IEP方案治疗37例复发性、难治性非霍奇金淋巴瘤

[目的]研究复发性，难治性中高度恶性非零奇金淋巴瘤的解救治疗。[方法]37例复发性，难治性中高度恶性非霍奇金淋巴瘤病人用IEP方案治疗；异环磷酰胺（IFO）2g静脉点滴，第1-4天（同时使用美斯纳）；足叶乙甙（Vp-16)100mg，静脉点滴，第1-4天；顺铂30mg/m^2，静脉点滴，第1-3天；21-28天为1周期，连用2周期评定疗效。[结果]总缓解率为81.1%(30/37)。完全缓解率（CR）为35.1%(13/37)，部分缓解率为45.9%(17/37)。主要不良反应为骨髓抑制和脱发，白细胞减少发生率为83.8%，其中Ⅲ-Ⅳ度发生率占43.2%。血红蛋白及血小板减少发生率分别为37.8%和43.2%。脱发发生率为91.2%，其它不良反应湛和见。[结论]IEP方案可作为复发性，难治性中高度恶性淋巴瘤的解救治疗。     

ESHAP方案治疗复发性或难治性非霍奇金淋巴瘤的临床观察

目的:观察ESHAP方案治疗难治性或复发性非霍奇金淋巴瘤(NHL)的疗效及不良反应.方法:采用足叶乙甙、甲基强的松、顺铂、阿糖胞苷联合治疗20例NHL观察其治疗及不良反应.结果:20例中,完全缓解(CR)5例,部分缓解(PR)10例,总有效率(RR)75%.难治性6例中CR 1例,PR 3例,RR 67%.复发性14例中CR 4例,PR 7例,RR 79%.ESHAP方案的主要不良反应为骨髓抑制,白细胞减少的发生率为100%,Ⅲ-Ⅳ度为55%,血红蛋白及血小板减少的发生率分别为35%和55%,胃肠道反应发生率为45%,脱发发生率为55%,患者均可耐受.结论:ESHAP方案治疗复发性或难治性NHL是一种较理想的治疗方案.     

GOX 方案与DICE方案二线治疗非霍奇金淋巴瘤的临床对比研究

目的:对比奥沙利铂联合吉西他滨（GOX）与DICE方案二线治疗复发性或难治性非霍奇金淋巴瘤（NHL ）的疗效及毒副作用。方法:选取复发难治性非霍奇金淋巴瘤患者55例,随机分为两组,分别接受GOX方案和DICE方案化疗。GOX组方案为:GEM1 000mg/m2,静脉滴注,d1、d8,LOHP 130mg/m2,静脉滴注,d1;21d 为1 个周期。DICE组方案为: 地塞米松（DXM）20mg,静脉滴注,d1～d4;异环磷酰胺（IFO ）1g/m2,静脉滴注,d1～d4;Mesna解救400mg,静脉滴注q8h,d1～d4;顺铂（DDP ）25mg/m2,静脉滴注,d1～d4;依托泊苷（Vp- 16）100mg/m2,静脉滴注,d1～d4。21～28d 为1 个周期。每2 周进行疗效及毒性评价。结果:55例患者中,GOX方案组CR3 例（11.5%）,PR14例（53.8%）,SD5 例,PD4 例,总有效率（CR+PR）为65.4% ,临床获益率（CR+PR+SD ）达到84.6% 。DICE组CR4 例（13.8%）,PR12例（41.4%）,SD8 例,PD5 例,总有效率55.2% ,临床获益率82.7% 。针对不同的细胞类型,GOX组中T 细胞淋巴瘤患者总有效率为60.0% ,B 细胞淋巴瘤总有效率达68.8% ,在DICE组T 细胞淋巴瘤总有效率50.0% ,而B 细胞淋巴瘤为57.9% 。两组的毒副反应主要为骨髓抑制,其中GOX组白细胞下降Ⅲ度7 例,Ⅳ度2 例;贫血Ⅲ度2 例;血小板下降Ⅲ度5 例,Ⅳ度2 例。DICE组白细胞下降Ⅲ度12例,Ⅳ度4 例;贫血Ⅲ度2 例;血小板下降Ⅲ度3 例,Ⅳ度1 例。胃肠道反应较GOX组为重,Ⅲ度2 例,Ⅳ度1 例。比较两组毒副反应,GOX组在中性粒细胞减少,消化道反应方面明显好于DICE组（P<0.05）。 而DICE组出现未出现末梢神经毒性病例。结论:GOX方案二线治疗复发或难治性非霍奇金淋巴瘤是较为安全且有效的化疗方案,其远期疗效尚需进一步观察。      

