地西他滨序贯或同时联合“3+7”方案在45例初发急性髓系白血病中治疗效果分析
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摘要
目的探讨地西他滨(decitabine,DAC)不同时间点联合标准诱导方案治疗初发急性髓系白血病(acute myeloid leukemia,AML)的治疗效果与安全性。方法回顾性分析2012年6月至2018年3月收治的45例初治急性髓系白血病接受地西他滨联合"3+7"方案治疗的临床资料,其中序贯组29例,同时用药组16例,比较2组患者的治疗效果、生存期及不良反应等。结果 45例患者总有效率(overall response rate,ORR)[完全缓解(complete response,CR)+形态学CR伴不全血象恢复(CR with incomplete hematological recovery,CRi)+部分缓解(partial response,PR)]达75. 56%;其中CR/CRi率为55. 6%(25/45);序贯组与同时用药组的ORR分别为75. 9%与75. 0%,差异无统计学意义(χ2=0. 595,P=0. 842)。治疗≥4个疗程的患者共24例,ORR达91. 7%;序贯组17例,ORR为94. 1%;同时用药组7例,ORR为85. 7%。中位随访时间8个月,序贯组与同时用药组的总生存(overall survival,OS)分别为(7. 25±4. 61)个月vs (8. 48±5. 42)个月(P=0. 447)。两组最常见的不良反应为3级及以上血细胞减少和感染,以呼吸道感染最为常见,在治疗早期(第1～2疗程)较常见。首次诱导治疗结束后,序贯组3#4级骨髓抑制时间较同时用药组延长,主要表现为粒细胞缺乏,分别为15. 0 d vs 8. 5 d(P <0. 001);序贯组肛周、胃肠道以及皮肤软组织感染发生率较高,红细胞及血小板输注量也较同时用药组高,但差异无统计学意义(P> 0. 05)。结论地西他滨序贯或同时联合标准诱导方案疗AML的治疗效果相当,但同时用药组安全性较好,骨髓抑制期短、血细胞输注量较少,感染发生率较低。
Objective To compare the clinical efficacy and safety among decitabine combined standard induction regimen at different time points in treatment of acute myeloid leukemia( AML). Methods The clinical data of 45 AML patients enrolled from June 2012 to March 2018 were collected. The differences of clinical outcome and adverse events among the patients treated with decitabine sequentially or simultaneously with"3 + 7"regimen were analyzed. Results For 45 patients,the overall response rate( ORR) [complete response( CR) + CR with incomplete hematological recovery( CRi) + partial response( PR) ]was 75. 56%,CR/CRi was up to 55. 6%( 25/45);The ORR in the sequential and simultaneous group was 75. 9% and 75. 0%,respectively. However,there is no significant difference was observed among the two groups( P = 0. 842). Median followed-up time was 8 months,the overall survival( OS) of sequential group and simultaneous group was( 7. 25 ± 4. 61) months vs( 8. 48 ± 5. 42) months( P = 0. 447). Adverse events in the two groups were similar,mainly including cytopenia and infection,which were more common in the early stages of treatment. After the first induction treatment,the3/4 grade myelosuppression time in the sequential group was longer than that in the simultaneous treatment group,mainly manifested as agranulocytosis,which was 15. 0 d vs 8. 5 d( P < 0. 001),and the incidence of perianal,gastrointestinal and skin and soft tissue infection was increased. The median number of suspended red blood cells and platelet infused was higher in the sequential group( P > 0. 05).Conclusion Whenever in sequential group or simultaneous group,the induction efficacy of decitabine combined with chemotherapy were similar,but the simultaneous group had better safety,the duration of myelosuppression was shorter,mainly manifested as shortening of the granulosis period,less blood cell infusion,and a lower incidence of infection.
