伴有胸腺瘤的重症肌无力患者环磷酰胺治疗的疗效评价

发布时间：2018-07-14 13:54

【摘要】：目的： 1.观察伴有胸腺瘤的重症肌无力患者(myasthenia gravis with thymoma，MGT)环磷酰胺（Cyclophosphamide，CTX）治疗的疗效及副作用； 2.探讨MGT使用CTX治疗前后重复频率电刺激（repetitive nerve stimulation，RNS）的变化规律。方法： 1.所有研究对象来源于2006年12月至2013年8月第二炮兵总医院神经内科就诊的MGT患者，经筛查共有62例MGT患者接受CTX治疗直至研究结束，男34例，女28例，纳入时最小年龄20岁，最大年龄78岁，平均年龄(46.29±11.672)岁，平均病程(49.53±37.49)月，其中A型胸腺瘤5例，AB型胸腺瘤4例，B1型胸腺瘤21例，B2型胸腺瘤15例，B3型胸腺瘤10例，B1、B2混合型5例，B2、B3混合型2例。入院时MG改良Osserman分型Ⅰ型6例，ⅡA型13例，ⅡB型24例，Ⅲ型9例，Ⅳ型10例。 2.予以CTX0.2g/次静滴2次/第一周，0.4g/次静滴2次/第二周，0.8g/次静滴1次/周至总量10g。用药开始前及结束后完善重症肌无力临床绝对评分及RNS检查。根据重症肌无力的临床绝对评分和临床相对评分评定疗效。国外多项回顾性研究认为B2型，B3型胸腺瘤比A型、AB型、B1型胸腺瘤更具侵袭性，而肿瘤的侵袭性是区分良恶性肿瘤的标准之一，因此将胸腺病理分型为A型，AB型，B1型分为恶性程度较低组，病理分型是B2型，B3型，B1、B2混合型，B2、B3混合型者分为恶性程度较高组，比较两组间疗效的差异性，并观察部分患者治疗前后RNS检查的变化规律。 3.疗效判定：评定临床绝对评分记录患者肌无力和易疲劳性的严重程度。根据MG的相对评分法评定疗效。具体计算方法为：重症肌无力临床相对计分=（治疗前总分－治疗后总分）/治疗前总分×100％，相对评分≥95％者为痊愈，80％～95％者为基本痊愈，50％～80％者为显效，25％～50％者为好转，≤25％者为无效。总有效率=（痊愈+基本痊愈+显效+好转）人数/入组人数。结果：（1）62例MGT患者使用CTX治疗前后临床绝对评分明显下降，差异有统计学意义，提示环磷酰胺治疗有效，临床治疗总有效率达85%（53/62）。（2）2组MGT患者临床相对评分分别记为(0.59±0.28)、(0.61±0.31)，差异无统计学意义。（3）本研究所使用的CTX治疗方法仅有白细胞轻度下降，恶心、呕吐，转氨酶轻度升高等副作用，，副作用轻微，患者耐受性好。（4）对其中23例患者RNS结果进行分析，治疗后RNS低频衰减幅度较治疗前显著减少，治疗前后的差异具有统计学意义，说明治疗有效。结论：（1）采用本方法治疗MGT患者安全有效，但是本研究中患者疗效的评定以CTX总量达到10g为节点，其中部分患者因临床仍有肌无力症状而继续使用CTX，之后的疗效评估尚需进一步研究。（2）CTX对不同病理分型胸腺瘤的疗效无统计学差异，提示胸腺瘤病理的分型可能与CTX治疗疗效无关，但是由于本研究样本量小，观察时间短， CTX疗效差异性可能尚未显现，有待加大样本量及延长观察时间。（3）CTX治疗后，患者RNS低频波幅衰减程度减少，与重症肌无力临床绝对评分好转相一致，因此可作为CTX治疗重症肌无力伴胸腺瘤患者疗效的监测指标。
[Abstract]:Objective:
1. to observe the efficacy and side effects of myasthenia gravis with thymoma (MGT) cyclophosphamide (Cyclophosphamide) in patients with thymoma.
2. to explore the changes of repetitive nerve stimulation (RNS) in MGT before and after CTX treatment.
Method:
1. all the subjects were derived from the MGT patients in the neurology department of the Second Artillery General Hospital from December 2006 to August 2013. There were 62 cases of MGT patients receiving CTX treatment until the end of the study. There were 34 males and 28 females. The minimum age was 20 years, the maximum age was 78, the average age was (46.29 + 11.672) years, and the average course of disease was 49.53 + 37.49 months. 5 cases of middle A thymoma, 4 cases of type AB thymoma, 21 cases of B1 thymoma, 15 cases of B2 thymoma, 10 cases of B3 thymoma, 5 cases of B2 mixed type, B2 and 2 B3 mixed type, MG modified Osserman classification I 6 cases, 13 cases of A type, 24 cases of A type, 9 cases of type III and 10 cases of type IV.
2. CTX0.2g/ intravenous drip for 2 times / first week, 0.4g/ drop for 2 times / second weeks, 0.8g/ time drop 1 times per week before and after the total of 10g. medication, the clinical absolute score and RNS examination of myasthenia gravis were perfected. The clinical absolute score and clinical relative score of myasthenia gravis were evaluated and the curative effect was determined. A number of foreign retrospective studies considered B2, B Type 3 thymoma is more invasive than type A, type AB, B1 type thymoma, and the invasiveness of the tumor is one of the criteria for differentiating benign and malignant tumors. Therefore, the thymus is classified as A, AB and B1 into low malignancy, and the pathological type is B2, B3, B1, B2 mixed and B2, and B3 mixed type is divided into higher level of malignant degree, compared with the two groups. The changes of RNS in some patients before and after treatment were observed.
