高三尖杉酯碱与柔红霉素治疗急性早幼粒细胞白血病的对照研究
摘要
研究目的：
比较高三尖杉酯碱替代柔红霉素用于急性早幼粒细胞白血病(APL)治疗的疗效及安全性以探寻APL新的治疗策略。研究方法：
78例APL初诊患者随机分入柔红霉素(DNR)治疗组(42例)和高三尖杉酯碱(DNR)治疗组(36例),DNR组采用全反式维甲酸(ATRA)联合DNR诱导缓解,DNR及阿糖胞苷(Ara-c)巩固治疗两疗程,再以米托蒽醌(MTZ)及Ara-c巩固第三疗程,HHT组以HHT替代DNR和MTZ,其余用药与DNR组相同,此后两组患者均进入ATRA、6-MP、MTX维持治疗。进行临床资料分析,并收集每疗程治疗后骨髓单个核细胞以半定量逆转录-聚合酶连反应(RT-PCR)、实时定量RT-PCR法检测PML/RARα mRNA表达水平,从两组患者分子生物学缓解率、每个疗程结束后PML/RARα表达水平、中枢神经系统白血病发生率、诱导缓解治疗中维甲酸综合症发生率、出血风险、心脏毒副作用发生率对比DNR和HHT用于急性早幼粒细胞治疗的疗效及安全性。
结果：
入组时两组患者基线特征类似。HHT治疗APL诱导缓解治疗后、第一疗程巩固化疗后、第二疗程巩固治疗后巢式RT-PCR法分子生物学缓解率分别为28.57%、82.86%和100%,而DNR治疗APL诱导缓解治疗后、第一疗程巩固化疗后、第二疗程巩固治疗后巢式RT-PCR法分子生物学缓解率分别为35.71%、75.61%和97.44%,两组间各数据比较p>0.05。第三疗程巩固治疗后两组均全部分子生物学缓解率均为100%。HHT组和DNR组中枢神经系统白血病发生率分别为8.57%和12.52%(p>0.05),凝血功能异常持续时间分别为15.28±10.33天和17.85±9.71天(p>0.05),输血浆数分别为和25.3(0-75.6)ml/kg和17.3(0-123.4)ml/kg(p>0.05),维甲酸综合症发生率分别为2.86%和14.27%(p>0.05),非一过性心脏毒副作用发生率分别为9.68%和13.89%(p>0.05),诱导缓解后HHT组和DNR组PML/RAR a mRNA表达水平指标NQ值的中位数分别为3.76和5.56(p>0.05),第一疗程巩固化疗后两组PML/RARα mRNA NQ值中位数分别为0和0.25(p<0.05),第二和第三疗程疗程巩固化疗后两组PML/RARα mRNANQ中位数值均为0。巩固治疗两组均给予ATRA、MTX、6-MP维持治疗,DNR组随访中位时间18月(1-45月),HHT组随访中位时间22月(1-69月),复发率分别为2.56%和3.03%。
结论：
HHT治疗急性早幼粒细胞白血病在临床疗效和分子生物学缓解作用上与DNR相似,且不增加治疗相关副作用和并发症发生率,可用于治疗急性早幼粒细胞白血病。
Objective:
To compare effect and safety of HHT with DNR in treating acute promyelocytic leukemia
Method:
Seventy-eight newly diagnosed APL subjects were randomized into two treatment groups namely by HHT and DNR.Patients in DNR group were given ATRA and DNR for induction therapy, then two courses of consolidation treatment of DNR and Ara-c followed.In the third course of consolidation treatment they were given MTZ and Ara-c. Drugs of the HHT group are the same except HHT was used to take the place of DNR. All patients' clinical information was analyzed. Bone marrow mononuclear cells were collected after every course ended. Tumor burden was assessed by copies of PML/RARa fusion transcripts, which was examined by real-time quantitative RT-PCR. Molecular remission ratio, incidence rate of central nervous system leukemia and retinoic syndrome, resistance of blood cougulation disturbance and incidence rate of cardiac toxicity was compared between the two groups to disclose the difference in effect or safety of the two antitumor drug when prescribed to APL.
Results:
The molecular remission ratio of the HHT group after induction treatment and after the first and the second course of consolidation treatment were28.57%,82.86%and100%,100%, respectively. Those of the DNR group were35.71%,75.61%and97.44%, respectively (p>0.05). Median copies of PML/RARa fusion transcripts (presented by NQ value) after induction treatment of the HHT group and the DNR group were3.76and5.56respectively (p>0.05). Median copies of PML/RARa fusion transcripts after the first course of consolidation treatment of the HHT group and the DNR group were0and0.25respectively (p<0.05).At the end of the second and the third course of consolidation treatment those were both0in two groups (p>0.05).The incidence rate of central nervous system leukemia was8.57%in the HHT group, and the percent was12.52%in the DNR group (p>0.05). The incidence rate of retinoic syndrome was2.56%in the HHT group,and14.29%in the DNR group (p>0.05).The persistence time of blood cougulation disturbance and the plasma transfusion amount(ml/kg) of the HHT group were15.28±10.33d and25.3(0-75.6) ml/kg respectively, and those of the DNR group were17.85±9.71d and17.3(0-123.4) ml/kg respectively (p>0.05). The incidence ratio of untemporary cardiac toxicity event in the HHT group was9.68%, and it was13.89%in the DNR group(p>0.05). Thirty-nine from the DNR group and thirty-three from the HHT group were followed up for a median time of18month (1-45months) and22months(1-69months) respectively.They were all given ATRA,6-MP, MTX as resistance treatment. Replase rate during following up is3.03%in the HHT group and2.56%in the DNR group.
