DHAP方案治疗复发和难治性中、高度恶性非霍奇金淋巴瘤的初步观察

背景和目的:复发和耐药非霍奇金淋巴瘤的治疗十分棘手,国外文献报道DHAP方案取得较好疗效,但国内尚未见报道。我们采用DHAP方案治疗复发和难治性非霍奇金淋巴瘤,进一步评价该方案的疗效及毒性。方法:17例复发和10例难治性非霍奇金淋巴瘤患者接受DHAP方案(顺铂20mg/m2,第1～5天;阿糖胞苷1g/m2,q12h,第1～2天;地塞米松40mg,第1～4天)化疗,3～4周重复一次。4例患者进一步进行了自体外周血干细胞移植支持下的超大剂量化疗。结果:CR8例(29.6%),PR4例(14.8%),有效率为44.4%(12/27)。有效患者中位缓解时间4.8个月。DHAP方案治疗后中位生存时间8.3个月,1年生存率为30.8%,2年生存率为19.3%。主要不良反应为骨髓抑制,主要表现为白细胞下降和血小板下降,Ⅲ～Ⅳ度白细胞下降占59.3%(16/27),其中3例(11.1%)患者因粒细胞缺乏出现感染性发热;Ⅲ～Ⅳ度血小板下降占81.5%(22/27),5例(18.5%)患者进行了预防性血小板输注。结论:DHAP是治疗复发和难治性中高度恶性非霍奇金淋巴瘤的有效方案,但仍存在有效率较低,缓解期较短的缺点,且骨髓毒性严重,尤其是血小板和白细胞下降。对于敏感复发的患者,DHAP方案取得完全缓解后,应争取行外周血干细胞移植支持下的大剂量化疗,以延长缓解期和提高长期生存率。     

利妥昔单抗联合二线化疗药物治疗老年人复发或难治性淋巴瘤

目的 研究利妥昔单抗联合二线化疗药物对老年人复发和难治性非霍奇金淋巴瘤(NHL)的治疗效果及安全性.方法 采用利妥昔单抗联合二线化疗药物治疗复发和难治性NHL患者12例.结果 12例共治疗38个周期,总有效(CR+PR)8例,有效率66.7%,临床收益(CR+PR+SD)11例,收益率91.3%.1年无进展生存率和总生存率分别为41.0%和50.0%.不良反应以自细胞和血小板减少最为常见,但均可耐受.结论利妥昔单抗联合二线化疗方案治疗老年人复发和难治性NHL安全有效,且能耐受.     

Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma

Treatment for patients with refractory or relapsed primary CNS lymphoma (PCNSL) remains unsatisfactory. Topotecan is an intravenous topoisomerase I inhibitor with good CSF penetration and documented efficacy in patients with relapsed systemic non-Hodgkin’s lymphoma. In this study 15 patients with refractory or relapsed PCNSL were treated with intravenous topotecan (1.5 mg/m²) for five consecutive days during each 21-day cycle. All 15 patients had measurable, contrast-enhancing tumor on cranial MRI at the time of relapse. Three (20%) patients achieved a complete response after one, three and four cycles, respectively, while three (20%) patients achieved a partial response after two cycles each, for a total response proportion of 40%. Three patients had stable disease at the end of topotecan treatment. Six patients (40%) had progressive disease during treatment. Median overall survival was 981 days (95% CI: 275, NA) and median progression free survival was 60 days (95% CI: 46, 945). Three out of 15 patients had grade 3 thrombocytopenia. Six out of 15 patients had grade 3 neutropenia, while 5/15 patients had grade 4 neutropenia, and 13/15 patients received g-CSF at some point during treatment. There were no deaths directly related to treatment toxicity. Our study shows that topotecan, as a salvage therapy in patients with relapsed or refractory PCNSL, is associated with an overall response proportion of 40% and should be considered in patients who have failed prior methotrexate-based chemotherapy and/or whole brain irradiation. However, progression is frequent and early and most patients required growth factor support due to myelotoxicity.     

