盐酸苯达莫司汀治疗利妥昔单抗耐药的B 细胞惰性淋巴瘤多中心Ⅲ期临床研究

目的:评价注射用盐酸苯达莫司汀单药治疗利妥昔单抗治疗失败的B 细胞惰性淋巴瘤的有效性和安全性。方法:2010年4 月至2013年4 月,全国8 个研究中心入组100 例利妥昔单抗治疗失败的B 细胞惰性淋巴瘤患者,接受苯达莫司汀单药治疗（120 mg/m2,d1、2,每21天1 个周期,最多8 个周期）。 主要终点指标为总反应率（ORR ）,次要终点指标包括疾病控制率（DCR ）、无进展生存（PFS）、总生存（OS）及安全性评估。结果:全组100 例患者,中位年龄为56（28～74）岁,共计化疗447 个周期,中位4（1～8）个周期。93例患者完成至少2 个周期治疗,可评价疗效。15例（16.1%）获得完全缓解（CR）,52例（55.9%）获得部分缓解（PR）,22例（23.7%）稳定（SD）,4 例（4.3%）进展（PD）,ORR 为72% ,DCR 为95.7% 。中位随访时间26.6（2～48.4）个月,59例（63.4%）出现疾病进展,中位PFS 为8.53个月（95%CI:6.518～10.542）,1 年PFS 率（40.6 ± 5.3）% 。48例（48%）出现3/ 4 级不良事件,3/ 4 级白细胞减少、中性粒细胞减少、血小板减少发生率分别为26% 、24% 和11% 。结论:苯达莫司汀治疗利妥昔单抗耐药的B 细胞惰性淋巴瘤客观缓解率较高,骨髓抑制为最常见不良反应,系二线治疗惰性B 细胞淋巴瘤的新选择。      

注射用盐酸苯达莫司汀单药治疗利妥昔单抗耐药的B细胞惰性淋巴瘤

  目的  观察注射用盐酸苯达莫司汀单药治疗利妥昔单抗耐药的B细胞惰性淋巴瘤临床疗效及安全性。   方法  25例利妥昔单抗治疗失败的B细胞惰性淋巴瘤患者,接受苯达莫司汀单药化疗（120 mg/m2,d1、2,每21天为1个周期）,评价其近期疗效、无进展生存期与不良反应。   结果  全组25例患者,共计化疗122个周期,中位5个周期。治疗2个周期后均可评价疗效,其中完全缓解（CR/CRu）6例,部分缓解（PR）13例,稳定（SD）3例,进展（PD）3例,总有效率（ORR）为76%,临床受益率（CBR）为88%。截至随访结束,13例患者出现PFS终点事件,中位疗效持续时间（DOR）8个月,中位无进展生存期（PFS）9个月。各亚组间无进展生存期的关系,主要与骨髓受累、血清LDH水平升高有关,差异有统计学意义（P < 0.05）。常见不良反应为骨髓抑制、胃肠道反应和感染,2例患者出现皮疹,1例患者用药5个周期后发生胃癌。   结论  注射用盐酸苯达莫司汀单药治疗利妥昔单抗耐药的B细胞惰性淋巴瘤可提高疗效,且耐受性良好。      

维布妥昔单抗联合化疗治疗32例恶性淋巴瘤的临床观察

目的 回顾性分析维布妥昔单抗联合化疗治疗恶性淋巴瘤的临床疗效和安全性。方法 收集32例CD30阳性淋巴瘤患者资料,其中霍奇金淋巴瘤14例,弥漫大B细胞淋巴瘤2例,成熟T/NK细胞淋巴瘤16例。所有患者均接受化疗联合维布妥昔单抗的治疗至少2周期,每2个周期结束后依据Lugano标准进行疗效评价。结果 4周期治疗后完全缓解率为22%,总缓解率为50%。1～2级毒性16例（50.0%）,3级及以上毒性16例（50.0%）。最常见的不良反应是中性粒细胞减少（50.0%）、肺炎（46.9%）、贫血（43.8%）。最常见的3级及以上不良反应是肺炎（18.8%）和发热（12.5%）。4例因严重不良反应停止使用维布妥昔单抗。结论 维布妥昔单抗治疗复发难治性CD30阳性霍奇金淋巴瘤及外周T细胞淋巴瘤的疗效确切,总体安全性尚可。     

