ESHAP方案治疗难治性或复发性恶性淋巴瘤的疗效观察

目的：探讨ESHAP方案对难治性或复发性恶性淋巴瘤(Malignant lymphoma，ML)的疗效。方法：采用ESHAP方案治疗36例难治性或复发性恶性淋巴瘤，其中难治性非霍奇金淋巴瘤(NHL)17例，复发NHL16例，难治性或复发性霍奇金淋巴瘤(HL)3例。结果：12例难治性或复发性ML患者达完全缓解(CR率为33．3％)，10例达部分缓解(PR率为27．8％)；总有效率为61．1％，其中生存最长者43个月，仍处于CR期。毒副作用主要为消化道症状、轻度肝功能异常以及骨髓抑制。结论：ESHAP方案对部分难治性或复发性ML患者仍有效，毒副作用可以耐受。可用于治疗对其他化疗方案无效的难治性或复发性ML。     

GDP节拍方案对老年复发性及难治性非霍奇金淋巴瘤的临床效果分析

目的 探讨吉西他滨、地塞米松联合顺铂（GDP）节拍化疗方案对老年复发性及难治性非霍奇金淋巴瘤（NHL）的临床效果及不良反应。方法 选择2012年1月至2015年1月西安市中心医院血液科收治的老年复发性及难治性NHL患者18例，明确诊断后采用GDP节拍化疗方案进行治疗，治疗后对临床疗效、不良反应进行评估。结果 B细胞NHL患者中完全缓解（CR）3例、部分缓解（PR）2例，T细胞NHL患者CR 3例、PR 1例，总有效率（ORR）为50%，治疗过程中无治疗相关死亡。根据WHO制定的化疗药物毒副反应评价标准，患者治疗后主要不良反应主要集中在0～Ⅰ级，Ⅳ级并未发生，肝肾毒性轻微。发生不良反应主要为骨髓抑制及胃肠道反应，未发生明显的神经毒性及心脏毒性。结论 GDP节拍化疗方案是治疗老年复发性及难治性NHL的有效方案，具有更低的化疗毒副作用的发生，值得进一步推广。     

伊立替康联合米托恩醌治疗难治／复发性非霍奇金淋巴瘤的疗效观察

目的：在国内首次报道伊立替康（开普拓）联合米托恩醌治疗难治和复发非霍奇金淋巴瘤（NHL）的疗效;为难治性NHL的治疗寻找新的方法。方法：采用开普拓联合米托恩醌为主的化疗方案治疗21例难治和复发NHL,评价其疗效及不良反应。结果：7例（33．3％）难治和复发NHL达完全缓解（CR）;8例（38．1％）达部分缓解（PR）;总有效率为71．4％。不良反应主要为骨髓抑制、迟发性腹泻以及胃肠道反应,患者均能耐受。结论：开普拓联合米蒽醌对NHL特别是部分难治和复发NHL仍有效,不良反应可以耐受。可用于治疗对其他化疗方案无效的难治和复发NHL。     

阿米福汀联合ICE方案治疗老年复发性非霍奇金淋巴瘤疗效观察

目的:评价阿米福汀联合ICE方案治疗老年复发性非霍奇金淋巴瘤(NHL)的临床疗效和不良反应。方法:44例老年复发性NHL患者分为ICE治疗组(21例)及阿米福汀联合ICE治疗组(23例),观察2组临床疗效和不良反应。结果:阿米福汀-ICE组23例共接受92个疗程,10例完全缓解(CR),5例部分缓解(PR),总有效率(0R)65．2％。ICE组21例共接受84个疗程,7例CR,4例PR,OR 52．3％。2组主要治疗相关的不良反应为骨髓抑制,阿米福汀-ICE组重度白细胞减少和血小板减少发生率分别为13．0％和26．1％,明显低于ICE组(28．6％和42．9％),2组比较差异有统计学意义(P<0．05)。结论:阿米福汀联合ICE方案是治疗老年复发性NHL的有效挽救方案,其中阿米福汀能明显改善化疗相关的骨髓抑制而不影响其疗效。     

