累积大剂量环磷酰胺治疗伴发胸腺瘤重症肌无力
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摘要
目的观察累积大剂量环磷酰胺(CTX)治疗伴胸腺瘤重症肌无力(MG)的有效性和安全性。方法对2006年5月至2018年5月本中心应用CTX治疗的伴胸腺瘤MG患者进行回顾性分析,选取输注药物总量≥30 g的患者为研究对象,记录MG临床相对评分、不良反应等。结果应用CTX达30 g后MG相对评分好转≥95%者11例,80%~95%者4例,50%~80%者2例,总有效率100%,总治愈率88.2%。治疗过程中,出现27例次药物不良反应,白细胞减少8例,丙氨酸氨基转移酶升高7例,恶心6例,疲乏1例,出汗增多1例,月经推迟1例,闭经1例,带状疱疹1例,高调耳鸣1例。结论应用CTX治疗伴发胸腺瘤MG,累积剂量达30 g时可获得显著疗效;白细胞减少、肝损害为主要不良反应,给予对症处理后可顺利完成治疗。
Objective To observe the efficacy and safety of accumulated high-dose cyclophosphamide(CTX)therapy in myasthenia gravis(MG)patients with thymoma. Methods Data from MG patients with thymoma who underwent CTX pulse therapy in our center from May 2006 to May 2018 were retrospectively reviewed. Patients whose cumulative CTX dose reached to 30 g or more were selected as objects. Clinical data,including clinical relative score and adverse effects of MG with thymoma,were recorded. Results The clinical relative scores declined more than 95% in 11 cases,80%~95% in 4 cases,50%~80% in 2 cases. The effective ratio was100%,and the curative ratio was 88.2%. Twenty-seven adverse events were documented. These side effects were leukopenia(n = 8),elevated alanine transaminase levels(n = 7),nausea(n = 6),fatigue(n = 1),increased sweating(n = 1),delayed menstruation(n = 1),amenorrhea(n = 1),herpes zoster(n = 1),and high pitch tinnitus(n = 1). Conclusions Intravenous pulse CTX is significantly effective in the treatment of MG patients with thymoma,when the total cumulative doses reached to 30 g. Leukopenia and liver damage were the common adverse reactions. When adverse events were managed symptomatically,the treatment could be completed successfully.
Objective To observe the efficacy and safety of accumulated high-dose cyclophosphamide(CTX)therapy in myasthenia gravis(MG)patients with thymoma. Methods Data from MG patients with thymoma who underwent CTX pulse therapy in our center from May 2006 to May 2018 were retrospectively reviewed. Patients whose cumulative CTX dose reached to 30 g or more were selected as objects. Clinical data,including clinical relative score and adverse effects of MG with thymoma,were recorded. Results The clinical relative scores declined more than 95% in 11 cases,80%~95% in 4 cases,50%~80% in 2 cases. The effective ratio was100%,and the curative ratio was 88.2%. Twenty-seven adverse events were documented. These side effects were leukopenia(n = 8),elevated alanine transaminase levels(n = 7),nausea(n = 6),fatigue(n = 1),increased sweating(n = 1),delayed menstruation(n = 1),amenorrhea(n = 1),herpes zoster(n = 1),and high pitch tinnitus(n = 1). Conclusions Intravenous pulse CTX is significantly effective in the treatment of MG patients with thymoma,when the total cumulative doses reached to 30 g. Leukopenia and liver damage were the common adverse reactions. When adverse events were managed symptomatically,the treatment could be completed successfully.
引文
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[8] JAISWAL S R,BHAKUNI P,ZAMAN S,et al. T cell costimulation blockade promotes transplantation tolerance in combination with sirolimus and post-transplantation cyclophosphamide for haploidentical transplantation in children with severe aplastic anemia[J]. Transpl Immunol,2017,43-44:54-59.
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[11]康慧琳,樊卫平,雷波,等.不同剂量环磷酰胺对小鼠免疫功能的影响[J].免疫学杂志,2018,34(4):308-312.
[12] PESTRONK A,DRACHMAN D B,ADAMS R N. Treatment of ongoing experimental myasthenia gravis with short term high dose cyclophosphamide[J]. Muscle Nerve,1982,5(1):79-84.
[13] DE FEO L G,SCHOTTLENDER J,MARTELLI N A,et al.Use of intravenous pulsed cyclophosphamide in severe,generalized myasthenia gravis[J]. Muscle Nerve,2002,26(1):31-36.
[14]黄玲,王磊,尹世敏,等.环磷酰胺治疗伴胸腺瘤的重症肌无力临床研究[J].中国现代神经疾病杂志,2014,14(10):878-882.
[15] PEREZ M C,BUOT W L,MERCADO-DANGUILAN C,et al.Stable remissions in myasthenia gravis[J]. Neurology,1981,31(1):32-37.
[16] AGHAIE S,NIKZAD H,MAHABADI J A,et al. Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics,biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide[J]. Anat Sci Int,2016,91(4):382-390.
