile, and could decrease the relapse rate and improve the survival for refractory AML.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xuan
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Fan
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fen
authors.initials: F
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Li
authors.forename: Danian
authors.initials: D
authors.lastname: Nie
authors.forename: Dongjun
authors.initials: D
authors.lastname: Lin
authors.forename: Qianli
authors.initials: Q
authors.lastname: Jiang
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Email: liuqifa628@163.com.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Liu
mesh_terms: D003520:Cyclophosphamide; D003561:Cytarabine; D018572:Disease-Free Survival; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D014184:Transplantation, Homologous; D019737:Transplants; D014916:Whole-Body Irradiation
chemical_list: D003561:Cytarabine; D003520:Cyclophosphamide