立体定向放射治疗配合化疗治疗非小细胞肺癌

目的观察立体定向放射治疗配合化疗治疗非小细胞肺癌的近期疗效。方法31例非小细胞肺癌患者均行NP方案(N：去甲长春花碱25mg／m^2第1．8天给予；P:顺铂60-80mg／m^2分2-3d给予；21d为1个周期)化疗加立体定向同步治疗。结果31例全部完成治疗计划，肺原发灶完全缓解(CR)占19．3％，部分缓解(PR)占74、2％，无变化和进展(NR PD)占6．5％，总有效(CR PR)率93．5％；纵隔淋巴结完全缓解(CR)占34、2％，部分缓解率为65．8％，无变化和进展(NR PR)占0％，总有效率(CR PR)为100％，白细胞下降率为96．8％，其中3．4级白细胞下降45.2％，放射性食管炎和放射性肺炎的发生率分别为54．8％和12．9％，均为1、2级。结论立体定向放射治疗配合化疗治疗非小细胞肺癌有较好的近期疗效。     

阿糖胞苷联合米托蒽醌治疗难治性白血病

目的：寻找复发性及难治性白血病有效治疗方案。方法：选用中剂量阿糖胞苷联合米托蒽醌治疗复发及难治性白血病16例。结果：显示完全缓解率83．3％，部分缓解率5.6％，总有效率为88.9％，主要毒副反应为骨髓抑制，全血象减少导致发生感染及出血。结论：本方案是治疗复发及难治性白血病的有效方案，加强支持治疗是保证疗效的关键。     

自体外周血干细胞移植治疗复发或难治性非霍奇金淋巴瘤5例

非霍奇金淋巴瘤(NHL)是一种常见的血液系统恶性肿瘤,可危及人类生命,尽管目前对NHL的治疗取得了一定的进展,生存期取得了一定延长,但仍有一部分患者对一线化疗药物不敏感。经2个疗程化疗无效者称为难治性病例[1],而且已经获得完全缓解(CR)的患者仍有半数最终复发,复发后常规化疗常难于缓解,所以难治性及复发性非霍奇金淋巴瘤的治疗成为淋巴瘤治疗的一大难题。为了解决这个难题,我科自2002年先后对5例难治或复发性NHL患者行自体外周血干细胞移植(Auto-PB SCT,简称“移植”),采用大剂量阿糖胞苷加米托蒽醌及粒细胞集落刺激因子(G-CSF…     

立体定向适形放疗和肝动脉插管化疗栓塞治疗原发性肝癌

目的 探讨立体定向适形放疗及肝动脉插管化疗栓塞(TAC／TAE)对原发性肝癌的疗效。方法 应用WDXK-808立体定向放疗系统、WDVE-6／100直线加速器，DT量3600CGY／6S／zw，立体定向适形放疗1周后行TAC／TAE。用药为5-FU1000mg，阿霉素40mg，丝裂霉素C10mg，IL-2200万单位。然后观察毒副作用、疗效和生存率。结果 18例原发性肝癌治疗后复查：CR27.8％(5／8)，PR44．4％(8／18)，总有效率(CR PR)为72.2％(13／18)。NC16．7％(3／18)。PD11．1％(2／18)。甲胎蛋白(AFP)下降率为88．8％(16／18)，1年生存率为61．1％(11/18)，2年生存率为38．8％(7／18)。局部控制率1年为55．5％(10/18)，2年为33．3％(6／18)。结论 立体定向适形放疗及TAC／TAE联合应用是治疗中晚期原发性肝癌有效的方法。     