Effective salvage chemotherapy in relapsed or refractory non-Hodgkin's lymphoma

BACKGROUND: Over the last few years, high-dose chemotherapy has been extensivelyinvestigated in relapsing/refractory non-Hodgkin's lymphoma(NHL). However, this approach is reserved to a limited subsetof cases and new conventional-dose second-line chemotherapiesneed to be investigated. PATIENTS AND METHODS: Thirty consecutive out-patients with refractory or recurrentNHL were given polychemotherapy in a regimen consisting of ifosfamide,mitoxantrone and etoposide on day 1 and vindesine, cisplatinumand cytosine arabinoside on day 15: courses were repeated every29 days. Five patients had refractory disease following first-linechemotherapy and 25 were relapsing. RESULTS: The median number of administered cycles was 4 (range 2–8).We observed 16 complete (53%; 95% confidence interval, 34%–72%)and 3 partial remissions, for an overall remission rate of 63%(95% confidence interval, 44%–80%). Responses were seenonly among patients who achieved at least a partial responseduring first-line therapy. The median duration of complete remissionwas 15 months (range 5–47+), whereas median survival ofthe treated patients was 26 months (range 2–50+). Fivepatients were long-term responders after 34+, 35+, 46+, 46+and 47+ months. No-life threatening toxicity was observed. Themain side effects were myelosuppression, nausea/vomiting andalopecia. CONCLUSIONS: The proposed regimen is feasible and effective in terms of completeremission rate and disease-free survival, suggesting that thistreatment may be potentially curative in a subgroup of relapsedpatients with limited tumor burden and normal LDH values. Amore aggressive approach is needed in refractory patients. non-Hodgkin's lymphoma, salvage chemotherapy     

DHAP in combination with rituximab vs DHAP alone as salvage treatment for patients with relapsed or refractory diffuse large B-cell lymphoma: a matched-pair analysis

The addition of rituximab to chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) has been shown to improve outcome in first-line therapy. However, in patients with relapsed or refractory disease, the value of adding rituximab to salvage chemotherapy is less clearly defined. This study performed a matched-pair analysis of patients with relapsed or refractory DLBCL by comparing the combination of dexamethasone, high-dose cytarabine and cisplatin (DHAP) with rituximab to DHAP alone. Sixty-seven patients with relapsed or refractory DLBCL were collected from two prospective phase II trials from Germany and Italy. Twenty-three patient pairs treated with either DHAP in combination with rituximab or DHAP alone could be analysed after matching for important prognostic factors. The addition of rituximab to the DHAP regimen led to higher complete and similar overall remission rates. However, differences with regard to complete remission rates failed to reach statistical significance, thereby necessitating further evaluation of the role of combined immunochemotherapy in this patient population.     

氟达拉滨联合吡柔比星治疗复发难治性惰性非霍奇金淋巴瘤

 目的　探讨FT（氟达拉滨及吡柔比星）方案治疗复发难治惰性非霍奇金淋巴瘤（NHL）的有效性和安全性。方法　复发难治惰性NHL40例,采用FT方案化疗,28 d为1个周期,共6个周期。FND（氟达拉滨、米托蒽醌及地塞米松）方案治疗惰性NHL的数据为对照。结果　FT组40例共治疗228个周期,有效率62.5 %,中位无进展生存期超过20个月,2年总生存率70.0 %,与对照组相似（P＞0.05）;不良反应以中性粒细胞减少（80.0 %）最为常见,但Ⅲ～Ⅳ度中性粒细胞减少症和肺炎的发生率均低于对照组,分别为12.5 %、29.0 %和2.5 %、23.0 %（P＜0.05）。结论　FT方案治疗复发难治惰性NHL安全有效,骨髓抑制轻,感染发生率低。     