非霍奇金淋巴瘤DICE方案二线治疗疗效观察

非霍奇金淋巴瘤（non—Hodgkin lymphoma，NHL）以化疗为主，其标准方案为环磷酰胺、阿霉素、长春新碱、泼尼松（CHOP），但对CHOP方案耐药或CHOP方案治疗后复发的患者治疗尚没有统一方案，且疗效欠佳。总结我院2002年至今采用DICE方案二线治疗的27例NHL患者，疗效肯定，现报告如下。     

MINE-ESHAP联合方案治疗难治或复发性非霍奇金淋巴瘤28例

 目的　探讨MINE-ESHAP联合方案治疗难治性或复发性非霍奇金淋巴瘤（NHL）的疗效。方法　采用MINE-ESHAP联合方案治疗难治性或复发性NHL 28例。结果　28例患者中,CR 11例（39.3 %）,PR 6例（21.4 %）,SD 5例（17.9 %）,进展或恶化5例（17.9 %）,中位生存时间28.5个月。1例死于骨髓抑制期感染（3.6 %）。不良反应主要为消化道症状和骨髓抑制。结论　MINE-ESHAP方案对部分难治性或复发性NHL患者有效,不良反应可以耐受,可用于对其他化疗方案无效的难治性或复发性NHL。     

MINE-ESHAP联合方案治疗难治或复发性非霍奇金淋巴瘤28例

目的 探讨MINE-ESHAP联合方案治疗难治性或复发性非霍奇金淋巴瘤(NHL)的疗效.方法 采用MINE-ESHAP联合方案治疗难治性或复发性NHL 28例.结果 28例患者中,CR 11例(39.3%),PR 6例(21.4%),SD 5例(17.9%),进展或恶化5例(17.9%),中位生存时间28.5个月.1例死于骨髓抑制期感染(3.6%).不良反应主要为消化道症状和骨髓抑制.结论 MINE-ESHAP方案对部分难治性或复发性NHL患者有效,不良反应可以耐受,可用于对其他化疗方案无效的难治性或复发性NHL.     

MINE-ESHAP联合方案治疗难治或复发性非霍奇金淋巴瘤28例

目的 探讨MINE-ESHAP联合方案治疗难治性或复发性非霍奇金淋巴瘤(NHL)的疗效.方法 采用MINE-ESHAP联合方案治疗难治性或复发性NHL 28例.结果 28例患者中,CR 11例(39.3%),PR 6例(21.4%),SD 5例(17.9%),进展或恶化5例(17.9%),中位生存时间28.5个月.1例死于骨髓抑制期感染(3.6%).不良反应主要为消化道症状和骨髓抑制.结论 MINE-ESHAP方案对部分难治性或复发性NHL患者有效,不良反应可以耐受,可用于对其他化疗方案无效的难治性或复发性NHL.     

DICE方案治疗难治和复发性非霍奇金淋巴瘤的疗效分析

背景与目的:目前对于难治性和复发性非霍奇金淋巴瘤(non-Hodgkin)slymphoma,NHL)尚无标准解救化疗方案,本文旨在探讨DICE方案(地塞米松,异环磷酰胺,顺铂及VP-16)治疗难治和复发性NHL的疗效和不良反应。方法:80例难治和复发性NHL患者,其中T细胞NHL25例,B细胞NHL55例,既往均接受过6个周期的CHOP化疗方案无缓解。现采用DICE方案对患者进行解救治疗,并对毒副反应加以评估、预防及治疗。结果:80例患者接受6个周期DICE方案化疗后,总体有效率为56.3%,完全缓解率为27.5%;T、B细胞NHL有效率分别为48.0%、60.0%,完全缓解率为16.0%、32.7%(P>0.05);经DICE方案治疗的患者出现骨髓抑制、消化系统反应、脱发以及电解质紊乱发生率增高,经过治疗均恢复,无治疗相关死亡。结论:DICE方案治疗难治和复发性NHL有效。     