时辰高剂量化疗联合白体骨髓移植治疗非霍奇金淋巴瘤的长期随访

目的 探讨在自体骨髓(造血干细胞)移植技术支持下应用时辰高剂量的环磷酰胺、足叶乙甙、阿糖胞苷和表阿霉素等组成COAE预处理化疗方案治疗预后差的中高度恶性非霍奇金淋巴瘤(NHL)的疗效。方法 观察11例NHL患者应用该项治疗后造血与免疫功能重建、长期无病生存率、毒副作用及移植相关死亡等．选用C0X回归模型分析性别、年龄、预处理方案、分期、移植时状态等对无病生存时间的影响。结果 所有患者均获得造血与免疫功能重建。随访1、3、5年，无病生存率分别为81．8％、63．6％、54．5％．最长存活9年。5例复发(45．4％)。无移植相关死亡。结论 该法在给药时间上进行了创新，提高了疗效，减低了高剂量化疗的毒副作用。该法作为有不良预后因素的中高度恶性NHL患者诱导化疗达完全缓解后强化治疗手段的远期疗效显著，优于常规化疗，能够改善生存率。     

以氟达拉滨为主的联合化疗方案治疗初治慢性淋巴细胞白血病临床分析

目的：评价以氟达拉滨为主的联合化疗方案治疗初治慢性淋巴细胞白血病（CLL）的疗效，并观察其不良反应。方法：患者为初治CLL。患者的治疗采用单药氟达拉滨（F）或氟达拉滨加环磷酰胺（FC）方案。结果：CLL患者27例，中位年龄57（41～66）岁，男19例，女8例。14例完全缓解（CR），CR率为51．85％；总有效率（OR）为85．19％。单用F11例，CR率36．36％；FC方案16例，CR率62．5％，2组CR率比较差异无统计学意义（P〉0．05）。0和Ⅰ期患者17例，CR率为70．59％；Ⅱ～Ⅳ期患者10例，CR率为20％；2者比较差异有统计学意义（P〈0．05）。23例有效患者随访PFS，中位随访时间为14个月（2～32个月）。中位疾病无进展生存时间（PFS）未达到。结论：以F为基础的方案可以作为CLL的一线治疗方案。FC可能应作为CLL一线治疗的首选方案，特别是对Rai分期0或Ⅰ期患者。     

Mitoxantrone, etoposide, cisplatin and dexamethasone (MEPD) as salvage chemotherapy in resistant non-Hodgkin's lymphoma

BACKGROUND. An effective second-line treatment for intermediate and high grade non-Hodgkin's lymphoma is greatly needed since 30% of patients do not achieved complete remission (CR) and another 20% to 30% of the CRs will eventually relapse. METHODS. A four-drug combination with Mitoxantrone, Etoposide, Cisplatin and Dexamethasone (MEPD) was devised for the treatment of patients with relapsing or refractory non-Hodgkin's lymphoma (NHL). So far 22 patients with intermediate or high grade NHL have entered the study. All patients were previously treated with doxorubicin based regimens. RESULTS. Seven patients obtained a complete remission (CR), 3 a partial remission (PR), 4 a minor response (MR) and 8 were treatment failures (F). Thus, an overall response rate of 45% has been achieved. To date three of the complete responders have relapsed at 3, 6 and 15 months. Four patients are still in CR at +2, +4, +9 and +17 months, respectively. Patients with relapsing lymphoma responded better than those with primary refractory disease. Myelosuppression was the most frequent side effect, nevertheless there were no severe infections. CONCLUSIONS. These preliminary results suggest the effectiveness of MEPD as salvage chemotherapy in resistant NHL and warrant further clinical studies.     

Busulfan, cyclophosphamide, and etoposide as high-dose conditioning regimen in patients with malignant lymphoma