氟达拉滨联合方案治疗复发难治非霍奇金淋巴瘤临床疗效观察

目的观察氟达拉滨联合化疗治疗复发难治非霍奇金淋巴瘤临床疗效及安全性。方法38例复发难治非霍奇金淋巴瘤患者均采用FND方案：氟达拉滨30mg/m² d1~3,米托蒽醌10mg/m² d1,曲安西龙80mg pod 1~5, 28天一周期。结果全组患者CR 8例（21%）,PR 13例（34%）,有效率56%;其中20例复发难治惰性淋巴瘤患者CR7例（35%）,PR9例（45%）,有效率80%; 18例复发难治侵袭性淋巴瘤患者CR 1例（6%）,PR 4例（22%）,有效率28%（ χ²=10.45, P =0.001）。全组患者中位随访22（1~47）月,复发难治惰性淋巴瘤患者中位生存期45（2~47）月,中位无进展生存期18（2~34）月;复发难治侵袭性淋巴瘤患者中位生存期15（2~45）月,中位无进展生存期3（1~22）月。不良反应主要为骨髓抑制和肺感染。结论氟达拉滨联合方案治疗惰性淋巴瘤疗效肯定,对复发难治侵袭性淋巴瘤患者疗效尚可,不失为一种治疗选择。     

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。     

氟达拉滨联合方案治疗恶性淋巴瘤的临床疗效

背景与目的：氟达拉滨是抗病毒药阿糖腺苷的氟化核苷酸类似物，用于治疗慢性淋巴细胞性白血病和复发耐药的惰性淋巴瘤已显示了疗效。本研究的目的为评价氟达拉滨联合方案治疗恶性淋巴瘤的疗效和安全性。方法：2004年1月至2005年11月间本科收治经组织学确诊的接受含氟达拉滨联合化疗的恶性淋巴瘤患者共19例，其中惰性淋巴瘤患者11例，复发的进展性淋巴瘤患者8例。11例惰性淋巴瘤患者中，6例接受了FND（氟达拉滨25mg／m^2Ⅳ d1-3；米托葸醌10mg／m^2Ⅳ d1；地塞米松20mgPOd1～5，每4周重复）方案，5例接受了FC（氟达拉滨25mg／m^2Ⅳ d1-3；环磷酰胺300mg／m^2Ⅳ d1-3，每4周重复）方案。所有进展性淋巴瘤患者均接受了FND方案。结果：接受FND或FC化疗的惰性淋巴瘤患者，有效率91％，完全缓解（CR）率45．5％。进展性淋巴瘤息者中2例达部分缓解（PR），有效率25％。全组有效率63．1％。主要不良反应为骨髓抑制。FND组有69．5％周期发生Ⅲ／Ⅳ度中性粒细胞减少。FC组无Ⅳ度中性粒细胞减少，仅22．2％周期发生Ⅲ度中性粒细胞减少。发生肺部感染4例，外阴尖锐湿疣1例。其他不良反应均为轻度，以消化道反应为主。结论：含氟达拉滨的联合方案，对于惰性淋巴瘤患者具有肯定的疗效，不良反应可以耐受。     

氟达拉滨联合异环磷酰胺治疗利妥昔单抗治疗后复发难治非霍奇金淋巴瘤21例

目的：探讨氟达拉滨联合异环磷酰胺方案对利妥昔单抗治疗后复发难治非霍奇金淋巴瘤（NHL）的治疗效果。方法21例利妥昔单抗治疗后复发难治NHL患者应用氟达拉滨联合异环磷酰胺方案联合化疗,2个月为1个周期,每个周期进行疗效及不良反应评价。结果21例患者中完全缓解4例,部分缓解9例,疾病稳定5例,疾病进展3例,临床总有效率为61.90%（13／21）。其中惰性淋巴瘤的总有效率为71.43%（5／7）,侵袭性淋巴瘤为57.14%（8／14）,两者差异无统计学意义（P＝0.656）。结论氟达拉滨联合异环磷酰胺方案治疗利妥昔单抗治疗后复发难治的NHL患者效果较好。     

