克拉屈滨持续静脉滴注组成的CLAG方案治疗难治/复发性急性髓系白血病的临床分析

目的:研究克拉屈滨(2-CdA)持续静脉滴注联合大剂量阿糖胞苷(Ara-C)及粒细胞集落刺激因子(G-CSF)2019年8月在郑州大学附属肿瘤医院血液科等5家医疗单位住院且采用1个疗程CLAG方案(具体为:克拉屈滨5mg/m²,d 1-5,持续24 h静脉滴注;Ara-C 2 g/m²,1/d,d 1-5,静脉滴注;G-CSF 300 mg,1/d,d 0-5,皮下注射)治疗的岁;FAB分型:M₁1例,M₂a 3例,M₂b 4例(其中1例伴髓外侵犯),M₄1例伴髓外侵犯,M₅5例,HAL 1例;NCCN分型:中危组6例,高危组9例;难治8例,复发7例。前期中位化疗次数4(2-8)个(其中例15曾接受化疗8周期,并12例(12/15,80%),CR中位持续时间为65(0-528)d。所有患者化疗后均出现IV级白细胞减少及血小板减少,粒缺期中位持续时间为20(14-33)d,治疗相关死亡1例。7例患者接受异基因造血干细胞移植。15例患者的中位无事件复发/难治性AML,CR高,但CR持续时间短,骨髓抑制重。因此,控制感染是关键,CR后应尽早行异基因造血干细胞移植术。

CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia

Objective:To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine(2-CdA)combined with high-dose cytarabine(Ara-C)and granulocyte colony-stimulating factor(G-CSF)(CLAG regiem)in the treatment of relapsed/refractory acute myeloid leukemia(AML).Methods:Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology,the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively(specifically:cladribine 5 mg/m²,day 1 to day 5,continuous 24-hour intravenous infusion;Ara-C2 g/m²,1 time/day,day 1 to day 5,intravenous infusion;G-CSF 300 mg,1 time/day,day 0 to day 5,subcutaneous injection).Results:Among the 15 patients with refractory/relapsed AML,9 males and 6 females,the median age was 35(13-63)years old.FAB classification:1 case of M₁,3 cases of M₂ a,4 cases of M₂ b(including 1 case with extramedullary invasion),1 case of M₄ with extramedullary invasion,5 cases of M₅,1 case of HAL;NCCN classification:6 cases in intermediate risk group,9 cases in high risk group;8 cases refractory,7 cases relapsed.The median time of pre-chemotherapy was4(2-8)(of which NO.15 had received 8 cycles of chemotherapy and received CLL1-CAR-T),and the median white blood cell count before chemotherapy was 12.27(from 0.78 to 5.29)×10⁹/L.After 1 course of treatment with CLAG regimen,12 patients achieved complete remission(12/15,80%),and the median duration of CR was 65 days(0-528)days.IV grade leukopenia and thrombocytopenia was found in all the patients after chemotherapy.The median duration of granulocytosis was 20(14 to 33)days,and 1 patient died.Seven patients received allogeneic hematopoietic stem cell transplantation.The median EFS and OS time of 15 patients was 85(19-558)days and 117(19-558)days,respectively.Conclusion:The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients,but the duration of CR is short,myelosuppression is sever,so that infection control is the key.Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.