We investigated the efficacy and toxicity of the combination of busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16) as a preparative regimen prior to autologous hematopoietic stem cell transplantation (ASCT) in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). Fifty-three patients with recurrent ( n=30), refractory ( n=20), or high-risk ( n=3) lymphoma were enrolled. The 10 patients with HD and 43 with NHL (median age: 46 years, range: 18-64) received busulfan (16 mg/kg), cyclophosphamide (120 mg/kg), and etoposide (30 or 45 mg/kg) followed by ASCT. A total of 50 patients (94%) were consolidated in complete ( n=25) or partial ( n=25) remission, whereas 3 patients had chemoresistant disease before Bu/Cy/VP-16. Thirty-five patients (66%) had received prior radiotherapy (RT) excluding total body irradiation (TBI) as part of the conditioning regimen. The main nonhematological toxicities (grade II-IV according to the Bearman score) in 52 evaluable patients were mucositis (79%) and hepatic toxicity (15%). Severe veno-occlusive disease (VOD) occurred in three patients (5.8%) including one treatment-related death caused by VOD. Overall, treatment-related mortality was 3.8%. After a median follow-up for surviving patients of 21 months (range: 6-118), 20 patients (38%) are in continuous complete remission, 8 patients (15%) are alive in relapse, and 25 patients (47%) died. Probabilities of relapse, event-free survival, and overall survival at 3 years were 63% [95% confidence interval (CI): 48-79%], 31% (95% CI: 17-46%), and 43% (95% CI: 27-59%), respectively. In conclusion, Bu/Cy/VP-16 is an effective and well-tolerated conditioning regimen in patients with HD and NHL. Both toxicity and outcome were not significantly different in patients treated with 30 mg/kg and 45 mg/kg etoposide, respectively. The observed long-term results are even comparable to those published for other established high-dose protocols, including TBI-based regimens. However, further investigations are necessary to evaluate the value of Bu/Cy/VP-16 as a high-dose protocol for malignant lymphoma, especially in patients who have already received extensive RT.     

Alternating mini-BEAM/ESHAP as salvage therapy for refractory non-Hodgkin's lymphomas

 Mini-BEAM and ESHAP are two non-cross-resistant salvage regimens that have been used separately in patients with lymphoma. The aim of the present study was to investigate the efficacy of the combination of these two regimens, administered in alternating cycles, as salvage therapy for refractory non-Hodgkin's lymphoma (NHL) patients. A total of 28 patients were included in the study: 14 patients were primary refractory, seven were partial responders, and seven were in relapse. The alternating cycles of mini-BEAM and ESHAP were given until there was maximum response or progression. The overall response rate to mini-BEAM/ESHAP was 39%; 25% of patients achieved a complete response and 14% a partial response. Nevertheless, it should be noted that none of the primary refractory patients responded to this protocol. Nine of the 11 patients who responded to mini-BEAM/ESHAP were consolidated with autologous transplantation using BEAM as a conditioning regimen. The survival at 3 years in this group of 11 patients who responded to the salvage regimen is 64%, with a disease-free survival of 67% at 2 years. No major toxic effects were observed with mini-BEAM/ESHAP. Myelosuppression was the most frequent complication, especially with the mini-BEAM cycles. Other toxicities were infrequent and no treatment-related deaths were observed. These results suggest that alternating mini-BEAM/ESHAP chemotherapy is a safe regimen that is effective in partial responders or relapsing patients with NHL who have sensitive disease, but not in primary refractory patients. Moreover, although this therapy has a potential advantage, combining as it does two non-cross-resistant regimens, it does not seem superior to ESHAP alone. Received: 16 July 1996 / Accepted: 31 October 1996     

Mobilization of peripheral blood stem cells with high-dose cyclophosphamide or the DHAP regimen plus G-CSF in non-Hodgkin's lymphoma

Our study analyzes the mobilization of hematopoietic stem cells after two chemotherapeutic regimens in non-Hodgkin's lymphoma (NHL) patients. The study included 72 patients with NHL (42 follicular and 30 large cells). The mean age was 37 years (range 17-60). Sixty-four patients (88.9%) had stage III-IV disease. Forty-eight patients (66.7%) had bone marrow involvement. Systemic B symptoms were present in 42 patients (58.3%). Mobilization chemotherapy regimens were randomly assigned as DHAP in 38 patients (52.7%) or cyclophosphamide (CPM) (5 g/m(2)) in 34 (47.2%) and the results of 132 procedures were analyzed. At the time of PBSC mobilization, 46 patients (63.9%) were considered to be responsive (complete remission, partial remission or sensitive relapse) and 26 (36.1%) not responsive (refractory relapse or refractory to therapy). Pre-apheresis CD34+ blood cell count and number of previous chemotherapy treatments were used to predict the total number of CD34+ cells in the apheresis product. The mobilizing regimens (CPM or DHAP) were similar in achieving the threshold CD34+ cell yield, for optimal engraftment. Since DHAP was very effective as salvage treatment, we suggest using DHAP as a mobilizing regimen in patients with active residual lymphoma at the time of stem cell collection.     

