增加疗程的强化改良化疗方案治疗非霍奇金淋巴瘤的临床研究

Clinical Study of Non Hodgkin's Lymphoma Treated with Enhanced Chemotherapy Regimen and Increased Treatment Courses

目的:总结和研究增加疗程的强化改良化疗方案治疗非霍奇金淋巴瘤(Non-Hodgkin's lymphoma,NHL)的疗程数、近期疗效、远期生存和安全性,为提高NHL临床疗效提供新的治疗方案。方法:对西安交通大学第二附属医院2004年1月-2014年2月收治的NHL 254例患者采用多种强化密集的改良方案化疗,以改良CHOPE、MAED、MMED、TAED方案为主。全组患者分别接受了1-20个疗程化疗,平均中位疗程为14个,第1年中位疗程为8个(1-10个);第2年为4个(0-6个);第3年为2个(0-5个)。结果:1全组完全缓解率(CR)182例(71.7%),部分缓解率(PR)30例(11.8%),疾病稳定(SD)22例(8.7%),疾病进展(PD)20例(7.9%),总有效率(RR)212例(83.5%)。中位随访期为56.5个月,1、3、5年总存活率(OS)分别为90.1%、74.5%、61.1%,中位生存期为69个月,无疾病存活率(DFS)分别为81.8%、65.4%、54.7%,中位无病生存期为65个月。2早期的疗效中,获得CR、PR、SD、PD的3年OS分别为92.2%、56.0%、20.2%、0%;获得CR所需要的疗程数≤4个、>4个疗程的5年OS分别为83.1%、6.8%,DFS分别为72.4%、0%。3总疗程数<6个、6-8个、9-10个、11-13个、14个、15个、20个的复发率分别为82.5%、78.9%、71.9%、65.8%、41.8%、30.4%、16.7%;传统的6-8个疗程CHOP或CHOP类方案治疗患者中RR最高达50%-60%,复发率大于70%。结论:强化、密集的改良化疗方案治疗NHL相对于传统CHOP化疗方案,患者能尽快取得CR,显著提高NHL的治疗有效率、远期生存率,而且患者耐受性好。化疗强度是关系疗效的重要因素。在患者能耐受的情况下,适当增加NHL化疗疗程数(不少于14个),至少第1治疗年8个,第2年4个,第3年2个,能显著减低复发率,改善患者的远期预后。增加化疗疗程是减少复发的另一重要因素,值得进一步临床研究。

Objective:To study the non-Hodgkin's lymphoma treated with enhanced chemotherapy regimen and increase of treatment courses,including number of treatment courses,short-term efficacy,long-term survival and safety.Methods:All the 254 cases of NHL in our hospital from January 2004 to February 2014 received a variety of intensive enhanced chemotherapy regimen,such as CHOPE,MAED,MMED and TAED.The median number of treatment course was 14,including 8 in the 1st year,4 in the 2nd and 2 in the 3rd.Results:(1) In 254 assessable patients,182 patients(71.7%) achieved complete responses(CR),30 patients(11.8%) achieved partial responses(PR),22 patients(8.7%) achieved stable disease(SD),20 patients(7.9%) achieved progressive disease(PD),212 patients(83.5%)achieved response rate(RR).The median time of following-up was 56.5 months,the overall survivals(OS) of 1,3 and5 years were 90.1%,74.5%and 61.1%respectively,the median survival time was 69 months,and the disease-free survivals(DFS) were 81.8%,65.4%and 54.7%respectively,the median DFS was 65 months.(2) In therapeutic effects at early phase,the 3-year OS of patients who achieved CR,PR,SD and PD were 92.2%,56.0%,20.2%and0%respectively;The 5-year OS of patients who achieved CR through ≤4 cycle treatments and the 5-year OS of patients who achieved CR through >4 cycles treatments were 83.1%and 6.8%,their DFS were 72.4%and 0%respectively.(3) The relapse rates of patients who received < 6,6-8,9-10,11-13,14,15 and 20 cycle treatments were 82.5%,78.9%,71.9%,65.8%,41.8%,30.4%and 16.7%.The response rate(RR) of patients who received 6-8traditional chemotherapy cycle as CHOP or CHOP-like regimen were 50%-60%and relapse rate >70%.Conclusion:Compared with traditional chemotherapy regimens,the dose-escalated,intensive and modified chemotherapy regimen can significatly improve the therapeutic efficiency for patients with NHL,including CR,long-term survival rate,and a good tolerance for patients.The chemotherapy intensity has been confirmed to be an important factor that associated with therapeutic efficiency.On the conditions tolerated by patients,the number of treatment cycles for NHL patients can be increased at lest 14,with 8 in the first year,4 in the second year and 2 in the third year.The increase of chemotherapy cycle can obviously reduce the relapse rate and improve the long-term prognosis of patients.It is worth to further explore.