Conclusion:
HHT brings effects as good as DNR to APL patients without any more side effects. It can be used to treat APL.
比较高三尖杉酯碱替代柔红霉素用于急性早幼粒细胞白血病(APL)治疗的疗效及安全性以探寻APL新的治疗策略。研究方法：
78例APL初诊患者随机分入柔红霉素(DNR)治疗组(42例)和高三尖杉酯碱(DNR)治疗组(36例),DNR组采用全反式维甲酸(ATRA)联合DNR诱导缓解,DNR及阿糖胞苷(Ara-c)巩固治疗两疗程,再以米托蒽醌(MTZ)及Ara-c巩固第三疗程,HHT组以HHT替代DNR和MTZ,其余用药与DNR组相同,此后两组患者均进入ATRA、6-MP、MTX维持治疗。进行临床资料分析,并收集每疗程治疗后骨髓单个核细胞以半定量逆转录-聚合酶连反应(RT-PCR)、实时定量RT-PCR法检测PML/RARα mRNA表达水平,从两组患者分子生物学缓解率、每个疗程结束后PML/RARα表达水平、中枢神经系统白血病发生率、诱导缓解治疗中维甲酸综合症发生率、出血风险、心脏毒副作用发生率对比DNR和HHT用于急性早幼粒细胞治疗的疗效及安全性。
结果：
入组时两组患者基线特征类似。HHT治疗APL诱导缓解治疗后、第一疗程巩固化疗后、第二疗程巩固治疗后巢式RT-PCR法分子生物学缓解率分别为28.57%、82.86%和100%,而DNR治疗APL诱导缓解治疗后、第一疗程巩固化疗后、第二疗程巩固治疗后巢式RT-PCR法分子生物学缓解率分别为35.71%、75.61%和97.44%,两组间各数据比较p>0.05。第三疗程巩固治疗后两组均全部分子生物学缓解率均为100%。HHT组和DNR组中枢神经系统白血病发生率分别为8.57%和12.52%(p>0.05),凝血功能异常持续时间分别为15.28±10.33天和17.85±9.71天(p>0.05),输血浆数分别为和25.3(0-75.6)ml/kg和17.3(0-123.4)ml/kg(p>0.05),维甲酸综合症发生率分别为2.86%和14.27%(p>0.05),非一过性心脏毒副作用发生率分别为9.68%和13.89%(p>0.05),诱导缓解后HHT组和DNR组PML/RAR a mRNA表达水平指标NQ值的中位数分别为3.76和5.56(p>0.05),第一疗程巩固化疗后两组PML/RARα mRNA NQ值中位数分别为0和0.25(p<0.05),第二和第三疗程疗程巩固化疗后两组PML/RARα mRNANQ中位数值均为0。巩固治疗两组均给予ATRA、MTX、6-MP维持治疗,DNR组随访中位时间18月(1-45月),HHT组随访中位时间22月(1-69月),复发率分别为2.56%和3.03%。
结论：
HHT治疗急性早幼粒细胞白血病在临床疗效和分子生物学缓解作用上与DNR相似,且不增加治疗相关副作用和并发症发生率,可用于治疗急性早幼粒细胞白血病。
Objective:
To compare effect and safety of HHT with DNR in treating acute promyelocytic leukemia
Method:
Seventy-eight newly diagnosed APL subjects were randomized into two treatment groups namely by HHT and DNR.Patients in DNR group were given ATRA and DNR for induction therapy, then two courses of consolidation treatment of DNR and Ara-c followed.In the third course of consolidation treatment they were given MTZ and Ara-c. Drugs of the HHT group are the same except HHT was used to take the place of DNR. All patients' clinical information was analyzed. Bone marrow mononuclear cells were collected after every course ended. Tumor burden was assessed by copies of PML/RARa fusion transcripts, which was examined by real-time quantitative RT-PCR. Molecular remission ratio, incidence rate of central nervous system leukemia and retinoic syndrome, resistance of blood cougulation disturbance and incidence rate of cardiac toxicity was compared between the two groups to disclose the difference in effect or safety of the two antitumor drug when prescribed to APL.
Results:
The molecular remission ratio of the HHT group after induction treatment and after the first and the second course of consolidation treatment were28.57%,82.86%and100%,100%, respectively. Those of the DNR group were35.71%,75.61%and97.44%, respectively (p>0.05). Median copies of PML/RARa fusion transcripts (presented by NQ value) after induction treatment of the HHT group and the DNR group were3.76and5.56respectively (p>0.05). Median copies of PML/RARa fusion transcripts after the first course of consolidation treatment of the HHT group and the DNR group were0and0.25respectively (p<0.05).At the end of the second and the third course of consolidation treatment those were both0in two groups (p>0.05).The incidence rate of central nervous system leukemia was8.57%in the HHT group, and the percent was12.52%in the DNR group (p>0.05). The incidence rate of retinoic syndrome was2.56%in the HHT group,and14.29%in the DNR group (p>0.05).The persistence time of blood cougulation disturbance and the plasma transfusion amount(ml/kg) of the HHT group were15.28±10.33d and25.3(0-75.6) ml/kg respectively, and those of the DNR group were17.85±9.71d and17.3(0-123.4) ml/kg respectively (p>0.05). The incidence ratio of untemporary cardiac toxicity event in the HHT group was9.68%, and it was13.89%in the DNR group(p>0.05). Thirty-nine from the DNR group and thirty-three from the HHT group were followed up for a median time of18month (1-45months) and22months(1-69months) respectively.They were all given ATRA,6-MP, MTX as resistance treatment. Replase rate during following up is3.03%in the HHT group and2.56%in the DNR group.
Conclusion:
HHT brings effects as good as DNR to APL patients without any more side effects. It can be used to treat APL.
引文
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