CLAG方案治疗复发、难治急性髓系白血病疗效、安全性分析及随访
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摘要
目的:观察CLAG方案(克拉屈滨+阿糖胞苷+粒细胞集落刺激因子)治疗难治、复发急性髓系白血病(acute myeloid leukemia,AML)的疗效、安全性和不良反应。方法 :回顾性分析2015年7月至2018年1月我院收治的使用CLAG方案±地西他滨治疗的7例难治、复发AML患者,观察其疗效和不良反应,并进行随访。收集国内关于CLAG方案治疗复发、难治AML的相关文献,进行综合分析。结果:7例患者经CLAG方案±地西他滨化学治疗(化疗)1个疗程后, 4例完全缓解(complete remission,CR),3例未缓解(non-remission,NR)。主要不良反应为骨髓抑制(7例),血流感染、肠道感染和消化道出血各1例,无化疗相关死亡。4例CR与2例NR患者行异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)。最终选入5篇文献进行分析,CR率在34.6%～78.8%之间,加上本研究7例患者共104例, CR患者为61例。结论:CLAG方案对难治、复发AML有效,化疗所致骨髓抑制较重,但安全性良好,患者可耐受。一旦获得CR,尽快行allo-HSCT以延长生存期。
Objective To evaluate the efficacy, safety and adverse effect of CLAG [cladribine+cytarabine(Ara-C)+granulocyte colony stimulating factor(G-CSF)] regimen in patients with refractory or relapsed acute myeloid leukemia(AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML treated with CLAG along with decitabine from July 2015 through January 2018 were retrospectively analyzed with further follow up and literature review. Results Among 7 patients with refractory or relapsed AML investigated, the CLAG±decitabine regimen induced complete remission(CR) in 4 and yield no response(NR) in other 3 patients.Myelosuppression was the major side-effect(n=7), leading to blood stream infection(1 case), intestinal infection(1 case) and gastrointestinal bleeding(1 case). None of patients died from chemotherapy. Four CR patients and two NR patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT) thereafter. Analysis combining data extracted from domestic literature showed that the regimen achieved CR in 60 out of 104 patients in same condition as current study, and CR rate recorded ranging from 34.6% to 78.8%. Conclusions The CLAG regimen is an effective therapy for refractory or relapsed AML. The treatment is relatively safe with no fatal compli-cations, although sever marrow suppression is commonly observed. Allo-HSCT should be considered as soon as possible when patients achieved CR.
Objective To evaluate the efficacy, safety and adverse effect of CLAG [cladribine+cytarabine(Ara-C)+granulocyte colony stimulating factor(G-CSF)] regimen in patients with refractory or relapsed acute myeloid leukemia(AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML treated with CLAG along with decitabine from July 2015 through January 2018 were retrospectively analyzed with further follow up and literature review. Results Among 7 patients with refractory or relapsed AML investigated, the CLAG±decitabine regimen induced complete remission(CR) in 4 and yield no response(NR) in other 3 patients.Myelosuppression was the major side-effect(n=7), leading to blood stream infection(1 case), intestinal infection(1 case) and gastrointestinal bleeding(1 case). None of patients died from chemotherapy. Four CR patients and two NR patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT) thereafter. Analysis combining data extracted from domestic literature showed that the regimen achieved CR in 60 out of 104 patients in same condition as current study, and CR rate recorded ranging from 34.6% to 78.8%. Conclusions The CLAG regimen is an effective therapy for refractory or relapsed AML. The treatment is relatively safe with no fatal compli-cations, although sever marrow suppression is commonly observed. Allo-HSCT should be considered as soon as possible when patients achieved CR.
引文
[1]Price SL,Lancet JE,George TJ,et al.Salvage chemotherapy regimens for acute myeloid leukemia:is one better?[J].Leuk Res,2011,35(3):301-304.
[2]Wrzesień-Kués A,Robak T,Lech-Marańda E,et al.Amulticenter,open,non-comparative,phaseⅡstudy of the combination of cladribine(2-chlorodeoxyadenosine),cytarabine,and G-CSF as induction therapy in refractory acute myeloid leukemia-a report of the Polish Adult Leukemia Group(PALG)[J].Eur J Haematol,2003,71(3):155-162.
[3]Mike MG,John WS,Kistan M,et al.Cladribine in the treatment of acute myeloid leukemia:a single-institution experience[J].Clin Lymphoma Myeloma,2009,9(4):298-301.
[4]张之南,沈悌.血液病诊断及疗效标准[M].3版,北京科学出版社,2007:131-134.
[5]中华医学会血液学分会白血病淋巴瘤学组.复发难治性急性髓系白血病中国诊疗指南(2017年版)[J].中华血液学杂志,2017,38(3):183-184.
[6]高飞,杜明珠,李光.CLAG方案治疗复发难治急性髓系白血病的疗效观察[J].现代肿瘤医学,2018,26(7):1075-1078.
[7]段明辉,张岩,张梅,等.CLAG方案治疗33例难治复发急性髓系白血病的疗效及安全性[J].中华血液学杂志,2016,37(7):571-575.
[8]周海侠,胡晓慧,吴德沛,等.克拉屈滨联合化疗对于复发/难治急性髓细胞白血病的疗效观察[J].中国血液流变学杂志,2015,25(3):279-285.
[9]李光,任婧婧,李罡灿,等.CLAG方案和MEA方案治疗复发/难治急性髓系白血病的疗效比较[J].现代肿瘤医学,2018,26(2):264-268.
[10]刘莹,米瑞华,陈琳,等.CLAG方案治疗复发难治急性髓系白血病六例并文献复习[J].白血病·淋巴瘤,201827(7):415-417.