[17] QI G,LIU P,DONG H,et al. Metastatic thymoma-associated myasthenia gravis:Favorable response to steroid pulse therapy plus immunosuppressive agent[J]. Med Sci Monit,2017,23:1217-1223.
[18] BARNES H,HOLLAND A E,WESTALL G P,et al. Cyclophosphamide for connective tissue disease-associated interstitial lung disease[J]. Cochrane Database Syst Rev, 2018, 1:CD010908.
[19] NAGAPPA M,NETRAVATHI M,TALY A B,et al. Long-term efficacy and limitations of cyclophosphamide in myasthenia gravis[J]. J Clin Neurosci,2014,21(11):1909-1914.
[20] BUZZARD K A,MEYER N J,HARDDY T A,et al. Induction intravenous cyclophosphamide followed by maintenance oral immunosuppression in refractory myasthenia gravis[J]. Muscle Nerve,2015,52(2):204-210.
[2]中华医学会神经病学分会神经免疫学组,中国免疫学会神经免疫学分会.中国重症肌无力诊断和治疗指南2015[J].中华神经科杂志,2015,48(11):934-940.
[3] SANDERS D B,WOLFE G I,BENATAR M,et al. International consensus guidance for management of myasthenia gravis:Executive summary[J]. Neurology,2016,87(4):419-425.
[4]许贤豪.神经免疫学[M].武汉:湖北科学技术出版社,2000:100-155.
[5] LIU G C,GAO B L,YANG H Q,et al. The clinical absolute and relative scoring system-a quantitative scale measuring myasthenia gravis severity and outcome used in the traditional Chinese medicine[J]. Complement Ther Med,2014,22(5):877-886.
[6] DRACHMAN D B,JONES R J,BRODSKY R,et al. Treatment of refractory myasthenia:“rebooting”with a high-dose cyclophosphamide[J]. Ann Neurol,2003,53(1):29-34.
[7]陈峋,苏海霞,覃远汉,等.环磷酰胺冲击治疗儿童难治性肾病的临床分析[J].实用医学杂志,2017,33(17):2907-2910.
[8] JAISWAL S R,BHAKUNI P,ZAMAN S,et al. T cell costimulation blockade promotes transplantation tolerance in combination with sirolimus and post-transplantation cyclophosphamide for haploidentical transplantation in children with severe aplastic anemia[J]. Transpl Immunol,2017,43-44:54-59.
[9] MEHRA S,USDADIYA J B,JAIN V K,et al. Comparing the efficacy of low-dose vs high-dose cyclophosphamide regimen as induction therapy in the treatment of proliferative lupus nephritis:A single center study[J]. Rheumatol Int,2018,38(4):557-568.
[10] HIJIKATA Y,OKAZAKI T,TANAKA Y,et al. A phase I clinical trial of RNF43 peptide-related immune cell therapy combined with low-dose cyclophosphamide in patients with advanced solid tumors[J].PLoS One,2018,13(1):e0187878.
[11]康慧琳,樊卫平,雷波,等.不同剂量环磷酰胺对小鼠免疫功能的影响[J].免疫学杂志,2018,34(4):308-312.
[12] PESTRONK A,DRACHMAN D B,ADAMS R N. Treatment of ongoing experimental myasthenia gravis with short term high dose cyclophosphamide[J]. Muscle Nerve,1982,5(1):79-84.
[13] DE FEO L G,SCHOTTLENDER J,MARTELLI N A,et al.Use of intravenous pulsed cyclophosphamide in severe,generalized myasthenia gravis[J]. Muscle Nerve,2002,26(1):31-36.
[14]黄玲,王磊,尹世敏,等.环磷酰胺治疗伴胸腺瘤的重症肌无力临床研究[J].中国现代神经疾病杂志,2014,14(10):878-882.
[15] PEREZ M C,BUOT W L,MERCADO-DANGUILAN C,et al.Stable remissions in myasthenia gravis[J]. Neurology,1981,31(1):32-37.
[16] AGHAIE S,NIKZAD H,MAHABADI J A,et al. Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics,biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide[J]. Anat Sci Int,2016,91(4):382-390.
[17] QI G,LIU P,DONG H,et al. Metastatic thymoma-associated myasthenia gravis:Favorable response to steroid pulse therapy plus immunosuppressive agent[J]. Med Sci Monit,2017,23:1217-1223.
[18] BARNES H,HOLLAND A E,WESTALL G P,et al. Cyclophosphamide for connective tissue disease-associated interstitial lung disease[J]. Cochrane Database Syst Rev, 2018, 1:CD010908.
[19] NAGAPPA M,NETRAVATHI M,TALY A B,et al. Long-term efficacy and limitations of cyclophosphamide in myasthenia gravis[J]. J Clin Neurosci,2014,21(11):1909-1914.
[20] BUZZARD K A,MEYER N J,HARDDY T A,et al. Induction intravenous cyclophosphamide followed by maintenance oral immunosuppression in refractory myasthenia gravis[J]. Muscle Nerve,2015,52(2):204-210.