氟达拉滨联合化疗治疗20例初治边缘区淋巴瘤的临床观察

目的:探讨氟达拉滨联合化疗方案治疗初治边缘区B细胞淋巴瘤的疗效和不良反应.方法:2005年9月至2010年2月期间,收治经北京肿瘤医院确诊的初治边缘区B细胞淋巴瘤患者20例,其中结外、结和脾边缘区淋巴瘤分别为16例、3例和1例.治疗方法均采用含氟达拉滨的方案,其中采用FC方案(氟达拉滨+环磷酰胺)治疗14例,采用Rituximab(利妥昔单抗,R)-FC治疗6例.所有患者均接受1～6个周期化疗,平均完成为4.3个周期.结果:20例患者中达完全缓解者18例(90%),达部分缓解者2例(10%),总有效率(完全缓解+部分缓解)为100%.所有患者的1年和2年总生存率均为88%,1年和2年无进展生存率均为88%,1年和2年的无瘤生存率均为85%.全组共化疗86个周期,主要不良反应为骨髓抑制和轻度胃肠道反应.51%周期发生白细胞下降,其中9.3%周期发生Ⅲ/Ⅳ度白细胞减少;6例(30%)患者出现血小板下降,年龄≥60岁患者中血小板下降发生率为66.7%(4/6),而<60岁患者中血小板下降发生率为14.3%(2/14),P=0.037;20%周期发生胃肠道反应;8%周期发生轻度肝功能损伤;1例(5%)患者合并肺部真菌感染.结论:氟达拉滨联合环磷酰胺对初治边缘区B细胞淋巴瘤的近期疗效较好,不良反应可耐受,远期疗效值得期待.     

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。      

GemOx±R方案治疗复发或难治的侵袭性非霍奇金淋巴瘤

目的:观察GemOx±R方案治疗复发或难治的侵袭性非霍奇金淋巴瘤（NHL ）的近期疗效和不良反应。方法:经组织学证实的复发或难治的侵袭性29例NHL 患者给予GemOx±R方案:吉西他滨（gemcitabine ）1 000mg/m2,静脉注射,d1、d8;奥沙利铂（oxaliplatin）130mg/m2,静脉注射d1;加/不加利妥昔单抗（rituximab ）375mg/m2,静脉注射,d0。21~28d 为一个周期。每个患者均完成≥2 周期的化疗。结果:29例患者中,总有效率为65.5% ,11例完全缓解（CR）,8 例部分缓解（PR）;B 细胞和T 细胞淋巴瘤患者的有效率分别为68.4% 和60.0% ,差异无统计学意义（P>0.05）;但在B 细胞淋巴瘤中,加用美罗华与否的有效率分别为80.0% 和55.6% ,差异有统计学意义（P=0.043）。 不良反应主要表现为骨髓抑制和胃肠道反应,表现为粒细胞、血小板减少及恶心、呕吐等。结论:GemOx±R方案高效低毒,是针对复发或难治性的侵袭性非霍奇金淋巴瘤安全有效的解救方案。      

A Multicenter,Open-Label,Noncomparative Screening Study of Enzastaurin in Adult Patients With Non-Hodgkin Lymphomas