川芎嗪联合化疗对复发或耐药非霍奇金淋巴瘤的研究

目的 本研究旨在探讨耐药逆转剂川芎嗪配合化疗治疗复发、耐药非霍奇金淋巴瘤(NHL)的作用及与P-糖蛋白(P-gp)表达的关系.方法 60例经病理组织学证实的复发、耐药的NHL患者随机分入逆转剂组(川芎嗪+化疗)和对照组(化疗),分别采用上述两种方案治疗并分析结果.流式细胞仪法分析P-gp的表达.根据P-gp的表达情况进行亚组分析.结果 56例患者有完整数据可供评估,生存分析示两组间差异无统计学意义(P=0.0651),逆转剂组有效率(ORR)高于对照组(P=0.048).亚组分析P-gp(+)的41例患者,完全缓解或不确定的完全缓解率逆转剂组较对照组有显著优势(33.33%与8.70%,P=0.048);逆转剂组ORR亦优于对照组(61.11%与26.09%),差异均有统计学意义(P=0.024).Kaplan-Meier生存曲线及Log-rank检验显示,逆转剂组无进展生存期较对照组延长,差异有统计学意义(P=0.0464).加用逆转剂川芎嗪仅少数患者出现血压下降,减量后缓解.结论 川芎嗪联合化疗可提高复发、耐药NHL患者化疗的疗效,不良反应较轻,可延长疾病无进展生存期,与P-gp的表达密切相关.     

Comparison of salvage chemotherapy regimen ACES with ESHAP for refractory or relapsed malignant lymphoma

Standard salvage chemotherapy for refractory or relapsed malignant lymphoma has not been defined.The efficacy and feasibility of the ACES regimen, consisting of carboplatin at 100 mg/m(2) on day 1 to 4, etoposide at 80 mg/m(2) on day 1 to 4, high-dose Ara-C at 2 g/m(2) on day 5 and methylprednisolone at 500 mg/day for 5 days, for refractory or relapsed lymphoma were retrospectively reviewed in comparison with the ESHAP regimen.The subjects were 29 patients, including 7 aggressive follicular lymphomas, 16 large B cell lymphomas and 6 Hodgkin lymphomas. Characteristics of patients with ESHAP (19 cases) and the ACES (10 cases) group were as follows: male/female ratio, 10/9 and 3/7; median age, 49 (range, 31-72) and 54 (22-65); and initial clinical stage (I and II / III / IV), 5/8/6 and 1/1/8, respectively. Among the 29 patients, complete response was achieved in 68% (13/19) in ESHAP and 40% (4/10) in ACES.Progression-free survival and overall survival were 31.3% and 34.3%, respectively.Hematological toxicity was not significantly different between the two groups, and renal toxicity was significantly higher in ESHAP (52%) than ACES (0%).We concluded that the ACES regimen had a possibility of effective consolidation therapy for the elderly aiming to undergo autologous stem cell transplantation.     

含美罗华联合方案治疗复发耐药B细胞性非霍奇金淋巴瘤

背景与目的:复发或耐药的B细胞性非霍奇金淋巴瘤(non-Hodgkin slymphoma,NHL)预后不良,二线方案化疗远期生存差;抗CD20单克隆抗体美罗华(rituximab)与CHOP或类似方案联合作为一线方案治疗初治侵袭性淋巴瘤可提高远期生存率,但在二线治疗中的作用尚未确定。本研究初步探讨含美罗华联合方案治疗复发耐药B细胞性NHL的近期疗效和不良反应的情况。方法:中山大学肿瘤防治中心近年应用含美罗华方案治疗35例复发耐药NHL患者,其中男性19例,女性16例,中位年龄53.5岁。PS评分0～1分33例(94.3%)。IPI评分0～1分20例(57.1%),2分7例(20.0%),3分4例(11.4%),4～5分4例(11.4%);病理类型以弥漫大B细胞性为主(23例,占65.7%)。所有患者都接受含美罗华的治疗,每疗程前1天应用,剂量375mg/m2,二、三线挽救化疗方案包括EPOCH、CHOP、DHAP、DICE、IMVP-16和FND等。结果:35例患者中单用美罗华治疗者5例,美罗华联合化疗30例,共化疗102疗程。32例可评价客观疗效,有效率68.8%(22/32),完全缓解(CR)13例(40.6%),3例患者在含美罗华方案治疗后接受局部放疗获CR,3例患者在挽救方案治疗后加用造血干细胞移植获CR。主要不良反应为胃肠道反应、骨髓抑制、脱发等,加用美罗华治疗主要增加畏寒、发热等输注相关反应(5例)。中位随访时间12.5个月(3～69个月),失访2例,全组死亡10例(9例死于疾病进展,1例死于重症乙型性肝炎),中位无进展生存期(PFS)11.8个月(3～33个月)。总的1、2、3年生存率分别为72.9%、62.8%和62.8%。结论:含美罗华方案治疗复发耐药的B细胞NHL有效率高、不良反应可以耐受,值得在更大宗病例中作进一步研究。     

Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma

We designed a multicenter Phase II trial to prospectively evaluate the efficacy and safety of the combination of rituximab with the DHAP regimen (dexamethasone, high-dose cytarabine, cisplatin) in patients who relapsed after or were resistant to a CHOP-like regimen. A total of 53 patients with relapsed or resistant aggressive B-cell NHL were analyzed. The overall response rate was 62.3 percent. With a median follow-up of 24.9 months, median overall and progression-free survivals were 8.5 and 6.7 months, respectively. Immunochemotherapy with rituximab and DHAP proved to be feasible and effective in this patient population.     

Ifosfamide and mitoxantrone (I-M) in relapsed and refractory high grade non-Hodgkin's lymphoma and Hodgkin's disease

Fifty-five patients, initially diagnosed as having advanced high grade non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 32 patients with NHL evaluable for response, 10 (31 per cent) achieved complete remission and five partial remission, giving an overall response rate of 47 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 17 patients with HD evaluable for response, six (35 per cent) achieved complete remission and six partial remission, giving an overall response rate of 71 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. Given the need to offer alternative treatment of patients in these categories, this combination (I-M) is clearly of value in relapsed patients especially where therapeutic options are limited because of previous multi-drug treatment.     

SMILE方案治疗复发难治NK／T细胞淋巴瘤的初步临床报告

 目的　探索SMILE方案治疗NK／T细胞淋巴瘤的疗效和不良反应。方法　2006年11月至2008年2月,5例初治和5例复发NK／T细胞淋巴瘤患者接受SMILE方案（甲氨蝶呤、异环磷酰胺 、左旋门冬酰胺酶、依托泊苷等）化疗。1例患者进一步接受了自体外周血造血干细胞支持下的超大剂量化疗,2例患者进一步接受局部放疗。结果　10例患者中有 8例可以评价疗效,总有效率50 %（4／8）,无完全缓解。其中初治和复发患者有效率均为50 %。主要不良反应为骨髓抑制及氨基转移酶升高,其中Ⅲ～Ⅳ度粒细胞减少占65 %,发热性粒细胞减少占25 %,Ⅲ度氨基转移酶升高占10 %,其他不良反应少见,无治疗相关死亡。26.1 %患者由于严重的不良反应中止治疗。结论　SMILE治疗复发耐药的NK／T细胞淋巴瘤有一定疗效,但不良反应明显,目前尚不能作为复发难治NK／T细胞淋巴瘤的标准一线方案。     

Salvage chemotherapy for relapsed and resistant lymphoma with a carboplatin containing schedule—epic

We have treated 11 patients with relapsed or resistant lymphoma with a combination of Etoposide, Prednisolone, Ifosfamide and Carboplatin (EPIC), obtaining complete responses in two patients and partial responses in four patients for an overall response rate of 54 per cent. The treatment was well tolerated with no toxic deaths and five patients were able to proceed to high dose therapy with autologous bone marrow transplantation (ABMT).     

