Treatment with rituximab,dexamethasone, high-dose cytarabine,and oxaliplatin (R-DHAOx) produces a strong long-term antitumor effect in previously treated patients with follicular non-Hodgkin's lymphoma

Background

We explored the addition of rituximab to high-dose cytarabine (ara-C), oxaliplatin (L-OHP), and dexamethasone [R-DHAOx], in resistant and relapsed patients with CD20-positive follicular non-Hodgkin's lymphoma.

Methods

Twenty-two patients were included; they were treated previously with one to five chemotherapy regimens, including 13 patients who had also received rituximab. R-DHAOx consisted of rituximab, 375 mg/m², day 1; dexamethasone, 40 mg/d, days one to four; L-OHP, 130 mg/m², day 1; and ara-C, 2000 mg/m² every 12 h, day 2. Courses were repeated every 21 days for eight courses.

Results

Twenty-one patients (95%) achieved a complete response and one had a partial response. Responses were obtained in patients with and without resistance to prior treatment, either alone or combined with rituximab. The median follow-up time was 58.3 months (range, 8.7–92.6 months). Progression-free survival reached a plateau at 84% at 38.2 months. Only two of the 21 complete responders have relapsed. Tumor molecular markers disappeared in all 10 complete responders whose markers were found before treatment. Peripheral neuropathy related to the cumulative dose of L-OHP, and myelosuppression were the most prominent toxic effects.

Conclusions

R-DHAOx is highly active for salvage treatment of patients with follicular non-Hodgkin's lymphoma, and it produces long-term antitumor efficacy.     

大剂量阿糖胞苷治疗儿童急性白血病血药浓度测定及疗效分析

 目的　探讨儿童急性白血病阿糖胞苷（Ara-C）的血浆浓度与临床疗效的关系,为优化Ara-C合理用药提供依据。方法　采用高效液相色谱法（HPLC）检测37例急性白血病患儿在缓解后应用大剂量Ara-C治疗时的Ara-C及其代谢物阿糖尿苷（Ara-U）的血浆浓度和输注速率,并对患儿的治疗反应、缓解情况、治疗相关的感染情况、Ara-C相关的毒副作用以及中远期疗效进行统计分析。结果　Ara-C每次1～2 g／m2静脉滴注2 h,药物浓度在血浆中达高峰时间为2 h,峰浓度为14.37～84.44 μmol／L,平均为（41.42±22.80）μmol／L,中位输注速率为869.57 mg·m-2·h-1,滴注结束后血药浓度迅速下降。Ara-U浓度在Ara-C滴脉滴注结束后30 min达高峰,平均为（253.40±81.49）μmol／L,约为Ara-C峰浓度的6倍以上,但至下次滴注前仅少量残留在体内。37例患儿的中位持续完全缓解时间为29.8（5.0～53.1）个月,3年无瘤生存率为（90.63±5.15）%,治疗相关的感染率为56.8 ％（21／37）,3例（8.1 %）患儿合并重症感染,无治疗相关性死亡,无不能耐受治疗方案而中途退出者。结论　大剂量阿糖胞苷作为儿童急性白血病的缓解后治疗,无体内药物蓄积,毒副反应轻,可有效提高患儿的长期持续完全缓解率及临床治愈率,值得推广应用。     

阿糖胞苷增强急性白血病细胞B7分子表达及激活T细胞的免疫反应

 目的　探讨阿糖胞苷（Ara-C）对急性白血病（AL）细胞B7分子表达和激活T细胞的免疫反应。方法　用流式细胞术检测原代AL细胞B7分子的表达。同时检测Ara-C诱导HL-60细胞 B7分子的表达,进而用RT-PCR方法检测HL-60细胞B7 mRNA表达。MTT法检测诱导后HL-60细胞对人外周血单个核细胞（PBMC）的促增生作用,并用RT-PCR法测定γ-干扰素（IFN-γ）含量。结果　40例AL患者中B7-1阳性1例,B7-2阳性3例、弱阳性4例。Ara-C能显著刺激HL-60细胞 B7表达,诱导后的HL-60细胞显著刺激PBMC增生并产生IFN-γ。结论　原代AL细胞低表达B7-1和B7-2分子。在体外,Ara-C通过诱导HL-60细胞表达B7分子,刺激T淋巴细胞增生,使PBMC分泌IFN-γ增多,显著提高了白血病细胞的免疫原性。     