PurposeTo assess the antitumor activity of enzastaurin in patients with non-Hodgkin lymphomas: T-cell lymphoma (n = 23): cutaneous and peripheral T-cell lymphoma; indolent B-cell lymphomas (n = 19): small lymphocytic, follicular grade 1 or 2, marginal zone lymphomas; and aggressive B-cell lymphomas (n = 15): follicular lymphomas grade 3, aggressive lymphoma with a clinical history. The primary objective was to determine overall tumor response. Secondary objectives included duration of response and safety.Materials and MethodsIn this multicenter, open-label, noncomparative, screening study conducted between December 2007 and February 2009, patients (≥ 18 years) who relapsed after ≥ 1 prior systemic treatment or who were intolerant to standard systemic therapy received 250 mg oral enzastaurin (125 mg tablets twice a day; a 1125-mg loading dose on day 1), in 28-day cycles for up to 2 years unless unacceptable toxicity or progressive disease occurred.ResultsResponses were seen in follicular lymphomas grade 3 (1/5, 20.0%), cutaneous T-cell lymphoma (2/11, 18.2%), small lymphocytic lymphomas (1/7, 14.3%), and aggressive lymphoma with a clinical history (1/10, 10.0%) in this heavily pretreated patient population (median prior therapies range from 4 to 10). Most drug-related toxicities were grade 1/2, the most common being diarrhea, peripheral edema, and pruritus.ConclusionsEnzastaurin was well tolerated but demonstrated modest responses across subgroups in this heavily pretreated patient population.     

Phase I/II and pharmacokinetic study of cladribine with 2-h infusion in Japanese patients with relapsed indolent B-cell lymphoma mostly pretreated with rituximab

We conducted a phase I/II study to investigate the toxicity, pharmacokinetics, and efficacy profiles of cladribine with 2-h intravenous infusion for five consecutive days every four weeks in Japanese patients with relapsed indolent B-cell lymphoma. This was a dose-escalation study to confirm the safety of the doses which have been recommended for Caucasian patients (phase I), and to further evaluate the efficacy and safety (phase II). In the phase I portion for nine patients, no dose-limiting toxicities were observed at levels 1 (0.09 mg/kg/day, n  = 3) and 2 (0.12 mg/kg/day, n  = 6). No appreciable accumulation of plasma cladribine concentration was suggested. We enrolled a total of 20 patients, and an additional 14 patients in the phase II portion at level 2 (0.12 mg/kg/day). Eighteen patients, including 13 with follicular lymphoma, were eligible for efficacy evaluation, and 15 (83%) were pretreated with rituximab. The overall response rate was 50% (9/18; 80% confidence interval, 35–65%), with 11% (2/18) complete response. With a median follow-up of 296 days, the estimated median time to progression for 18 eligible patients was 382 days. The most frequent adverse events were hematologic toxicities, including grade 4 neutropenia. Non-hematologic toxicities were mild. In conclusion, cladribine with 2-h intravenous infusion for five consecutive days every four weeks is effective with acceptable toxicities for Japanese patients with relapsed indolent B-cell lymphoma, including those pretreated with rituximab. ( Cancer Sci 2009; 100: 1344–1350)     

Clinical Observation of FMD Regimen:Fludarabine,Mitoxantrone, Dexamethasone, in Treatment of Non-Hodgkin''s Lymphoma

Objective  To evaluate the clinical effectivity and toxicity of the regimen FMD (fludarabine, mitoxantrone, dexamethasone) in patients with non-Hodgkin’s lymphoma. Methods  Thirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell lymphoma, received FMD. Treatment comprised: fludarabine 25∼30 mg/m² days 1∼3, mitoxantrone 8∼10 mg/m² day 1, and dexamethasone 20∼30 mg/m² days 1∼5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole, fluconazole, acyclovir and immunoglobulin. Results  Of the thirty-two patients treated, the complete response (CR) rate, partial response (PR) rate and overall response (OR) rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7% and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3∼4 neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3∼4 thrombocytopenia. At a median follow-up of 24 (5∼54) months, the 2-year overall-survival rate and progression-free survival rate were (87.5 ± 1.4)% and (83.3 ± 1.6)% respectively. The 2-year OS and PFS rates of the indolent group were (93.75 ± 6.25)% and (87.5 ± 8.54)%. Conclusion  FMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin’s lymphoma, especially in indolent B-cell lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.     

Clinical observation of FMD regimen: Fludarabine,mitoxantrone, dexamethasone,in treatment of non-Hodgkin’s lymphoma

Objective

To evaluate the clinical effectivity and toxicity of the regimen FMD (fludarabine, mitoxantrone, dexamethasone) in patients with non-Hodgkin’s lymphoma.