CIK细胞治疗难治复发性非霍奇金淋巴瘤临床观察

 目的 探讨细胞因子活化杀伤细胞（CIK细胞）用于难治复发性非霍奇金淋巴瘤的安全性及疗效。方法 健康供者及淋巴瘤患者的外周血单个核细胞,经过IFN-γ、CD3单抗和rhIL-2共同作用,体外扩增培养CIK细胞,流式细胞仪检测其免疫表型的改变,MTT法检测CIK细胞的杀伤活性。取培养15～21 d的CIK细胞回输,观察临床疗效及不良反应。结果 健康供者及恶性淋巴瘤患者的外周血单个核细胞可以成功培养出CIK细胞。培养第21天,CIK细胞扩增至52.67～64.81倍。培养期内细胞存活率95 %以上。流式细胞仪检测其免疫表型有明显的变化,CD+3 CD+56细胞比例由培养第0天的0.52 %～3.04 %上升至第21天的48.63 %～75.82 %,而CD+3 CD+8细胞则由21.2 %～33.5 %升至82.26 %～92.32 %。MTT法检测CIK细胞对K562细胞有较高的杀瘤活性,当效靶比为5∶1时,在细胞培养的第21天,CIK对K562细胞的杀伤活力为58.1 %～70.9 %。在4例接受CIK细胞治疗患者中,治疗前后临床症状有明显的改善,T细胞亚群测定显示CD4／CD8比值（1.03±0.24～1.26±0.31）及CD+16 CD+56细胞（10.91±6.23～15.68±7.42）与治疗前相比明显升高。治疗过程中及治疗后患者无明显不良反应。结论 CIK细胞可以成为难治复发性非霍奇金淋巴瘤的有效治疗手段之一。     

改良ＥＳＨＡＰ方案治疗复发和难治性中度侵袭性非霍奇金淋巴瘤的临床观察

目的：观察改良的ＥＳＨＡＰ方案治疗复发和难治性中度侵袭性非霍奇金淋巴瘤（ＮＨＬ）的疗效及安全性。方法：１６例复发和１２例难治性中度侵袭性ＮＨＬ患者接受改良的ＥＳＨＡＰ方案化疗（替尼泊苷６０ｍｇ／ｍ２静滴,第２～５天;甲强龙５００ｍｇ静滴,第１～５天;阿糖胞苷１ｇ／ｍ２静滴,第１天;顺铂：２０ｍｇ／ｍ２静滴,第２～５天）,２１～２８天为１周期,按ＷＨＯ标准评价疗效和毒副反应。结果：２８例中ＣＲ１０例,ＰＲ８例,ＳＤ６例,总有效率为６４.３％。主要毒副反应为骨髓抑制,表现为白细胞减少和血小板减少,其中Ⅲ度白细胞减少为８例,占２８.６％,Ⅳ度为１１例占３９.３％,４例因中性粒细胞减少而出现感染性发热;Ⅲ度血小板减少８例,占２８.６％,Ⅳ度为６例,占２１.４％,４例进行了预防性血小板输注。可逆的Ⅰ度肾功能损伤３例。中位缓解期为６个月（１～１６个月）,中位ＴＴＰ为５个月（２～２４个月）,ＭＳＴ为１８个月（３～５１个月）,３年生存率为２９.０％,３年无病生存率为１７.９％。结论：改良的ＥＳＨＡＰ方案是治疗复发和难治性中度侵袭性ＮＨＬ的有效的解救方案,与传统的ＥＳＨＡＰ方案比较,毒副反应较轻,尤其是骨髓抑制可以接受。     

Phase II study of PEND chemotherapy in patients with refractory/relapsed Hodgkin lymphoma

