title: [Cohort Study on GHA and New Combined Priming Chemotherapeutic Regimens in Treatment of Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome].
abstract: OBJECTIVE
  To explore the clinical efficacy and adverse effects of GHA(G-CSF+homoharringtonin+cytarabine C) and new combined priming chemotherapeutic regimens(GHAA/GHTA) with high efficacy and low toxicity for treatment of relapsed and refractory acute myeloid leukemia(AML) and myelodysplastic syndrome(MDS), and to analyze the relation of above-mentioned regimens with the expression of co-stimuolating molecule B7.1.
  
  
  METHODS
  Standard GHA regimen consisting of G-CSF: 100 µg/(m2·d) subcutaneous injection, d 0-14; homoharringtonine: 1.0 mg/(m2·d) intravenous drip, d 1-14; Ara-C: 7.5-10 mg/(m2·d) subcutaneous injection, q12h, d 1-14. Other regimens as GHAA/GHTA were combined respectively with aclarubicin 20 mg d 1-7, or pirarubicin 20 mg d 1-7. 74 patients with refractory AML and 46 patients with MDS received these priming chemotherapy. The clinical efficacy and toxicity of above-mentioned priming chemotherapy were compared with 56 patients received routine chemotherapy (MA/TAE) respectively. And the expression of costimulatory molecule B7.1 on leukemia cells in patients of different subtypes was also detected by immunofluoressence and its relationship with clinical efficiency was explored.
  
  
  RESULTS
  (1) for AML patients treated with priming chemotherapy, the total remission was 67.56% (CR 54.05%, PR 13.51%), which was much higher than that of patients received routine chemotherapy (P<0.05). The CR rate of AML-M2 and AML-M5 group (65.51%, 61.90% respectively) was much higher than that of AML other subtypes (P<0.05), and the longest remission period lasted for 4 years; (2) for MDS patients treated with priming chemotherapy, the total remission was 60.87% (CR 45.65%, PR 15.22%), which was also significantly higher than that of patients received routine chemotherapy (P<0.05); (3) in comparison with patients received standard GHA priming regimen, the remission rate of combined priming chemotherapy GHAA/GHTA was significantly higher both in patients with AML (85.18%) and MDS (81.25%); (4) side effects after chemotheropy, including granulocyte deficiency, thrombocytopenia and anemia etc, lasted for 7-14 days; the severe infection rate was 1%, there were no severe bleeding, digest effect and damage of function in heart, liver and kidney. The therapy-related mortality was zero. Compared with routine chemotherapy, priming chemotherapy proved significantly safe and effective (P<0.05); (5) the expression rate of costimulatory molecule B7.1 showed large variance between AML and MDS, it was higher in AML-M2/AML-M5 and lower in AML of other subtypes (P<0.05). In the same case, B7.1 expression was positive correlated with efficiency of priming chemotherapy.
  
  
  CONCLUSIONS
  GHA priming chemotherapy, as well as other combination regimens GHAA/GHTA, are well-tolerated, effective regimens for refractory AML and advanced MDS, without severe side effects and therapy-related mortality. Especially the new regimens GHAA/GHTA has better efficacy, which are proved more efficient than conventional GHA. Efficiency of priming chemotherapy is positive correlated with B7.1 expression, its mechanism will be further explored.
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. E-mail: maxr0910@163.com.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Ma
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Wang-Gang
authors.initials: WG
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Yin-Xia
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Xing-Mei
authors.initials: XM
authors.lastname: Cao
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: He
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Liu-Fang
authors.initials: LF
authors.lastname: Gu
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lei
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Peng-Yu
authors.initials: PY
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Wan-Hong
authors.initials: WH
authors.lastname: Zhao
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Fang-Xia
authors.initials: FX
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
mesh_terms: D015250:Aclarubicin / Q000031:analogs & derivatives; D000971:Antineoplastic Combined Chemotherapy Protocols; D018122:B7-1 Antigen; D015331:Cohort Studies; D003561:Cytarabine; D004317:Doxorubicin / Q000031:analogs & derivatives; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes; D006248:Harringtonines; D000077863:Homoharringtonine; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D009190:Myelodysplastic Syndromes; D012008:Recurrence; D013921:Thrombocytopenia
chemical_list: D018122:B7-1 Antigen; D006248:Harringtonines; C011157:aclacinomycins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D000077863:Homoharringtonine; D015250:Aclarubicin; D004317:Doxorubicin; C027260:pirarubicin