Methods

Thirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell lymphoma, received FMD. Treatment comprised: fludarabine 25～30 mg/m² days 1～3, mitoxantrone 8～10 mg/m² day 1, and dexamethasone 20～30 mg/m² days 1～5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole, fluconazole, acyclovir and immunoglobulin.

Results

Of the thirty-two patients treated, the complete response (CR) rate, partial response (PR) rate and overall response (OR) rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7% and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3～4 neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3～4 thrombocytopenia. At a median follow-up of 24 (5～54) months, the 2-year overall-survival rate and progression-free survival rate were (87.5 ± 1.4)% and (83.3 ± 1.6)% respectively. The 2-year OS and PFS rates of the indolent group were (93.75 ± 6.25)% and (87.5 ± 8.54)%.

Conclusion

FMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin’s lymphoma, especially in indolent B-cell lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.

     

含美罗华方案治疗B细胞性惰性淋巴瘤34例报告

背景与目的：国外临床研究证实利妥昔单抗（rituximab,商品名美罗华）无论是单药还是与化疗药物联用治疗初治或复发惰性淋巴瘤均取得较好疗效。本研究目的是观察含美罗华方案治疗我国惰性淋巴瘤的疗效和安全性。方法：从1999年3月到2005年1月．共34例经病理确诊的惰性淋巴瘤患者接受含美罗华的方案化疗,中位疗程数5个（3～8个）,单药治疗2例．联合化疗32例。化疗方案包括CHOP16例、FMD5例、CHOPE4例、EPOCH2例、DICE2例、DAHP2例和FN1例。结果：34例患者中30例可评价疗效,总有效（OR）率为93-3％,完全缓解（CR）率为60．0％;22例初治患者可评价疗效,OR率95．4％,CR率66．7％;18例滤泡淋巴瘤患者可评价疗效,OR率为88．9％,CR率为66．7％。中位随访期17个月（4～68个月）．1年无疾病进展生存（progression-freely survival,PFS）率为85-3％。主要不良反应为骨髓抑制,19例患者出现白细胞下降,5例患者血小板下降,其中Ⅲ＋Ⅳ度白细胞和血小板下降4例,2例出现中性粒细胞减少性发热;其它不良反应包括Ⅰ～Ⅱ度恶心呕吐、轻度脱发和肝功能受损等。美罗华输注相关不良反应有Ⅰ～Ⅱ度寒战和发热（发生率20．5％）、皮疹、轻度血压下降和无症状性室性早搏等。结论：美罗华单药或联合化疗治疗惰性淋巴瘤具有良好的临床疗效和安全性。     

Rituximab in lymphoma: a systematic review and consensus practice guideline from Cancer Care Ontario

Rituximab is the first antibody-based therapy approved in cancer. The role of this treatment for non-Hodgkin's lymphoma has evolved significantly since its introduction. We aimed to systematically review the literature on rituximab in non-Hodgkin's lymphoma and provide consensus guidelines as to the rational use of this agent. Validated methodology from the Cancer Care Ontario Program in Evidence-Based Care was applied. A comprehensive literature search was completed by reviewers from the Hematology Disease Site Group of Cancer Care Ontario. Data were abstracted from randomized controlled trials of rituximab-containing regimens for patients with non-Hodgkin's lymphoma. Twenty-three randomized controlled trials (RCTs) of rituximab-based therapy were analyzed. Consistent and clinically important benefits in progression-free and overall survival and were seen in the following settings: (1) addition of rituximab to combination chemotherapy for initial treatment of diffuse large B-cell lymphoma and other aggressive B-cell lymphomas; (2) addition of rituximab to combination chemotherapy for initial and subsequent treatment of follicular lymphoma and other indolent B-cell lymphomas; and (3) use of rituximab alone as extended maintenance therapy in patients with indolent B-cell lymphomas who have responded to initial treatment. The consensus opinion of the Hematology Disease Site Group is that rituximab is recommended for these indications.     