Ifosfamide,epirubicin and etoposide regimen as salvage and mobilizing therapy for relapsed/refractory lymphoma patients

BACKGROUND AND OBJECTIVES: Therapy for relapsed/refractory lymphomas should be based only on drugs not included in the front-line chemotherapy regimens. We adopted the strategy of using salvage chemotherapy to debulk disease and simultaneously mobilize stem cells, using a regimen based on ifosfamide and etoposide, (drugs not usually used for front-line treatment). DESIGN AND METHODS: A three-drug combination of ifosfamide, epirubicin and etoposide (IEV) was used to treat 62 patients with relapsing or refractory aggressive non-Hodgkin's lymphoma (NHL; n=51) or Hodgkin's disease (HD; n=11). Forty-five of the patients were studied for the feasibility of peripheral blood stem cell (PBSC) harvest. RESULTS: The overall and complete response (CR) rates were, respectively, 77% and 32% in the NHL subset and 81% and 45% in the HD subset. Among the 17 patients who achieved CR after IEV but did not have a subsequent transplantation, the median duration of the response was 9 months (range, 2 to 14 months). Mobilization was successful in 33 of 45 (71%) patients. Among the 45 who proceeded to autotransplantation, 27 (60%) were in CR status after the autograft; 23/45 (51%) patients are currently in continuous CR with a median follow-up of 25 months (range, 10-68 months); the relapse-free survival curve shows 83% in this state at 60 months. Twenty-three (37%) patients are currently in continuous CR with a median follow-up of 25 months. Clinical and hematologic toxic effects were mild. INTERPRETATION AND CONCLUSIONS: Our results indicate the efficacy of the IEV regimen in inducing a good remission rate. IEV is a predictable and highly effective mobilization regimen in relapsed/refractory patients with aggressive NHL or HD.     

Efficacy of vinorelbine, epirubicin and prednisone combination regimen in pretreated elderly patients with aggressive non-Hodgkin's lymphoma

BACKGROUND AND OBJECTIVES: To assess the efficacy and toxic profile of the NAEPP protocol, a regimen including vinorelbine, epirubicin and prednisone, in a particularly troublesome subset of patients: pretreated elderly patients with aggressive non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: From November 1998 to January 2000, 20 pretreated patients who had all relapsed after first-line VNCOP-B chemotherapy were enrolled in a phase II trial and treated with the NAEPP regimen: vinorelbine (25 mg/m(2) i.v. on days 1 and 8), epirubicin (40 mg/m(2) i.v. on days 1 and 8), and prednisone (40 mg/m(2) on days 1 and 8) with granulocyte colony-stimulating factor administered at 5 mg/kg/day on days 2-5 and days 9-12. Chemotherapy was repeated every 4 weeks for a total of 6 cycles. RESULTS: Six (30%) patients achieved complete remission (CR) and 7 (35%) had partial responses (PR), giving an overall response rate of 65%. The response rate was not affected either by type of relapse presentation (nodal versus nodal plus extranodal), presence of bulky disease, or time of relapse. No major toxic effects were recorded. INTERPRETATION AND CONCLUSIONS: These preliminary data suggest that the NAEPP regimen is an effective combination with a low toxicity profile in elderly pretreated patients with aggressive NHL. Further trials using NAEPP as a consolidation phase following first-line treatment are needed to establish the advantage in terms of CR rate and relapse-free survival in these patients.     

