目的:探讨原发性血小板增多症(ET)JAK2、CALR、MPL基因突变及阴性突变患者的临床特点。方法:选取2016年01月至2018年12月在南京医科大学附属淮安第一医院血液科住院确诊的66例ET患者,录入患者的性别、年龄、临床症状、有无血栓事件、脾...目的:探讨原发性血小板增多症(ET)JAK2、CALR、MPL基因突变及阴性突变患者的临床特点。方法:选取2016年01月至2018年12月在南京医科大学附属淮安第一医院血液科住院确诊的66例ET患者,录入患者的性别、年龄、临床症状、有无血栓事件、脾大、血小板数(Plt)、白细胞数(WBC)、血红蛋白(Hb)、纤维蛋白原(FIB)、血栓弹力图(TEG)、血钾、血糖(GLU)、乳酸脱氢酶(LDH)以及JAK2、CALR和MPL基因突变,治疗方案及疗效。对以上数据进行统计分析。结果:所有患者MPL突变阴性,故根据基因突变分为3组,JAK2突变组(46例,69.7%)、CALR突变组(9例,13.6%)和基因阴性组(11例,16.7%)。JAK2突变组患者的平均发病年龄为63.2岁,与CALR突变组(51.8岁)和基因阴性组(50.2岁)相比,具有显著的统计学差异(P<0.05)。CALR突变组与JAK2突变组、基因阴性组相对比,WBC数低(6.3×10^9/L vs 13.79×10^9/L,P=0.003;6.3×10^9/L vs 9.70×10^9/L,P=0.009);Hb水平较JAK2突变组低(121.22 g/L vs 136.2 g/L,P=0.036);但CALR突变组的肿瘤负荷较基因阴性组高(300.11 U/L vs 227.4 U/L,P=0.033);3组之间的Plt数、血钾水平、GLU及FIB水平无统计学差异(P>0.05)。另外,30.3%(20/66)患者存在血栓及栓塞事件,18.2%(12/66)患者合并高钾血症,且高钾血症与Plt数具有显著的相关性(r=0.518)。34例患者给予TEG检查,其中41.2%(14/34)患者出现TEG异常,55.9%(19/34)同时伴有Plt数>1000×10^9/L,但2者之间无显著的相关性(r=0.134)。66例患者采用常规临床治疗方案后均达部分或完全血液学缓解,但有疾病反复,4.5%(3/66)进展为骨髓纤维化(MF),均为具有JAK2突变患者。暂无进展为急性髓系白血病的病例。结论:伴有JAK2突变的ET患者发病率更高、且年龄偏大,然而CALR突变阳性患者具有更低的WBC数与Hb水平,却具更高的肿瘤负荷。总之,ET患者多样化的基因突变类型具有不同的临床特征,且与患者预后密切相关,这为临床诊疗工作提供了一定的思路。展开更多
Background Homoharringtonine （HHT） is effective in treating late stage chronic myelogenous leukaemia （CML）, but little is known about long term maintenance during complete cytogenetic response. Long term efficacy ...Background Homoharringtonine （HHT） is effective in treating late stage chronic myelogenous leukaemia （CML）, but little is known about long term maintenance during complete cytogenetic response. Long term efficacy and toxicity profiles of low dose HHT were evaluated in this study. Methods One hundred and six patients with CML received 1.5 mg/m^2 of HHT alone by continuous daily infusion for seven to nine days every four weeks. Of 79 patients in the control group, 31 were treated with interferon α （IFN-α） and 48 with hydroxycarbamide. For 17 patients who failed to achieve cytogenetic response within 12 months＇ treatment of IFN-α, HHT was administered. Quantitative RT-PCR was used to detect the BCR-ABL mRNA expression in 36 Philadelphia positive CML patients enrolled after 2007. Haematological and cytogenetic responses were evaluated in all patients at the 12th month of follow-up. Long term efficacy was assessed in a follow-up with a median time of 54 months （12 months-98 months）. Results After 12 months of therapy, cytogenetic response rate of the HHT, IFN-α and hydroxycarbamide groups were 39/106, 14/31 and 3/48, and corresponding molecular cytogenetic response rates 6/18, 3/8 and 0. Of the 17 patients who received HHT as salvage treatment, 6 achieved cytogenetic response （3 major）. At the 48 months＇ follow-up, cytogenetic response was maintained in 32/39 patients treated with HHT. Patients who had cytogenetic response in HHT group or treated with IFN-α also showed longer median chronic durations, which were 45 months （12 months-98 months） and 49 months （12 months-92 months） respectively, indicating a longer survival time. Conclusions Low dose HHT alone showed considerable short term and long term efficacy in the treatment of late stage CML. It may also be a good choice for patients who have failed imatinib, IFN-α treatment or haematopoietic stem cell transplantation or cannot afford these treatments.展开更多
