地西他滨联合低强度化疗与IA方案治疗新诊断老年急性髓细胞白血病的临床疗效对比
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摘要
目的回顾性分析地西他滨联合低强度化疗治疗新诊断的老年急性髓细胞白血病(AML)的临床疗效及不良反应,并与IA(3+7)方案对比。方法收集2015年2月至2017年4月在西安交通大学第一附属医院血液科住院的新诊断老年(年龄≥60岁)AML[急性早幼粒细胞白血病(APL)除外]患者24例,按照患者所采用的化疗方案分为地西他滨联合低强度化疗组(地西他滨组,14例)以及IA方案诱导化疗组(IA组,10例)。地西他滨组具体方案为:地西他滨剂量为15 mg·m~(-2)·d~(-1),连用5 d,低强度化疗主要为CAG方案[阿克拉霉素、阿糖胞苷和粒细胞集落刺激因子(G-CSF)],或减半剂量的DA方案(柔红霉素和阿糖胞苷);IA组方案为伊达比星8 mg·m~(-2)·d~(-1),连用3 d,阿糖胞苷100 mg·m~(-2)·d~(-1),连用7 d。回顾性分析二者的疗效及不良反应。结果地西他滨组14例患者中,7例获完全缓解(CR),2例获部分缓解(PR)。IA组10例患者中,4例获CR,2例获PR,1例发生治疗相关死亡。地西他滨组CR率较IA组略高(50.00%vs 40.00%,P=0.697),总有效率(ORR)较IA组略高,但差异均无统计学意义(64.29%vs 60.00%,P=1.000)。在地西他滨组,继发AML(骨髓增生异常综合征转化的)的CR率(60.00%vs 44.44%,P=1.000)和ORR较原发AML有所上升(80.00%vs 55.56%,P=0.580),但差异无统计学意义;男性患者的CR率明显低于女性患者(14.29%vs 85.71%,P=0.030)。两组患者均出现重度血液学毒性不良反应,骨髓抑制期间感染率地西他滨组较IA组有所降低,但差异无统计学意义(50.00%vs 90.00%,P=0.079)。结论对于年龄≥60岁新诊断的老年AML患者,地西他滨联合低强度化疗相比IA(3+7)方案有提高CR率、降低重度血液学毒性不良反应的趋势,但能否获得有统计学意义的变化,有待扩大样本量进一步探讨。
Objective To study the clinical efficacy and adverse reactions of decitabine combined with low intensity chemotherapy retrospectively and compare with IA regimen(3+7) in the treatment of newly diagnosed elderly acute myeloid leukemia(AML).Methods Twenty-four senile patients(≥60 years old) with newly diagnosed AML [except acute promyelocytic leukemia(APL)] in the Department of Hematology,First Affiliated Hospital of Xi′an Jiaotong University from February 2015 to April 2017 were selected and divided into decitabine group(n=14) and IA group(n=10).In decitabine group,single-day dose of decitabine 15 mg·m~(-2)·d~(-1) for 5 days and low-intensity chemotherapy,mainly CAG regimen [aclacinomycin,cytarabine,granulocyte colony-stimulating factor(G-CSF)] or half-dose DA regimen(daunorubicin and cytarabine) were given.In IA group,idarubicin 8 mg·m~(-2)·d~(-1) for 3 days and cytarabine 100 mg·m~(-2)·d~(-1) for 7 days were given.The efficacy and adverse reactions were retrospectively analyzed in two groups.Results In decitabine group,7 patients achieved complete remission(CR),and 2 patients achieved partial remission(PR).In IA group,4 patients achieved CR,2 patients achieved PR,and one patient died of treatment-related death.Even though the CR rate(50.00% vs 40.00%,P=0.697) and total effective rate(ORR)(64.29% vs 60.00%,P=1.000) were slightly higher in decitabine group than those in IA group,there were no statistical differences between two groups.In decitabine group,CR rate(60.00% vs 44.44%,P=1.000),and ORR(80.00% vs 55.56%,P=0.580) of secondary AML(transformation from myelodysplastic syndrome) were higher than those of primary AML,but there were no significant differences between two groups;CR rate of male patients was significantly lower than that of female patients(14.29% vs 85.71%,P=0.030).Severe hematological toxicity adverse reactions were observed in both groups.The infection rate during bone marrow suppression in decitabine group was lower than that in IA group,but there was no statistical difference between two groups(50.00% vs 90.00%,P=0.079).Conclusions Compared with IA(3+7) regimen,decitabine combined with low-intensity chemotherapy has a tendency to improve complete remission rate and reduce severe hematological toxicity adverse reactions in newly diagnosed AML patients aged≥60 years.Whether statistical changes can be obtained,it remains to be further explored by enlarging the sample size.