DICE方案治疗复发或难治中高度恶性非霍奇金淋巴瘤的疗效分析

目的: 目前对于复发或难治中高度恶性非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)尚无标准解救化疗方案,本文旨在探讨DICE方案(地塞米松、异环磷酞胺、顺铂及VP-16)治疗复发或难治中高度恶性NHL的疗效和不良反应。 方法: 22例复发或难治中高度恶性NHL患者,既往均接受过2～6个周期的CHOP化疗方案无缓解或复发。现采用DICE方案化疗,中位疗程数4个周期(2～7个周期),所有患者均可评价疗效和不良反应。对患者进行解救治疗,并对毒副反应加以评估、预防及治疗。 结果: 22例患者DICE方案化疗后,总有效率为63.6%,完全缓解率为40.9%;T、B细胞NHL有效率分别为75.0%、57.1%,完全缓解率分别为37.5%、42.9%(P>0.05);LDH升高、伴有巨大肿块是影响复发耐药患者近期疗效的高危因素(P均<0.05)。经DICE方案治疗的患者,骨髓抑制、消化系统反应、脱发是较常见的并发症,经过治疗均恢复,无治疗相关死亡。 结论: DICE方案治疗难治和复发性NHL有效。     

DACE方案治疗难治复发性非霍奇金淋巴瘤的临床疗效

背景与目的:难治复发性非霍奇金淋巴瘤二线解救方案甚多,目前国内外尚无标准的解救方案。本研究旨在观察DACE方案治疗难治复发性非霍奇金淋巴瘤的治疗疗效及毒副作用。方法:我院从2001年5月至2006年5月对61例难治复发性非霍奇金淋巴瘤患者,采用DACE方案进行化疗,具体为:顺铂20mg/m2,静脉滴注,第1～5天;足叶乙甙100mg,静脉滴注,第1～5天;阿糖胞苷150mg,静脉滴注,第1～3天;地塞米松15mg/m2,静脉滴注,第1～5天,3周为一疗程。按照WHO疗效评价标准及WHO对抗癌药物急性与亚急性反应的分度标准进行临床疗效及毒副作用评估。结果:两周期后有效率63.9%,4周期后有效率72.1%。有效患者中位缓解时间4.7个月(1～58个月),1年生存率29.5%,2年生存率21.3%。主要毒副作用为Ⅲ～Ⅳ度骨髓抑制49.1%,患者能够耐受。结论:DACE方案可作为难治复发性非霍奇金淋巴瘤的解救方案之一。     

MIEP方案治疗复发或难治非霍奇金淋巴瘤疗效报告

目的　观察MIEP化疗方案治疗复发或难治非霍奇金淋巴瘤 (NHL)临床疗效和毒副作用。方法　 3 5例复发或难治NHL患者给予米托蒽醌 (MIT) 10mg/m2 静滴 ,d1;异环磷酰胺 (IFO) 1 2g/m2 静滴 ,d1～ 4,美司那 (Mesna) 40 0mg用IFO后 0、4、8h静推 ;依托泊甙 (VP 16) 65mg/m2 静滴 ,d1～ 4;强的松 (PRED) 10 0mg口服 ,d1～ 5。 2 1～ 2 8天为一周期 ,至少 3个周期。结果　MIEP方案化疗的疗效CR 2 8 6% ,PR 3 7 1% ,总有效率 65 7%。中位生存期为 19个月。毒副作用主要为骨髓抑制 ,白细胞减少发生率为 10 0 % ,其中Ⅲ度、Ⅳ度发生率为 71 4%。结论　MIEP方案治疗复发或难治非霍奇金淋巴瘤有效率高 ,毒性反应可耐受。     