沙利度胺联合小剂量HA方案治疗老年急性髓系白血病23例

目的:观察沙利度胺联合小剂量HA方案治疗老年人急性髓细胞白血病(AML)的疗效及安全性。方法:回顾分析接受沙利度胺联合小剂量HA方案治疗的老年AML患者23例的临床资料。沙利度胺100mg/d连续口服,小剂量HA方案为高三尖杉酯碱(har)1～2mg/d,静脉滴注,d1～14。阿糖胞苷(Ara-c)25～50mg/d静脉滴注,d1～14。14d为1疗程。1～2疗程结束后评价疗效。治疗1疗程达完全缓解者用常规DA、MA、EA等方案进行巩固治疗,连用2疗程不缓解者则更换方案。观察治疗效果及不良反应。结果:23例患者中,完全缓解7例,部分缓解9例,CR率30.4%,总有效率69.2%。所有患者均顺利完成化疗,不良反应除骨髓抑制外,无严重感染、出血及重要脏器损伤,无早期死亡病例。结论:沙利度胺联合小剂量HA方案治疗老年人AML疗效确切,相对安全,耐受性好。     

CAG与FLAG方案治疗难治或复发急性髓系白血病的疗效初步研究

目的比较分析CAG方案与FLAG方案治疗难治AML的疗效和不良反应。方法 28例患者应用CAG方案,另15例患者采用FLAG方案治疗。所有病例经过1个疗程化疗后评估疗效和不良反应,获得完全缓解(CR)或部分缓解(PR)的有效者均重复原方案化疗;无效者改用其他方案。结果 CAG组28例中13例获得CR,5例获得PR,总有效率64.29%,早期病死率10.71%;FLAG组15例中4例获得CR,5例获得PR,总有效率60%,早期病死率13.33%。2组方案主要不良反应为骨髓抑制。FLAG组在感染、胃肠道反应及肝损等不良反应发生率显著高于CAG组。结论 CAG方案和FLAG方案均为复发难治AML治疗的有效方案,其中CAG方案非血液学不良反应低。     

补虚化瘀方对联合化疗荷瘤小鼠骨髓造血功能的影响

目的观察补虚化瘀方对联合化疗荷瘤小鼠骨髓造血的作用。方法采用P388瘤株造成荷瘤小鼠模型后,再以环磷酰胺、阿糖胞苷腹腔注射获得联合化疗荷瘤小鼠骨髓抑制模型,实验分为正常组、模型组及补虚化瘀方组,进行血常规、骨髓有核细胞(BMC)计数、粒单系祖细胞(CFU-GM)集落计数、骨髓细胞增殖能力测定。结果联合化疗可致荷瘤小鼠血红蛋白(Hb)、白细胞计数(WBC),BMC、CFU-GM集落计数及骨髓细胞增殖能力明显低于正常组(P<0.01),补虚化瘀方可提高联合化疗荷瘤小鼠外周血Hb、WBC数,提高BMC、CFU-GM集落计数及骨髓细胞增殖能力(P<0.01)。结论补虚化瘀方对联合化疗荷瘤小鼠骨髓抑制模型具有保护造血细胞和促进其化疗损害后的修复作用。     