Objective To compare the clinical efficacy and safety among decitabine combined standard induction regimen at different time points in treatment of acute myeloid leukemia( AML). Methods The clinical data of 45 AML patients enrolled from June 2012 to March 2018 were collected. The differences of clinical outcome and adverse events among the patients treated with decitabine sequentially or simultaneously with"3 + 7"regimen were analyzed. Results For 45 patients,the overall response rate( ORR) [complete response( CR) + CR with incomplete hematological recovery( CRi) + partial response( PR) ]was 75. 56%,CR/CRi was up to 55. 6%( 25/45);The ORR in the sequential and simultaneous group was 75. 9% and 75. 0%,respectively. However,there is no significant difference was observed among the two groups( P = 0. 842). Median followed-up time was 8 months,the overall survival( OS) of sequential group and simultaneous group was( 7. 25 ± 4. 61) months vs( 8. 48 ± 5. 42) months( P = 0. 447). Adverse events in the two groups were similar,mainly including cytopenia and infection,which were more common in the early stages of treatment. After the first induction treatment,the3/4 grade myelosuppression time in the sequential group was longer than that in the simultaneous treatment group,mainly manifested as agranulocytosis,which was 15. 0 d vs 8. 5 d( P < 0. 001),and the incidence of perianal,gastrointestinal and skin and soft tissue infection was increased. The median number of suspended red blood cells and platelet infused was higher in the sequential group( P > 0. 05).Conclusion Whenever in sequential group or simultaneous group,the induction efficacy of decitabine combined with chemotherapy were similar,but the simultaneous group had better safety,the duration of myelosuppression was shorter,mainly manifested as shortening of the granulosis period,less blood cell infusion,and a lower incidence of infection.
引文
[1]中华医学会血液学分会.成人急性髓系白血病(非急性早幼粒细胞白血病)中国诊疗指南(2017年版)[J].中华血液学杂志,2017,38(3):177-182.
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[3] Arber D A,Orazi A,Hasserjian R,et al. The 2016 revision to the w orld health organization classification of myeloid neoplasmsand acute leukemia[J]. Blood,2016,127(20):2391-2405.
[4] NCCN. NCCN clinical practice guidelines in oncology acute myeloid leukemia(Version 2. 2018)[DB/OL].(2018-11-15). http://www. nccn. org.
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[6] Tamamyan G,Kadia T,Ravandi F,et al. Frontline treatment of acute myeloid leukemia in adults[J]. Crit Rev Oncol Hematol,2017,110:20-34.
[7]罗丽卿,彭振翼,司秀文,等.急性髓细胞白血病IDH基因突变临床特征及预后意义[J].中华肿瘤防治杂志,2017,24(21):1530-1533.
[8]徐兵,林志娟.老年急性髓性白血病的预后判断及治疗进展[J].中华肿瘤防治杂志,2016,23(17):1134-1137.
[9] Momparler R L. Pharmacology of 5-Aza-2'-deoxycytidine(decitabine)[J]. Semin Hematol,2005,42(3):S9-S16.
[10] Jeong S H,Kim Y J,Lee J H,et al. A prospective,multicenter,observational study of long-term decitabine treatment in patients w ith myelodysplastic syndrome[J]. Oncotarget,2015,6(42):44985-44994.
[11] Kim T K,Gore S D,Zeidan A M. Epigenetic therapy in acute myeloid leukemia:current and future directions[J].Semin Hematol,2015,52(3):172-183.
[12] Ritchie E K,Feldman E J,Christors P J,et al. Decitabine in patients with newlydiagnosed and relapsed acute myeloid leukemia[J]. Leuk Lymphoma,2013,54(9):2003-2007.
[13]苏杰.小剂量地西他滨及阿糖胞甘治疗中高危骨髓增生异常综合征临床效果[J].临床误诊误治,2018,31(3):77-80.
[14] Leonard S M,Perry T,Woodman C B,et al. Sequential treatment w ith cytarabineand decitabine has an increased anti-1eukemia effect compared to cytarabine alone inxenograft models of childhood acute myeloid leukemia[J].PLoS One,2014,9(1):e87475.
[15] Scandura J M,Roboz G J,Moh M,et al. Phase 1 study of epigenetic primingw ith decitabine prior to standard induction chemotherapy for patients w ith AM L[J]. Blood,2011,118(6):1472-1480.
[16] Kongfei L,Chao H,Chen M,et al. Sequential combination of decitabine and idarubicin synergistically enhances antileukemia effect follow ed by demethylating Wnt pathw ay inhibitor promoters and dow nregulating Wnt pathw ay nuclear target[J]. J Translat M ed,2014,12:167.