Equitoxicity of bolus and infusional etoposide: results of a multicenter randomised trial of the German High-Grade Non-Hodgkins Lymphoma Study Group (DSHNHL) in elderly patients with refractory or relapsing aggressive non-Hodgkin lymphoma using the CEMP regimen (cisplatinum, etoposide, mitoxantrone and prednisone)

To compare toxicity of etoposide bolus with continuous infusion and to assess the efficacy of the CEMP (cisplatinum, etoposide, mitoxantrone, prednisone) regimen, 47 patients with refractory or relapsed aggressive non-Hodgkin's lymphoma older than 60 years (n=43) or not qualifying for high-dose chemotherapy (n=4) received five four-weekly CEMP cycles. Patients were randomised to start with bolus or continuous-infusion etoposide and then received bolus and infusional etoposide in an alternating fashion. The primary objective was the comparison of differences in the course of leukocytopenia and thrombocytopenia between the two application schedules. CEMP was well tolerated with little organ and moderate haematotoxicity. There was no difference in toxicity between bolus and continuous-infusion etoposide. Complete remission rate was 44% in patients relapsing >or=1 year, 27% in patients relapsing within the first year after achieving complete remission and 5% in primary refractory patients. Median event-free and overall survivals for all patients were 3 and 10 months, respectively. The observed equitoxicity and the more challenging logistics of a 60-h infusion make bolus injection the preferred application of etoposide. As the CEMP regimen is well tolerated and efficacious in elderly patients with relapsed or refractory aggressive non-Hodgkin's lymphoma for whom more aggressive therapies are not feasible, a three-weekly modification of CEMP should be tested in combination with rituximab.     

High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation in patients with lymphoma -- a retrospective evaluation

The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thiotepa, melphalan, and carboplatin (TMCb), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 42 patients, 23 with intermediate-grade NHL and 19 with HD, received thiotepa (500 mg/m2), melphalan (100 mg/m2), and carboplatin (1050-1350 mg/m2) followed by autologous PBSC infusion. Of 21 patients with more advanced disease, four had primary refractory disease, one was in complete remission (CR)-2, 11 were in first refractory relapse, and five were beyond first relapse. Of 21 patients with less advanced disease, two were in CR-1, four were in CR-2, and 15 were in first responding relapse. In all, 14 patients (33%) had received prior radiotherapy prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival (EFS), and relapse for all patients were 0.65, 0.60, and 0.21 (0.85, 0.80, and 0.10 for patients with less advanced disease and 0.47, 0.42, and 0.33 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.12. Grade 3-4 regimen-related toxicities (RRT) occurred in five of 42 (12%) patients and death due to grade-4 RRT occurred in only one (2.5%) patient. These preliminary data suggest that 0.42% EFS in this study for advanced disease patients is highly encouraging and high-dose TMCb followed by autologous PBSC transplantation is well tolerated as well as an effective regimen in patients with intermediate-grade NHL or HD, and may be comparable to some previously used regimens including TBI-based regimens.     

Ifosfamide,mitoxantrone and etoposide (VIM) as salvage therapy of low toxicity in non-Hodgkin's lymphoma

Abstract: Patients with non-Hodgkin's lymphoma (NHL) who fail to respond to first-line treatment or relapse after having shown complete or partial remission have a poor prognosis, especially in high-grade NHL. Several salvage regimens show considerable toxicity and a poor long-term outcome. In this retrospective study we analyzed data of 55 patients (34 men and 21 women) with a median age of 66 years (range: 18–89). The combination chemotherapy (VIM) consisted of VP-16 (etoposide) 65 mg/m², ifosfamide 650 mg/m² and mitoxantrone 3 mg/m² and was administered on 3 consecutive days along with mesna as uroprotection. Patients were treated for refractory disease or relapse and did not qualify for high-dose chemotherapy and ABMT. Stages according to the An Arbor classification were: stage I/16, II/4, III/8 and IV/37 patients. Thirty-three patients suffered from high-grade and 22 from low-grade NHL. Toxicity (WHO recommendations) was very mild. High-grade NHL showed a better response rate (18/33, 46%) than low-grade NHL (7/22, 36%). Overall response was 41% (12 CR and 11 PR) with a median duration of 36 months (range: 6–57 months). The combination therapy investigated exhibits mild toxicity even in extensively pretreated or elderly patients. The overall response rate of 41% might be improved by increased dosage and growth factor support.