3. evaluation of curative effect: evaluate the severity of myasthenia and fatigue of patients by clinical absolute score. According to the relative score of MG, the clinical relative score of myasthenia gravis = (total score before treatment) / total score before treatment (total score) / 100%, relative score of more than 95% were cured, 80% to 95% For the basic recovery, 50% to 80% were effective, 25% to 50% were improved and less than 25% were ineffective. The total effective rate = (recovery + basic recovery + improved + improvement) number / entry group.
Result:
(1) the clinical absolute score of 62 patients with MGT was significantly decreased before and after the use of CTX. The difference was statistically significant, suggesting that cyclophosphamide was effective and the total effective rate of clinical treatment was 85% (53/62).
(2) the clinical relative scores of the 2 groups of MGT patients were respectively (0.59 + 0.28), (0.61 + 0.31), and the difference was not statistically significant.
(3) the CTX treatment used in this study is only mild leukocyte reduction, nausea and vomiting, mild side effects of aminotransferase, mild side effects, and good tolerance.
(4) the results of RNS in 23 of the patients were analyzed. The low frequency attenuation amplitude of RNS was significantly reduced after treatment, and the difference before and after treatment was statistically significant, indicating that the treatment was effective.
Conclusion:
(1) the treatment of MGT patients with this method is safe and effective, but in this study, the evaluation of the curative effect of this study is that the total amount of CTX is 10g as the node, and some of the patients continue to use CTX because of the clinical myasthenia symptoms, and the evaluation of the curative effect needs further study.
(2) there is no statistical difference in the effect of CTX on different pathological types of thymoma. It is suggested that the pathological classification of thymoma may not be related to the therapeutic effect of CTX. However, because of the small sample size, short observation time, the difference of CTX effect may not be revealed, and it needs to increase the sample size and prolonged observation time.
(3) after CTX treatment, the attenuation of low frequency amplitude of RNS decreased and was consistent with the improvement of clinical absolute score of myasthenia gravis, so it could be used as a monitoring index for the therapeutic effect of CTX in the treatment of myasthenia gravis and thymoma.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R736.3;R746.1

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