Objective To study the clinical efficacy and adverse reactions of decitabine combined with low intensity chemotherapy retrospectively and compare with IA regimen(3+7) in the treatment of newly diagnosed elderly acute myeloid leukemia(AML).Methods Twenty-four senile patients(≥60 years old) with newly diagnosed AML [except acute promyelocytic leukemia(APL)] in the Department of Hematology,First Affiliated Hospital of Xi′an Jiaotong University from February 2015 to April 2017 were selected and divided into decitabine group(n=14) and IA group(n=10).In decitabine group,single-day dose of decitabine 15 mg·m~(-2)·d~(-1) for 5 days and low-intensity chemotherapy,mainly CAG regimen [aclacinomycin,cytarabine,granulocyte colony-stimulating factor(G-CSF)] or half-dose DA regimen(daunorubicin and cytarabine) were given.In IA group,idarubicin 8 mg·m~(-2)·d~(-1) for 3 days and cytarabine 100 mg·m~(-2)·d~(-1) for 7 days were given.The efficacy and adverse reactions were retrospectively analyzed in two groups.Results In decitabine group,7 patients achieved complete remission(CR),and 2 patients achieved partial remission(PR).In IA group,4 patients achieved CR,2 patients achieved PR,and one patient died of treatment-related death.Even though the CR rate(50.00% vs 40.00%,P=0.697) and total effective rate(ORR)(64.29% vs 60.00%,P=1.000) were slightly higher in decitabine group than those in IA group,there were no statistical differences between two groups.In decitabine group,CR rate(60.00% vs 44.44%,P=1.000),and ORR(80.00% vs 55.56%,P=0.580) of secondary AML(transformation from myelodysplastic syndrome) were higher than those of primary AML,but there were no significant differences between two groups;CR rate of male patients was significantly lower than that of female patients(14.29% vs 85.71%,P=0.030).Severe hematological toxicity adverse reactions were observed in both groups.The infection rate during bone marrow suppression in decitabine group was lower than that in IA group,but there was no statistical difference between two groups(50.00% vs 90.00%,P=0.079).Conclusions Compared with IA(3+7) regimen,decitabine combined with low-intensity chemotherapy has a tendency to improve complete remission rate and reduce severe hematological toxicity adverse reactions in newly diagnosed AML patients aged≥60 years.Whether statistical changes can be obtained,it remains to be further explored by enlarging the sample size.
引文
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[12] Blum W,Garzon R,Klisovic RB,et al.Clinical response and miR-29b/predictive significance in older AML patients treated with a 10-day schedule of decitabine[J].PNAS,2010,107(16):7473-7478.
[13] Cashen AF,Schiller GJ,O′Donnell MR,et al.Multicenter,phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia[J].J Clin Oncol,2010,28(4):556-561.
[14] Kantarjian HM,Thomas XG,Dmoszynska A,et al.Multicenter,randomized,open-label,phase Ⅲ trial of decitabine versus patient choice,with physician advice,of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia[J].J Clin Oncol,2012,30(21):2670-2677.
[2] Klepin HD.Myelodysplastic syndromes and acute myeloid leukemia in the elderly[J].Clin Geriatr Med,2016,32(1):155-173.
[3] Ohgami RS,Ma L,Merker JD,et al.Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53,U2AF1,ASXL1,and TET2 mutations[J].Mod Pathol,2015,28(5):706-714.
[4] Jiang Y,Dunbar A,Gondek LP,et al.Aberrant DNA methylation is a dominant mechanism in MDS progression to AML[J].Blood,2009,113(6):1315-1325.
[5] Petti MC,Mandelli F,Zagonel V,et al.Pilot study of 5-aza-2′-deoxycytidine (Decitabine) in the treatment of poor prognosis acute myelogenous leukemia patients:preliminary results[J].Leukemia,1993,7 Suppl 1:36-41.
[6] Jones PA,Taylor SM.Cellular differentiation,cytidine analogs and DNA methylation[J].Cell,1980,20(1):85-93.
[7] Bacher U,Kern W,Schnittger S,et al.Population-based age-specific incidences of cytogenetic subgroups of acute myeloid leukemia[J].Haematologica,2005,90(11):1502-1510.
[8] Al-Salihi M,Yu M,Burnett DM,et al.The depletion of DNA methyltransferase-1 and the epigenetic effects of 5-aza-2′deoxycytidine (decitabine) are differentially regulated by cell cycle progression[J].Epigenetics,2011,6(8):1021-1028.
[9] Chowdhury S,Seropian S,Marks PW.Decitabine combined with fractionated gemtuzumab ozogamicin therapy in patients with relapsed or refractory acute myeloid leukemia[J].Am J Hematol,2009,84(9):599-600.
[10] Momparler RL.Pharmacology of 5-Aza-2′-deoxycytidine (decitabine)[J].Semin Hematol,2005,42(3 Suppl 2):S9-S16.
[11] Herman JG,Baylin SB.Gene silencing in cancer in association with promoter hypermethylation[J].N Engl J Med,2003,349(21):2042-2054.
[12] Blum W,Garzon R,Klisovic RB,et al.Clinical response and miR-29b/predictive significance in older AML patients treated with a 10-day schedule of decitabine[J].PNAS,2010,107(16):7473-7478.
[13] Cashen AF,Schiller GJ,O′Donnell MR,et al.Multicenter,phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia[J].J Clin Oncol,2010,28(4):556-561.
[14] Kantarjian HM,Thomas XG,Dmoszynska A,et al.Multicenter,randomized,open-label,phase Ⅲ trial of decitabine versus patient choice,with physician advice,of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia[J].J Clin Oncol,2012,30(21):2670-2677.