High-dose chemotherapy with autologous marrow or stem cell rescue (HDC/ASCT) is an effective strategy in patients with relapsed Hodgkin lymphoma. Various chemotherapy regimens have been used for cytoreduction prior to HDC/ASCT. In this study, our objective was to determine the response rate to PEND in a group of patients with relapsed Hodgkin lymphoma. Nineteen patients with relapsed or primary refractory Hodgkin lymphoma underwent treatment with the PEND regimen and received a median of 2 cycles (1 - 6 cycles). The PEND regimen builds on our prior results with ABDIC and consists of prednisone 40 mg/m² orally (PO) daily × 5 days; etoposide 50 mg/m² PO daily × 14 days; mitoxantrone 5 mg/m²/d IV, days 1 and 3; and DTIC 200 mg/m²/d intravenous continuous infusion (CIV) over 24 h, days 1 to 5, via central venous catheter. The treatment was given every 28 days. There were 3 complete responses (16%) and 10 partial responses (53%) yielding a total response rate of 69% (95% C.I. 43%, 87%). Myelosuppression was the predominant toxicity; no deaths were due to toxicity. After achieving maximum response to PEND, 10 eligible patients received a consolidative treatment with HDC/ASCT. All 6 patients who did not respond to PEND died from disease progression whereas 5 of 13 responders were alive after 10 years of follow-up (3 without disease). There were 11 deaths due to disease progression; three from other causes. The initial response to PEND before subsequent ASCT consolidation treatment appears to be associated with survival. All patients who failed to achieve a response have died. We conclude that PEND is an effective treatment strategy in Hodgkin lymphoma patients previously treated with both ABVD and MOPP.     

GDP方案治疗复发难治外周T细胞淋巴瘤临床观察

目的:观察GDP方案治疗19例复发难治外周T细胞淋巴瘤的客观缓解率、不良反应.方法: 19例复发外周T细胞淋巴瘤患者采用GDP方案治疗3周期,观察客观缓解率、主要不良反应.结果: 19例患者CR 1例,PR 8例.RR 47.3%.获得缓解的9例患者,复发型8例,难治型1例.获得缓解的IPI低中危组3例,高中危组5例,高危组1例.低中危组与高危组组间差异显著(P<0.05).主要不良反应是骨髓功能抑制,其中III至IV度为4例(21.1%).III至IV度胃肠道反应为2例(10.5%).结论: GDP方案治疗复发外周T细胞淋巴瘤近期疗效确切,安全可行.     

硼替佐米治疗复发难治性套细胞淋巴瘤的研究进展

 复发难治性套细胞淋巴瘤（MCL）的治疗是临床医师面临的严峻挑战。近年来,蛋白酶体抑制剂硼替佐米的应用给复发难治性MCL患者的治疗提供了新方法。就硼替佐米治疗复发难治性MCL的机制、临床疗效以及MCL细胞对硼替佐米耐药产生的机制和应对策略进行综述。     

Radiotherapy as salvage treatment in patients with Hodgkin's disease or non-Hodgkin's lymphoma relapsing after initial chemotherapy

The prognosis of relapsing Hodgkin's disease (HD) and high grade aggressive non-Hodgkin's lymphoma (NHL) is generally poor since many of these patients fail to respond to second line chemotherapy. Radiation therapy has been reported as an effective but seldom used, alternative treatment. We have observed very encouraging results with salvage radiotherapy in a highly selected group of eight lymphoma patients (six with HD and two with high grade NHL), suffering mainly from nodal relapse. The literature on the use of radiation therapy after chemotherapy failures in HD and NHL is reviewed.     

Aclarubicin-combined combination chemotherapy in patients with refractory or relapsed non-Hodgkin's lymphoma

Patients with lymphoma who became refractory or resistant to standard chemotherapy including anthracyclines were treated with aclarubicin-combined chemotherapy including VP-16, ifosfamide, and carboquone in a multicenter study. Twenty-one patients were entered in this study, and 18 of them were evaluable. The median age was 52 years old (range 27-74), and there were 17 male and 3 female patients. The vast majority of patients were diagnosed as having diffuse lymphoma, of which 10 cases had large cell type. Surface markers were measured in 8 patients, of whom 4 had T-cell lymphoma. Remission was attained in 3 of 18 patients (17%) with one complete and lasting remission with T-cell lymphoma. In conclusion, the response rate in this study was poor, but this type of combination chemotherapy might be considered in patients with T-cell lymphoma.