[11]D觟hner H,Weisdorf DJ,Bloomfield CD.Acute myeloid leukemia[J].N Engl J Med,2015,373(12):1136-1152.
[12]Ramos NR,Mo CC,Karp JE,et al.Current approaches in the treatment of relapsed and refractory acute myeloid leukemia[J].J Clin Med,2015,4(4):665-695.
[13]Robak T,Wierzbowska A.Cladribine in the treatment of acute myeloid leukemia[J].Leuk Res,2014,38(4):425-427.
[14]Robak P,Robak T.Older and new purine nucleoside analogs for patients with acute leukemias[J].Cancer Treat Rev,2013,39(8):851-861.
[15]Miyawaki S,Kawai Y,Takeshita A,et al.PhaseⅠtrial of FLAGM with high doses of cytosine arabinoside for relapsed,refractory acute myeloid leukemia:study of the Japan Adult Leukemia Study Group(JALSG)[J].Int JHematol,2007,86(4):343-347.
[16]Liongue C,Ward AC.Granulocyte colony-stimulating factor receptor mutations in myeloid malignancy[J].Front Oncol,2014,4:93.
[17]Robak T,Wrzesień-Kués A,Lech-Marańda E,el a1.Combination regimen of cladribine(2-chlorodeoxyadenosine),cytarabine and G-CSF(CLAG)as induction therapy for patients with relapsed or refractory acute myeloid leukemia[J].Leuk Lymphoma,2000,39(1-2):121-129.
[18]Kim HJ,Park EK,Moon IS.A case of sudden hearing loss during treatment with decitabine for chronic myelomonocytic leukemia[J].Chin J Cancer Res,2014,26(1):E1.
[19]Momparler RL,C?téS,Momparler LF.Epigenetic action of decitabine(5-aza-2’-deoxycytidine)is more effective against acute myeloid leukemia than cytotoxic action of cytarabine(ARA-C)[J].Leuk Res,2013,37(8):980-984.
[2]Wrzesień-Kués A,Robak T,Lech-Marańda E,et al.Amulticenter,open,non-comparative,phaseⅡstudy of the combination of cladribine(2-chlorodeoxyadenosine),cytarabine,and G-CSF as induction therapy in refractory acute myeloid leukemia-a report of the Polish Adult Leukemia Group(PALG)[J].Eur J Haematol,2003,71(3):155-162.
[3]Mike MG,John WS,Kistan M,et al.Cladribine in the treatment of acute myeloid leukemia:a single-institution experience[J].Clin Lymphoma Myeloma,2009,9(4):298-301.
[4]张之南,沈悌.血液病诊断及疗效标准[M].3版,北京科学出版社,2007:131-134.
[5]中华医学会血液学分会白血病淋巴瘤学组.复发难治性急性髓系白血病中国诊疗指南(2017年版)[J].中华血液学杂志,2017,38(3):183-184.
[6]高飞,杜明珠,李光.CLAG方案治疗复发难治急性髓系白血病的疗效观察[J].现代肿瘤医学,2018,26(7):1075-1078.
[7]段明辉,张岩,张梅,等.CLAG方案治疗33例难治复发急性髓系白血病的疗效及安全性[J].中华血液学杂志,2016,37(7):571-575.
[8]周海侠,胡晓慧,吴德沛,等.克拉屈滨联合化疗对于复发/难治急性髓细胞白血病的疗效观察[J].中国血液流变学杂志,2015,25(3):279-285.
[9]李光,任婧婧,李罡灿,等.CLAG方案和MEA方案治疗复发/难治急性髓系白血病的疗效比较[J].现代肿瘤医学,2018,26(2):264-268.
[10]刘莹,米瑞华,陈琳,等.CLAG方案治疗复发难治急性髓系白血病六例并文献复习[J].白血病·淋巴瘤,201827(7):415-417.
[11]D觟hner H,Weisdorf DJ,Bloomfield CD.Acute myeloid leukemia[J].N Engl J Med,2015,373(12):1136-1152.
[12]Ramos NR,Mo CC,Karp JE,et al.Current approaches in the treatment of relapsed and refractory acute myeloid leukemia[J].J Clin Med,2015,4(4):665-695.
[13]Robak T,Wierzbowska A.Cladribine in the treatment of acute myeloid leukemia[J].Leuk Res,2014,38(4):425-427.
[14]Robak P,Robak T.Older and new purine nucleoside analogs for patients with acute leukemias[J].Cancer Treat Rev,2013,39(8):851-861.
[15]Miyawaki S,Kawai Y,Takeshita A,et al.PhaseⅠtrial of FLAGM with high doses of cytosine arabinoside for relapsed,refractory acute myeloid leukemia:study of the Japan Adult Leukemia Study Group(JALSG)[J].Int JHematol,2007,86(4):343-347.
[16]Liongue C,Ward AC.Granulocyte colony-stimulating factor receptor mutations in myeloid malignancy[J].Front Oncol,2014,4:93.
[17]Robak T,Wrzesień-Kués A,Lech-Marańda E,el a1.Combination regimen of cladribine(2-chlorodeoxyadenosine),cytarabine and G-CSF(CLAG)as induction therapy for patients with relapsed or refractory acute myeloid leukemia[J].Leuk Lymphoma,2000,39(1-2):121-129.
[18]Kim HJ,Park EK,Moon IS.A case of sudden hearing loss during treatment with decitabine for chronic myelomonocytic leukemia[J].Chin J Cancer Res,2014,26(1):E1.
[19]Momparler RL,C?téS,Momparler LF.Epigenetic action of decitabine(5-aza-2’-deoxycytidine)is more effective against acute myeloid leukemia than cytotoxic action of cytarabine(ARA-C)[J].Leuk Res,2013,37(8):980-984.