【作者】 赵亮；

【导师】 黄湘华； 刘志红；

【作者基本信息】 南京大学 ， 内科学， 2017， 硕士

【摘要】 目的:系统性轻链型淀粉样变性(systemic immunoglobulin light chain amyloidosis,AL)是临床上最常见,也是预后最差的一种淀粉样变性。化疗和自体干细胞移植是该病的主要治疗手段,国外小样本研究表明沙利度胺联合地塞米松(thalidomide combined dexamethasone,TD)化疗方案对复发和难治性AL患者有一定的疗效,但国内外尚缺乏TD方案对初治AL患者的疗效和毒副反应的报道。本研究旨在通过回顾性分析AL患者的临床和预后资料,探讨TD方案对初治AL的疗效和安全性。方法:回顾性分析2009年4月至2014年12月在南京总医院确诊并采用TD方案作为初治方案的63例AL型淀粉样变性患者的临床及随访资料。所有患者均采用TD方案治疗4个疗程及以上,沙利度胺起始治疗剂量为50mg/晚,1周后未见不良反应则加量至100mg/晚,以此类推,最高剂量为200mg/晚,地塞米松起始治疗剂量为40mg/周,28天为1个治疗周期。应用Kaplan-Meier法计算患者生存时间,组间对比采用log-rank检验,利用COX风险比例模型分析预后危险因素。结果:本研究共纳入患者63例,男女比例为1.52:1,中位年龄为57岁,中位治疗周期为19个(4-78个)。38例患者(60.3%)心脏受累,38例患者(60.3%)两个或以上的器官受累。37例患者取得血液学缓解,总体血液学缓解率为58.7%,中位到达缓解的时间为4个月,其中18例患者(28.5%)达到完全缓解(complete response,CR),中位到达缓解的时间为3个月,10例患者(15.9%)达到非常好的部分缓解(very good partial response,VGPR),中位到达缓解的时间为5.5个月,9例患者(14.2%)达到部分缓解(partial response,PR),中位到达缓解的时间为5个月。23例患者(36.5%)获得器官缓解,肾脏缓解和心脏缓解分别为23例(36.5%)和10例(15.9%),中位到达缓解的时间分别为8.5和18.8个月。有3例患者病情复发,中位复发时间为7个月(3-19个月)。患者的中位随访时间为28个月,2年生存率为78.5%,K-M曲线估计的中位生存时间尚未达到。达到血液学缓解的患者相比未达到血液学缓解的患者预后更好(3年生存率87.5%vs.36.3%,P<0.01),心脏受累的患者相比无心脏受累的患者预后更差(3年生存率52.4%vs.87%,P<0.05)。常见不良反应包括外周神经病变(23.8%)、胃肠道反应(17.5%)、乏力(11/1%)、皮疹(6.3%)等。9例患者因不良反应和治疗无效停药,12例患者沙利度胺减量,22例患者地塞米松减量。结论:TD方案对初治的AL型淀粉样变性患者有一定的疗效,并具有较好的耐受性,可以作为不适合行大剂量马法兰联合自体外周血干细胞移植(high-dose melphalan/autologous peripheral blood stem cell transplantation,HDM/ASCT)及硼替佐米联合地塞米松(bortezomib combined dexamethasone,BD)方案化疗患者的备选方案,其长期疗效有待进一步观察。更多还原

【Abstract】 Objective:Systemic immunoglobulin light chain amyloidosis(AL)is the most common type of amyloidosis with the worst prognosis.Chemotherapy and autologous stem cell transplantation are the main therapies for the disease.Foreign small sample researches showed the regiment of thalidomide combined dexamethasone was effective for recurrent and refractory AL patients,but there is no study about the regiment of thalidomide combined dexamethasone showing the efficacy and adverse reactions for untreated AL patients.The article retrospectively analyzes the clinical and prognostic dates of AL patients to evaluate the efficiency and safety of the regiment of thalidomide combined with dexamethasone in untreated patients of systemic immunoglobulin light chain amyloidosis.Methodology:The clinical dates of 63 patients diagnosed AL amyloidosis here were retrospectively analyzed from April 2009 to December 2014,all the patients took the regiment of thalidomide combined with dexamethasone as the first line treatment,all the them took the regiment for 4 cycles at least.The initial dose of thalidomide was 50 mg every night with increment to 100 mg after one week if there was no adverse reaction,and the highest dose was 200mg every night,the initial dose of dexamethasone was 40mg every week,one cycle of the treatment was 28 days.Survival curves were constructed according to the Kaplan-Meier method.The relation of clinical factors to all-cause mortality was assessed using proportional hazards regression.Result:A total of the 63 patients were enrolled in this study,the rate of males and females were 1.51:l,median age was 57,the cycle of treatment for 63patients is 19(4-78),38 patients had heart involved,and 38 patients had two more organs involved.In total,37 patients(58.7%)achieve different hematological response,median time of response were 4 months,in which 18 patients(28.6%)achieve complete response,median time of response were 3 months,10 patients(15.9%)achieve very good partial response,median time of response were 5.5 months and 9 patients(14.3%)achieve partial response,median time of response were 5 months.There were 23 patients(35.9%)obtaining organ response,of which mainly were renal response,median time to organ response were 8.5 months,heart response were(15.9%),median time to organ response were 18.8 months.3 patients had a relapse,median time to relapse was 7 months(3-19months).The median follow-up period was 28 months,the survival rate at two years was 78.5%,and the median overall survival time did not reach.Compared to the non-hematological response group,the hematological response group has a better prognosis,prognosis of the heart involvement group is worse comparing to the non-heart involved group.Common adverse reaction was sensoryneuropathy(23.8%),digestive tract reaction(17.5%),asthenia(11.1%),rash(6.3%)and so on,without treatment related mortality.9 patients ended treatment for the adverse effects,dose of thalidomide was decreased in 12 patients,and dose of dexamethasone was decreased in 22 patients.Conclusion:The regiment of thalidomide combined with dexamethasone seems to be an effective and tolerant approach for the first line treatment of AL amyloidosis,it can be a candidate for patients were not suitable for high-dose melphalan/autologous peripheral blood stem cell transplantation or chemotherapy regiment of the bortezomib combined dexamethasone,and the long-term efficacy is still needed to be seen.更多还原