大剂量阿糖胞苷对急性髓性白血病缓解后巩固治疗的影响

目的观察大剂量阿糖胞苷（HD—AraC）（3g/m^2）治疗急性髓性白血病（AML）患者的近期疗效及安全性。方法回顾分析我院血液科收治的应用HD—AraC治疗的12例AML患者的病例资料,治疗方案为AraC3g／m^2,1次／12h,第1、3、5天,连续3—4个疗程,其中2例患者只进行2个疗程。观察治疗后效果。结果全部患者均可耐受,有较好的安全性,中位随访时间为24．1（7—54）个月,随访观察至2012年7月,10例患者处于持续缓解状态,只完成2个疗程的患者复发死亡。全组治疗相关死亡率为0％（0／12）,复发相关病死率为16．7％（2／12）,中位生存期为35．8（7～66）个月,2年总生存率为83．3％（10／12）。结论HD—AraC应用于AML缓解后的巩固化疗疗效较好,有较好的安全性,值得临床更大规模的应用。     

RP-HPLC法测定小鼠各组织中阿糖胞苷及阿糖尿苷浓度

目的:建立在血浆、脑脊液和睾丸组织中同时测定阿糖胞苷及其代谢物阿糖尿苷浓度的反相高效液相色谱法并进行小鼠体检内测定波量长分为析28。0 n方m法,柱:色温谱为柱30为℃X,T进er样ra量C18为,流10动μ相L。为将0.0115 m只o小l.鼠L-随1磷机酸分盐成缓A冲、B液、(Cp H3组=,6分.0)别-乙腹腈腔=注9射5∶阿5,糖流胞速苷为105.09、51 m 0L0.0m、2in 0-010,mg·kg-1,30 min后测定小鼠血浆、脑脊液、睾丸组织中的阿糖胞苷及阿糖尿苷浓度。结果:阿糖胞苷、阿糖尿苷检测浓度线性范围分别为0.25～21.74、0.99～86.96 mg·L-(1r>0.998 8),检测限为0.1～0.4 mg·L-1;平均回收率均≥96%,RSD≤7.19%。阿糖胞苷及阿糖尿苷在小鼠血浆、脑脊液和睾丸组织中的药物浓度有显著性差异,低、中剂量给药组只在血浆中检测出阿糖尿苷。结论:所建立的测定方法简单、快速、准确、重复性好,可为临床上阿糖胞苷和阿糖尿苷血药浓度的监测和药动学研究提供参考。     

Response to cytarabine ocfosfate (YNK01) in a patient with chronic lymphocytic leukemia refractory to treatment with chlorambucil/prednisone,fludarabine, and prednimustine/mitoxantrone

 Cytarabine ocfosfate (YNK01) is a novel orally applicable prodrug of cytosine arabinoside. Recent pharmacokinetic studies have revealed a prolonged release of the cytotoxic agent cytosine arabinoside (araC) from hepatocytes into the systemic circulation, resulting in a half-life of approximately 24 h for araC. The specific pharmacokinetic characteristics of cytarabine ocfosfate lead to a prolonged exposure of leukemic cells to this antineoplastic agent during the 14-day cycle. The oral applicability during outpatient treatment and the sustained antineoplastic activity of araC against slowly proliferating leukemic B-cells suggest that cytarabine ocfosfate might be a useful drug in the treatment of chronic lymphocytic leukemia. Four years after diagnosis of B-CLL, a 50-year-old patient was started on cytarabine ocfosfate. Sequentially, the patient's disease had proved refractory to treatment with chlorambucil/prednisone (31 months), fludarabine (5 months), and prednimustine/mitoxantrone (3 months). These established regimens were discontinued because of increasing lymphocytosis, significant thrombocytopenia, and progressive B-symptoms. Following three cycles of cytarabine ocfosfate B-symptoms resolved, lymphadenopathy disappeared, and thrombocytopenia was significantly reduced. The patient has been free of these symptoms on a dosage of 1500 mg cytarabine ocfosfate/day (cycle of 14 days with intervals of 14–21 days) for 24 months and remains in an ongoing partial remission. Recieved: 25 March 1996 / Accepted: 28 May 1996