益髓颗粒治疗骨髓增生异常综合征的临床观察

【作者】 李洁；

【导师】 李忠；

【作者基本信息】 北京中医药大学 ， 中西医结合临床， 2012， 博士

【摘要】 骨髓增生异常综合征(Myelodysplastic Syndrome, MDS)是一种造血干/祖细胞的恶性克隆增殖性疾病。临床以骨髓增生活跃或明显活跃,伴有无效和病态造血,以及周围血象一系或一系以上呈不同程度减少,并由此导致贫血、出血和感染为特征。在MDS病变自然发展过程中有两种转化趋势,一是由于感染、出血等因素导致临床死亡；二是转化为急性白血病。MDS的发病率随着年龄的增加而增高,但是近些年来由于骨髓活组织检查的临床应用以及分子生物学诊断技术发展,MDS发生与检出率日益增多,青少年和儿童的发病率也有逐渐增多的趋势。其主要西医治疗手段有：支持治疗、免疫抑制/免疫调节剂治疗、化疗、异基因造血干细胞移植(allo-HSCT)。鉴于MDS独特的生物学特征及临床表现特点,国际工作组认为,治疗MDS的两大目标是减少因贫血、白细胞少、血小板低导致的相关并发症与提高患者的生存质量。并未奢望经治疗后外周血细胞和骨髓造血功能有明显改善及缓解治愈。目的：本研究探讨中药“益髓颗粒”对MDS患者的临床疗效,观察其在稳定外周血象、改善临床症状及生活质量、减少输血量及频次方面有无作用。方法：依据临床研究方案,研究对象为2010年12月至2011年12月期间在北京中医药大学东直门医院血液肿瘤科病房或者门诊就诊的MDS患者。纳入30例符合以下纳入标准的患者：病程大于3个月；中医辨证属气阴两虚、血瘀内阻；年龄在18～80岁之间；未参加其它临床研究；患者本人同意。收集患者入组前3个月的外周血象,以及入组前3个月的输血量及频次。患者入组时采集中医临床症状资料,检查血常规、骨髓象、以及安全性指标。入组后服用益髓颗粒,每次2袋,每天3次,连续服用12周。治疗第2周、4周、8周、12周进行随访,收集中医临床症状治疗,复查上述指标。分析结果由SPSS17.0软件产生,所有的统计均采用双侧检验,当P值小于或等于0.05时,被认为所检验的差别有统计学意义。采用t检验、wilcoxon检验等统计方法,比较患者治疗前后的中医临床症状、外周血象、骨髓象、输血情况、安全性指标,分析益髓颗粒的临床疗效以及安全性。结果：纳入的30例患者中,脱落1例,进入统计学分析者29例。①按照骨髓增生异常综合征临床疗效评定标准,29例患者中明显进步4例,占13.8%；进步15例,占51.7%；无效10例,占34.5%；总有效率为65.5%。②益髓颗粒治疗第4周、第8周和第12周中医临床症状总计分,与治疗前比较,均有统计学意义(P<0.01)。治疗第4周、第8周和第12周神疲懒言、体倦乏力、头晕症状与治疗前比较有明显改善(P<0.05)。治疗第8周、第12周口干咽燥计分、出血主症计分与治疗前比较有统计学意义(P<0.05)。治疗第12周五心烦热、血瘀主症与治疗前比较显著改善(P<0.05)。③入组前3月与入组时外周血象(白细胞计数、血红蛋白量、血小板计数)比较,均无显著差异(P>0.05)。④治疗第12周白细胞、血小板计数与治疗前比较有明显提高(P<0.05)。治疗第4周、第8周和第12周血红蛋白与治疗前比较显著升高(P<0.05)。中性粒细胞治疗前后无明显变化(P>0.05)。⑤30例患者中有14例在第12周复查了骨髓象。14例患者治疗前后骨髓增生情况比较无明显变化(P>0.05)；病态造血系数未见改变；其中2例RAEB型患者原始细胞计数无显著变化。⑥治疗后血小板输注量、红细胞输注量及红细胞输注次数与治疗前比较均有显著减少(P<0.05)。⑦MDS的国际预后积分系统(international Prognostic Scoring System, IPSS)低危组患者的临床疗效与中危-1组比较有统计学意义(P<0.05)。⑧女性出血症状的改善优于男性(P<O.05)。⑨治疗前后生化指标比较无明显变化(P>0.05)；心电图、胸片检查治疗前后无显著差异(P>0.05)；治疗过程中未发生不良反应。结论：①益髓颗粒能够改善低危MDS患者中医临床症状,提高其生活质量。单项症状中体倦乏力、神疲懒言、头晕症状改善的较快；五心烦热、瘀血主症改善较慢。②益髓颗粒能够稳定低危MDS患者外周血象。③由于本研究观察周期较短,益髓颗粒对MDS患者骨髓象的影响尚难以得到确切的结论,需要远期观察。④益髓颗粒能够减少低危MDS患者的红细胞输注量及频次,减少其血小板输注量,降低患者输血依赖程度。⑤益髓颗粒临床应用是安全的。总之,益髓颗粒可以改善低危MDS患者的临床症状与生活质量、稳定外周血象、减少输血量及频率,且临床应用安全。更多还原