ACES方案治疗难治性或复发性非霍奇金淋巴瘤的疗效观察

目的 应用阿糖胞苷(Ara-c)、顺铂(cisplatin)、足叶乙甙(etoposide),类固醇激素(storid)联合化疗治疗难治性或复发性非霍奇金淋巴瘤(NHL),观察疗效及毒副反应.方法 12例难治性或复发性NHL,给予Ara-c 500 mg,d5,顺铂40 mg,d1-3,足叶乙甙(VP16-213)100 mg,d1-4,Dex 40 mg,d1-5联合化疗.结果 总有效率(CR PR)为66.6%.毒副反应主要是骨髓抑制,经G-CSF治疗均可恢复.结论 与NHL经典方案无交叉耐药的ACES补救方案是治疗难治性或复发性非霍奇金淋巴瘤有效、安全的治疗方案.     

我国复发难治性淋巴瘤治疗策略分析

对比分析国内外淋巴瘤权威指南中关于不同类型复发难治性淋巴瘤的诊治信息,并收集国内外复发难治性淋巴瘤诊治的循证医学证据.与国外指南相比,我国的复发难治性淋巴瘤治疗方案包括病种较少;内容相对简单,操作力不强;未注明循证医学研究证据,可参考性有待提高.我国复发难治性淋巴瘤的定义、诊断标准有待规范,临床实践指南内容有待扩充,应开展复发难治性淋巴瘤的高质量临床研究,充分收集循证医学研究证据,提高临床实践指南的可操作性,规范复发难治淋巴瘤诊治.     

Results of a Salvage Regimen in Refractory or Relapsed Non-Hodgkin's Lymphoma

After therapy with adriamycin-containing regimens, relapsed or refractory non-Hodgkin's lymphomas (NHL) have a very poor prognosis. Although high dose chemotherapies are widely employed, their related costs and the controversial results achieved justify the development of new second-line conventional therapies. Forty-three patients with relapsed or refractory NHL were consequently treated with an outpatient polychemotherapy schedule including ifos-famide, mitoxantrone and etoposide on day 1, and vindesine, cisplatinum and cytosine ara-binoside on day 15. The courses were repeated on day 29. All of the patients were pretreated with at least one chemotherapy regimen. Twenty-two patients had diffuse large cell lymphoma, 8 had bone marrow involvement, and 17 altered baseline lactate dehydrogenase (LDH) values. After a median number of 4 cycles (range 2-8), we registered 20 complete (46%) and 4 partial remissions, for an overall remission rate of 56% (95% confidence interval: 40-71%). All of the responses occurred in patients who had achieved at least partial remission during first-line therapy. Four patients are long term responders after 31, 39, 49 and 52 months, and are possibly cured. Univariate analysis of prognostic factors showed that baseline LDH values and response to front-line therapy significantly affected both time to disease progression and survival, whereas the number of previous treatments given, significantly affected only the time to progression. Therapy was administered in an out-patient setting and no life-threatening toxicity was observed. Side effects consisted of nausea/vomiting, alopecia and reversible myelosuppression. The results suggest that different treatment strategies for relapsed and refractory patients should be considered on the basis of prognostic factors. The proposed schedule may be potentially curative in a subgroup of relapsed patients at better risk; poor risk refractory patients should be considered for investigational trials involving high-dose chemotherapy.     

Chemotherapy with Irinotecan (CPT-11), a Topoisomerase-I Inhibitor, for Refractory and Relapsed Non-Hodgkin's Lymphoma