[17]杨凯,陈惠仁,何学鹏,等.地西他滨联合不同化疗方案治疗老年人急性髓系白血病的临床观察[J].白血病·淋巴瘤,2014,23(8):484-487.
[18]郝杰,王黎,王艳煜,等.地西他滨联合DAG方案等三种方案治疗复发、难治急性髓系白血病疗效的比较分析[J].中华血液学杂志,2014,35(6):481-485.
[2] Nieto M,Demolis P,Behanzin E,et al. The european medicines agency reviewof decitabine(dacogen)for the treatment of adult patients with acute myeloid leukemia:summary of the scientific assessment of the committee for medicinal products for human use[J]. Oncologist,2016,21(6):692-700.
[3] Arber D A,Orazi A,Hasserjian R,et al. The 2016 revision to the w orld health organization classification of myeloid neoplasmsand acute leukemia[J]. Blood,2016,127(20):2391-2405.
[4] NCCN. NCCN clinical practice guidelines in oncology acute myeloid leukemia(Version 2. 2018)[DB/OL].(2018-11-15). http://www. nccn. org.
[5] Cheson B D,Bennett J M,Kopecky K J,et al. Revised recommcndations of the international w orking group for diagnosis,standardization of response criteria,treatment outcomes,and reporting standards for therapeutic trials in acute myeloid leukemia[J]. J Clin Oncol,2003,21(24):4642-4649.
[6] Tamamyan G,Kadia T,Ravandi F,et al. Frontline treatment of acute myeloid leukemia in adults[J]. Crit Rev Oncol Hematol,2017,110:20-34.
[7]罗丽卿,彭振翼,司秀文,等.急性髓细胞白血病IDH基因突变临床特征及预后意义[J].中华肿瘤防治杂志,2017,24(21):1530-1533.
[8]徐兵,林志娟.老年急性髓性白血病的预后判断及治疗进展[J].中华肿瘤防治杂志,2016,23(17):1134-1137.
[9] Momparler R L. Pharmacology of 5-Aza-2'-deoxycytidine(decitabine)[J]. Semin Hematol,2005,42(3):S9-S16.
[10] Jeong S H,Kim Y J,Lee J H,et al. A prospective,multicenter,observational study of long-term decitabine treatment in patients w ith myelodysplastic syndrome[J]. Oncotarget,2015,6(42):44985-44994.
[11] Kim T K,Gore S D,Zeidan A M. Epigenetic therapy in acute myeloid leukemia:current and future directions[J].Semin Hematol,2015,52(3):172-183.
[12] Ritchie E K,Feldman E J,Christors P J,et al. Decitabine in patients with newlydiagnosed and relapsed acute myeloid leukemia[J]. Leuk Lymphoma,2013,54(9):2003-2007.
[13]苏杰.小剂量地西他滨及阿糖胞甘治疗中高危骨髓增生异常综合征临床效果[J].临床误诊误治,2018,31(3):77-80.
[14] Leonard S M,Perry T,Woodman C B,et al. Sequential treatment w ith cytarabineand decitabine has an increased anti-1eukemia effect compared to cytarabine alone inxenograft models of childhood acute myeloid leukemia[J].PLoS One,2014,9(1):e87475.
[15] Scandura J M,Roboz G J,Moh M,et al. Phase 1 study of epigenetic primingw ith decitabine prior to standard induction chemotherapy for patients w ith AM L[J]. Blood,2011,118(6):1472-1480.
[16] Kongfei L,Chao H,Chen M,et al. Sequential combination of decitabine and idarubicin synergistically enhances antileukemia effect follow ed by demethylating Wnt pathw ay inhibitor promoters and dow nregulating Wnt pathw ay nuclear target[J]. J Translat M ed,2014,12:167.
[17]杨凯,陈惠仁,何学鹏,等.地西他滨联合不同化疗方案治疗老年人急性髓系白血病的临床观察[J].白血病·淋巴瘤,2014,23(8):484-487.
[18]郝杰,王黎,王艳煜,等.地西他滨联合DAG方案等三种方案治疗复发、难治急性髓系白血病疗效的比较分析[J].中华血液学杂志,2014,35(6):481-485.