【Abstract】 Objective:To discuss short term effect of the Chinese herb Yi Sui granule on myelodysplastic syndrome(MDS).To provide an effective treatment for MDS patients.To observe if Yi Sui granule can improve clinical symptoms of MDS patients;if it can stabilize peripheral hemogram of MDS patients;and if it can decrease the amount and frequency of blood transfusion.Methods:According to the design,the cases were from Hematology-oncology ward and ourpatient department of Dongzhimen hospital of Beijing University of Chinese Medicine from Dec of 2010 to Dec of 2011.In our clinical research,30 cases of MDS were brought into the investigation. In all the cases,24g of Yi Sui granule were administered orally three times daily for 12 weeks. After 12 weeks we analysed the the clinical efficiency of the Yi Sui granule from the clinical symptoms,peripheral hemogram,myelogram,blood transfusion, security, etc.Results:29 cases were enrolled in the analysis of results with 1 case of deletion.(1)4 out of 30 patients had an significantly improvement(13.8%);15 patients had an improvement(51.7%); 10 patients had no response(34.7%).The total effective rate was 65.5%.(2)The patients’clinical symptoms were improved singifaicantly than those before treatment in the fourth,eighth and twelfth week(P<0.01).All the single symptoms were improved than those before treatment(P<0.01),especially tiredness,shortness of breath,hypodynamia and dizziness.(3)In the twelfth week the patient’s hemoglobin count(x±s) increased from (78.97±23.16)g/L to (92.1±20.93)g/L(P<0.01);the blood platelet count(x±s) increased from (64.38±57.08)×109/L to (67.76±53.16)×109/L(P<0.05);the leukocyte count(x±s) increased from (1.55±0.96)×109/L to (1.61±0.93)×109/L (P<0.05).(4)14 cases out of the 29 patients had myelogram reexamination.The bone marrow proliferation demonstrated no improvement(P>0.05).(5)The frequency of the RBC transfusion,the amount of RBC and platelet transfusion were decreased than those before treatment(P<0.05).(6)The hemorrhagic symptoms of femals were improved better than that of males.(7)The patients of lower IPSS scores compared with those of higher IPSS scores had better clinical effect(P<0.05).(8)There was no adverse reaction during the research.Conclusion:1.Yi Sui granule was effective on improving the clinical symptoms of low risk MDS.2.It improved the peripheral hemogram especially the hemoglobin count of low risk MDS.3.The myelogram wasn’t improved during short term.4.It reduced the amount and frequency of RBC transfusion;it decreased the amount of platelet transfusion of low risk MDS.5.There wasn’t any adverse reaction during the course. It possessed good safety.更多还原