Irinotecan hydrochloride (CPT-11), a DNA topoisomerase-I inhibitor, is now widely used in the treatment of various solid tumors, including colorectal, gastric, breast, lung, and ovarian cancer. Despite the good response shown in the late phase-II study, CPT-11 was not often employed in the treatment of malignant lymphoma, mainly because of severe leukopenia and diarrhea caused by the recommended schedule: 40 mg/m² of CPT-11 on days 1 to 3, 8 to 10, 15 to 17, then discontinued for at least 2 weeks. In clinical use, administration of CPT-11 had to be ceased on days 15 to 17 in almost all cases, and on days 8 to 10 in a considerable number of patients. Subsequently, a lower dose schedule (less than 40 mg/m²) was developed. Our phase II trial employing a reduced dose of CPT-11 on days 1 and 2, plus ADM on day 3 with 3-week interval in patients with refractory and relapsed NHL showed a fairly good response of relapsed B-cell lymphoma and a substantial response of T-cell lymphoma with acceptable toxicity. The combination of a topoisomerase-I inhibitor (CPT-11) and a topoisomerase-II inhibitor is an interesting concept for the treatment of NHL. Another phase II trial in combination with CPT-11 and other anti-cancer drugs, particularly cisplatin or topoisomerase-II inhibitors, is warranted. A superior salvage chemotherapy regimen could be found in the future by investigating combinations of low-dose CPT-11 and cisplatin or topoisomerase-II inhibitors.     

Outcome of Patients with Relapsed or Refractory Non-Hodgkin's Lymphoma Referred for Autologous Bone Marrow Transplantation

Fifty-one patients with relapsed or refractory intermediate- or high-grade non-Hodgkin's lymphoma were referred for autologous bone marrow transplantation (ABMT). The primary criterion for eligibility was sensitivity to conventional-dose salvage chemotherapy. Of 47 patients who received salvage chemotherapy, 30 demonstrated chemotherapy-sensitive disease. Six eligible patients did not undergo ABMT for various reasons. A total of 24 patients underwent ABMT, with etoposide, melphalan ± total body irradiation as the intensive therapy regimen. There was one early treatment-related death and three non-responders. Of the remaining patients, 9 relapsed, while 11 remain in continuous complete remission (CR) at a median follow-up of 21 months after transplant (range 5-37 months). Two patients with chemosensitive disease and bone marrow involvement underwent allogeneic BMT with marrow from HLA-identical siblings. Both are in continuous CR at 6 and 12 months follow-up. Of the 25 patients who did not undergo ABMT, all have died (median survival 5 months).

The results indicate that approximately one-half of relapsed or refractory aggressive histology lymphoma patients referred for ABMT eventually undergo transplantation, if chemotherapy-sensitive relapse is the major criterion for eligibility. Approximately 25% of the referred patients may become long-term disease-free survivors with this approach. Reports of marrow transplant series should include all patients referred for ABMT as the denominator for calculating disease-free survival in order to reduce the bias of patient selection.     

BEPP方案治疗复发与难治性非霍奇金淋巴瘤近期疗效

目的　观察平阳霉素 (PYM)、顺铂 (DDP)、足叶乙甙 (VP -16)联合化学治疗复发与难治性非霍奇金淋巴瘤 (non Hodgkin’slym phoma ,NHL)的近期疗效与毒性。方法　 2 7例中 ,中度恶性 11例 ,高度恶性 16例 ,中位年龄 47 3 4岁 ;难治性 11例 ,复发性NHL 16例。治疗方案 :DDP 40mg/m2 静滴d1～ 3 ,VP -1610 0mg/d静滴d1～ 5 ,PYM 10mg/d肌注d1,3 ,5 ,Pred 10 0mg/d口服d1～ 5 ,同时予以辅助止吐治疗及充分水化及利尿 ,2 1天为一个周期 ,连续应用 2个周期以上评价疗效。结果　 2 7例总缓解率 66 7% ,其中CR 7例 ,PR 11例 ;主要毒副反应为骨髓抑制与脱发 ,骨髓抑制多为Ⅰ～Ⅱ度 ,脱发 10 0 %。结论　BEPP方案治疗复发与难治性NHL疗效满意 ,不良反应轻 ,安全可靠     