Intermittent 2-Hour-Infusion of Cladribine as First-Line Therapy or in First Relapse of Progressive Advanced Low-Grade and Mantle Cell Lymphomas

Aim of this multicenter-study was to evaluate rate and duration of remissions and to examine toxicity of cladribine in low-grade lymphomas as first-line therapy or in first relapse using intermittent 2-hour-infusion of cladribine. A total of 294 courses, median of 5 courses per patient, were administered to 66 evaluable patients (53 previously untreated, 13 relapsed) with 5 mg/m² cladribine given as intermittent 2-hour-infusion over 5 consecutive days for a maximum of 6 cycles every four weeks. Entities: 26 follicle center, 20 lymphoplasmacytoid, 12 mantle cell, 6 T-cell, 2 marginal zone lymphomas. Fifty of 66 patients responded to cladribine corresponding to an overall response rate of 76% (95% confidence interval (95% CI): 64%-85%) with 38% CR (95% CI: 26%-51%) and a median time of remission duration of 23 months (range 645+). The overall survival rate at 48 months was 72%. For 49 previously untreated patients with B-cell lymphomas the overall response rate was 86% (95% CI: 73%-94%) with a high CR rate of 43% (95% CI: 29%-58%). Response rate for the group of 23 previously untreated patients with follicle center lymphomas was high with 96% overall response (95% CI: 78%-100%) and 57% CR rate (95% CI: 34%-77%). Cladribine also showed activity in patients with mantle cell lymphomas achieving a response rate of 58% (95% CI: 28%-85%). Myelosuppression was the major toxicity with 17% neutropenia grade 3 and 4. Thrombocytopenia was rare with only 2% grade 3 and 4. A prolonged CD4-lymphocy-topenia was observed in all patients. Life threatening complications were not observed. These results confirm the major single-agent activity of cladribine in a large cohort of patients with untreated low-grade lymphomas using the intermittent 2-hour-infusion dosage-regimen. To improve treatment results furthermore, cladribine should be combined with other agents active in low-grade lymphomas.     

Intermittent 2-hour-infusion of cladribine as first-line therapy or in first relapse of progressive advanced low-grade and mantle cell lymphomas.

Aim of this multicenter-study was to evaluate rate and duration of remissions and to examine toxicity of cladribine in low-grade lymphomas as first-line therapy or in first relapse using intermittent 2-hour-infusion of cladribine. A total of 294 courses, median of 5 courses per patient, were administered to 66 evaluable patients (53 previously untreated, 13 relapsed) with 5 mg/m2 cladribine given as intermittent 2-hour-infusion over 5 consecutive days for a maximum of 6 cycles every four weeks. Entities: 26 follicle center, 20 lymphoplasmacytoid, 12 mantle cell, 6 T-cell, 2 marginal zone lymphomas. Fifty of 66 patients responded to cladribine corresponding to an overall response rate of 76% (95% confidence interval (95% CI): 64%-85%) with 38% CR (95% CI: 26%-51%) and a median time of remission duration of 23 months (range 6-45+). The overall survival rate at 48 months was 72%. For 49 previously untreated patients with B-cell lymphomas the overall response rate was 86% (95% CI: 73%-94%) with a high CR rate of 43% (95% CI: 29%-58%). Response rate for the group of 23 previously untreated patients with follicle center lymphomas was high with 96% overall response (95% CI: 78%-100%) and 57% CR rate (95% CI: 34%-77%). Cladribine also showed activity in patients with mantle cell lymphomas achieving a response rate of 58% (95% CI: 28%-85%). Myelosuppression was the major toxicity with 17% neutropenia grade 3 and 4. Thrombocytopenia was rare with only 2% grade 3 and 4. A prolonged CD4-lymphocytopenia was observed in all patients. Life threatening complications were not observed. These results confirm the major single-agent activity of cladribine in a large cohort of patients with untreated low-grade lymphomas using the intermittent 2-hour-infusion dosage-regimen. To improve treatment results furthermore, cladribine should be combined with other agents active in low-grade lymphomas.     