文摘目的:探讨原发性血小板增多症(ET)JAK2、CALR、MPL基因突变及阴性突变患者的临床特点。方法:选取2016年01月至2018年12月在南京医科大学附属淮安第一医院血液科住院确诊的66例ET患者,录入患者的性别、年龄、临床症状、有无血栓事件、脾大、血小板数(Plt)、白细胞数(WBC)、血红蛋白(Hb)、纤维蛋白原(FIB)、血栓弹力图(TEG)、血钾、血糖(GLU)、乳酸脱氢酶(LDH)以及JAK2、CALR和MPL基因突变,治疗方案及疗效。对以上数据进行统计分析。结果:所有患者MPL突变阴性,故根据基因突变分为3组,JAK2突变组(46例,69.7%)、CALR突变组(9例,13.6%)和基因阴性组(11例,16.7%)。JAK2突变组患者的平均发病年龄为63.2岁,与CALR突变组(51.8岁)和基因阴性组(50.2岁)相比,具有显著的统计学差异(P<0.05)。CALR突变组与JAK2突变组、基因阴性组相对比,WBC数低(6.3×10^9/L vs 13.79×10^9/L,P=0.003;6.3×10^9/L vs 9.70×10^9/L,P=0.009);Hb水平较JAK2突变组低(121.22 g/L vs 136.2 g/L,P=0.036);但CALR突变组的肿瘤负荷较基因阴性组高(300.11 U/L vs 227.4 U/L,P=0.033);3组之间的Plt数、血钾水平、GLU及FIB水平无统计学差异(P>0.05)。另外,30.3%(20/66)患者存在血栓及栓塞事件,18.2%(12/66)患者合并高钾血症,且高钾血症与Plt数具有显著的相关性(r=0.518)。34例患者给予TEG检查,其中41.2%(14/34)患者出现TEG异常,55.9%(19/34)同时伴有Plt数>1000×10^9/L,但2者之间无显著的相关性(r=0.134)。66例患者采用常规临床治疗方案后均达部分或完全血液学缓解,但有疾病反复,4.5%(3/66)进展为骨髓纤维化(MF),均为具有JAK2突变患者。暂无进展为急性髓系白血病的病例。结论:伴有JAK2突变的ET患者发病率更高、且年龄偏大,然而CALR突变阳性患者具有更低的WBC数与Hb水平,却具更高的肿瘤负荷。总之,ET患者多样化的基因突变类型具有不同的临床特征,且与患者预后密切相关,这为临床诊疗工作提供了一定的思路。
文摘Background Homoharringtonine （HHT） is effective in treating late stage chronic myelogenous leukaemia （CML）, but little is known about long term maintenance during complete cytogenetic response. Long term efficacy and toxicity profiles of low dose HHT were evaluated in this study. Methods One hundred and six patients with CML received 1.5 mg/m^2 of HHT alone by continuous daily infusion for seven to nine days every four weeks. Of 79 patients in the control group, 31 were treated with interferon α （IFN-α） and 48 with hydroxycarbamide. For 17 patients who failed to achieve cytogenetic response within 12 months＇ treatment of IFN-α, HHT was administered. Quantitative RT-PCR was used to detect the BCR-ABL mRNA expression in 36 Philadelphia positive CML patients enrolled after 2007. Haematological and cytogenetic responses were evaluated in all patients at the 12th month of follow-up. Long term efficacy was assessed in a follow-up with a median time of 54 months （12 months-98 months）. Results After 12 months of therapy, cytogenetic response rate of the HHT, IFN-α and hydroxycarbamide groups were 39/106, 14/31 and 3/48, and corresponding molecular cytogenetic response rates 6/18, 3/8 and 0. Of the 17 patients who received HHT as salvage treatment, 6 achieved cytogenetic response （3 major）. At the 48 months＇ follow-up, cytogenetic response was maintained in 32/39 patients treated with HHT. Patients who had cytogenetic response in HHT group or treated with IFN-α also showed longer median chronic durations, which were 45 months （12 months-98 months） and 49 months （12 months-92 months） respectively, indicating a longer survival time. Conclusions Low dose HHT alone showed considerable short term and long term efficacy in the treatment of late stage CML. It may also be a good choice for patients who have failed imatinib, IFN-α treatment or haematopoietic stem cell transplantation or cannot afford these treatments.