含吉西他滨联合化疗方案对难治或复发非霍奇金淋巴瘤的疗效观察

目的 观察含吉西他滨联合化疗方案治疗难治或复发非霍奇金淋巴瘤的疗效.方法 将76例非霍奇金淋巴瘤患者根据治疗过程中是否应用吉西他滨分为对照组(非吉西他滨组)和观察组(吉西他滨组)各38例.对比两组临床疗效及不良反应.并比较B细胞与T细胞型难治复发非霍奇金淋巴瘤患者应用吉西他滨方案的疗效差异.结果 两组ORR及CR比较,差异无统计学意义(P＞0.05).观察组PR显著优于对照组,差异具有统计学意义(P＜0.05).两组年龄＞ 60岁患者ORR、CR及PR比较,差异无统计学意义(P＞0.05).观察组B细胞型患者ORR为42.86％,与T细胞型患者ORR 35.29％比较,差异无统计学意义(P＞0.05).观察组Ⅲ～Ⅳ级不良反应中骨髓抑制与对照组比较,差异无统计学意义(P＞0.05);观察组Ⅲ～Ⅳ级不良反应中胃肠道反应发生率与对照组比较,差异有统计学意义(P＜0.05).结论 难治或复发NHL患者应用含吉西他滨方案联合化疗,PR率优于不合吉西他滨方案,并且Ⅲ～Ⅳ级胃肠道反应发生率低.T细胞型患者应用含吉西他滨方案化疗可得到与B细胞型相当疗效.     

Outcomes of Transplant-Eligible Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Salvage Chemotherapy: The Gustave Roussy Experience

IntroductionAfter failure of frontline therapy, patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) that does not respond to first-line salvage chemotherapy can be recommended second-line salvage chemotherapy. The available literature in this regard is weak, although many centers routinely offer this type of second-line salvage chemotherapy to their patients.Patients and MethodsThis retrospective study included transplant-eligible patients with RR-DLBCL treated at Gustave Roussy between January 2008 and April 2020. Eligible patients were those who received second-line salvage chemotherapy using R-DHAP or R-ICE in patients who experienced an insufficient partial response, stable disease, or progressive disease in response to first-line salvage chemoimmunotherapy using an alternative regimen.ResultsForty-six RR-DLBCL patients received second-line salvage regimen, which yielded an objective response rate of 33%, median progression-free survival of 2.1 months, and overall survival of 11.4 months. Twelve patients proceeded to autologous stem-cell transplantation (ASCT), of whom 70% remained alive 1 year after ASCT. To explore the impact of transplantation, a multivariate analysis (excluding response to the first-line salvage regimen because this covariate was totally embedded within the transplantation covariate), ASCT was associated with progression-free survival (hazard ratio = 0.16; 95% confidence interval, 0.06-0.42) and overall survival (hazard ratio = 0.27; 95% confidence interval, 0.08-0.88).ConclusionSecond-line salvage chemotherapy with R-DHAP or R-ICE followed by ASCT leads to a favorable outcome in almost one third of patients with RR-DLBCL and offers a median overall survival of approximately 1 year. These data support the administration of second-line salvage chemotherapy followed by ASCT.     

Carfilzomib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma: A Phase I Trial

IntroductionWe designed a multicenter, phase Ib dose-escalation trial of carfilzomib with bendamustine and rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NCT02187133) in order to improve the response rates of this difficult-to-treat population. Chemoimmunotherapy with bendamustine and rituximab has shown activity in a variety of lymphomas, and proteasome inhibitors have demonstrated pre-clinical synergy and early clinical activity in this population. The objectives were to determine the maximum tolerated dose of carfilzomib and the preliminary efficacy of this combination.Patients and MethodsThe protocol followed a 3+3 design of carfilzomib dose escalation combined with standard doses of bendamustine and rituximab. Patients were treated for up to 6 cycles with an interim positron emission tomography/computed tomography after cycle 3.ResultsTen patients were treated on the dose-escalation phase. The study was terminated at a carfilzomib dose of 56 mg/m², and the maximum tolerated dose was not reached. The most common grade 3/4 adverse event was thrombocytopenia. There was 1 dose-limiting toxicity observed, grade 3 febrile neutropenia, and there were no treatment-related deaths. The overall response rate was 40% (complete response rate, 30%), with a median duration of response of 12 months and a median progression-free survival of 2.1 months.ConclusionCarfilzomib in combination with bendamustine and rituximab is a safe and well-tolerated treatment for patients with relapsed/refractory non-Hodgkin lymphoma. Preliminary data indicate that this combination may have efficacy with an acceptable side effect profile in this heavily pre-treated patient population with limited treatment options.