氟达拉滨治疗恶性淋巴瘤 29例报告

背景与目的：氟达拉滨(fludarabine)是近年治疗慢性淋巴细胞白血病和低度恶性淋巴瘤的新药,国外报道Fludarabine治疗低度恶性非霍奇金淋巴瘤(NHL)有效率得到进一步提高。本研究的目的是观察含Fludarabine方案治疗我国NHL的疗效和不良反应。方法：从2001年4月到2003年12月期间,共收治经我院确诊的NHL29例,其中男性18例,女性11例;中位年龄53岁(27～79岁);其中低度恶性组22例,中度恶性组7例。治疗方法均采用含Fludarabine的方案,其中采用FMD(fludarabine,mitoxantrone和dexamethasone)治疗19例,采用Rituximab(美罗华)-FMD治疗3例,其余7例分别采用FD(fludarabine,dexamethasone)、FC(fludarabine,CTX)或单药Fludarabine等治疗。中位疗程数为3(1～6)个。结果：29例NHL中可评价疗效的有25例,其中可评价疗效的低度恶性组21例中,有效率为86％(18／21),完全缓解(CR)率为38％,(8／21);中度恶性组中4例可评价疗效者均为复治患者,Fludarabine方案治疗无效。全组共化疗74个疗程,主要不良反应为骨髓抑制和轻度胃肠道反应,其中自细胞下降发生率为61％(Ⅲ Ⅳ度8％),血小板下降发生率18％(Ⅲ Ⅳ度4％),血红蛋白下降发生率26％,均为轻度,需G—CSF支持占5％疗程,均不需要输红细胞和血小板;轻度恶心、呕吐发生率为20％。5例患者化疗期间感染发热,经处理好转;1例出现轻度肝功能损害、黄疸;1例因发生全身皮疹、发热等过敏反应而停药。结论：含Fludarabine的方案治疗低度恶性NHL效果好,不良反应较轻,值得进一步研究。     

Rituximab combined with cladribine or with cladribine and cyclophosphamide in heavily pretreated patients with indolent lymphoproliferative disorders and mantle cell lymphoma

BACKGROUND: In vitro studies have shown synergistic or additive interactions between rituximab and purine nucleoside analogues. The results of recent clinical trials seem to confirm these preclinical observations. METHODS: For the current study, the authors evaluated the feasibility, efficacy, and toxicity of combined regimens that consisted of either rituximab plus cladribine (2-CdA) (the RC regimen) or RC plus cyclophosphamide (the RCC regimen) in the treatment of patients with heavily pretreated, indolent lymphoid malignancies. Fifty-four adult patients with recurrent or refractory, low-grade non-Hodgkin lymphoma (LG-NHL) and B-cell chronic lymphocytic leukemia (B-CLL) were treated according to the RC/RCC regimens. The RC protocol consisted of intravenous rituximab at a dose of 375 mg/m(2) on Day 1 and 2-CdA at a dose of .12 mg/kg per day on Days 2 through 6. The RCC protocol consisted of rituximab at a dose of 375 mg/m(2) on Day 1, 2-CdA at a dose of 0.12 mg/m(2) on Days 2 through 4, and intravenous cyclophosphamide at a dose of 250 mg/m(2) per day on Days 2 to 4. The RC/RCC courses were repeated at 4-week intervals. RESULTS: Thirty-three patients with B-CLL, 12 patients with LG-NHL and 9 patients with mantle cell lymphoma (MCL) entered the study. Thirty-three patients (61%) had recurrent disease after prior therapy, and 21 patients (39%) had refractory disease. Thirty-one patients were treated on the RC regimen, and 23 patients were treated on the RCC regimen. Six patients (11%) achieved a complete response, and 33 patients (60%) achieved a partial response. The median failure-free survival of responders was 10.5 months. The treatment revealed tolerability, with episodes of severe neutropenia (Grade 3 and 4 [according to World Health Organization criteria]) observed in 6 patients (11%), episodes of Grade 3 and 4 infections observed in 11 patients (20%), and episodes of Grade 3-4 thrombocytopenia observed in 4 patients (7%). CONCLUSIONS: The RC and RCC regimens were highly effective and well tolerated modalities of treatment in heavily pretreated patients with indolent lymphoproliferative disorders.