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1.
BACKGROUND: A prospective, single-arm, open-label, nonrandomized Phase 2 study of combined fludarabine and mitoxantrone (FM) plus radioimmunotherapy was conducted to evaluate efficacy and safety in patients with untreated, indolent, nonfollicular non-Hodgkin lymphoma (NHL). METHODS: Between February 2005 and June 2006, at their institute, the authors treated 26 eligible patients with previously untreated, indolent, nonfollicular NHL (10 marginal zone lymphomas, 8 lymphoplasmacytic lymphomas, and 8 small lymphocytic lymphomas) using a novel regimen that consisted of 6 cycles of FM chemotherapy followed 6 to 10 weeks later by yttrium-90 (90Y) ibritumomab tiuxetan. RESULTS: After FM chemotherapy, the overall response rate was 80.5% and included a 50% complete remission (CR) rate (13 patients) and a 30.5% partial remission (PR) rate (8 patients). Of the 20 patients (13 with CR and 7 with PR) who were evaluable (at least a PR with normal platelet counts and bone marrow infiltration <25%) for subsequent 90Y ibritumomab tiuxetan, 100% obtained a CR at the end of the entire treatment regimen. At a median follow-up of 20 months, the estimated 3-year progression-free survival rate was 89.5%, and the estimated 3-year overall survival rate was 100%. The 90Y ibritumomab tiuxetan toxicity included grade >or=3 hematologic toxicity in 16 of 20 patients; the most common grade >or=3 toxicities were neutropenia (11 patients) and thrombocytopenia (16 patients) (adverse events were graded according to the World Health Organization criteria for toxicity). Transfusions of erythrocytes and/or platelets were given to 5 patients. CONCLUSIONS: The current study established the feasibility, tolerability, and efficacy of the FM plus 90Y ibritumomab tiuxetan regimen for the treatment of patients with untreated, indolent, nonfollicular NHL.  相似文献   

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BACKGROUND:

Currently, no standard therapy exists for patients with relapsed and/or refractory non‐Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients.

METHODS:

In a 2‐step, open‐label study, CLO (as a 1‐hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m2 to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression.

RESULTS:

Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab‐refractory. The MTD for CLO was 4 mg/m2. The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab‐refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow‐up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment‐related mortality was observed.

CONCLUSIONS:

Single‐agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab‐refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013). Cancer 2011. © 2010 American Cancer Society.  相似文献   

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The nasal type of extranodal natural killer/T‐cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol‐asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T‐cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2‐year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression‐free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment‐related deaths. These results will require confirmation in larger prospective trials.  相似文献   

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BACKGROUND:

Bendamustine hydrochloride is a novel alkylating agent. In this multicenter study, the authors evaluated the efficacy and toxicity of single‐agent bendamustine in patients with rituximab‐refractory, indolent B‐cell lymphoma.

METHODS:

Eligible patients (N = 100, ages 31‐84 years) received bendamustine at a dose of 120 mg/m2 by intravenous infusion on Days 1 and 2 every 21 days for 6 to 8 cycles. Histologies included follicular (62%), small lymphocytic (21%), and marginal zone (16%) lymphomas. Patients had received a median of 2 previous regimens (range, 0‐6 previous regimens), and 36%were refractory to their most recent chemotherapy regimen. Primary endpoints included overall response rate (ORR) and duration of response (DOR). Secondary endpoints were safety and progression‐free survival (PFS).

RESULTS:

An ORR of 75% (a 14% complete response rate, a 3% unconfirmed complete response rate, and a 58% partial response rate) was observed. The median DOR was 9.2 months, and median PFS was 9.3 months. Six deaths were considered to be possibly treatment related. Grade 3 or 4 (determined using National Cancer Institute Common Toxicity Criteria [version 3.0.19]. reversible hematologic toxicities included neutropenia (61%), thrombocytopenia (25%), and anemia (10%). The most frequent nonhematologic adverse events (any grade) included nausea (77%), infection (69%), fatigue (64%), diarrhea (42%), vomiting (40%), pyrexia (36%), constipation (31%), and anorexia (24%).

CONCLUSIONS:

Single‐agent bendamustine produced a high rate of objective responses with acceptable toxicity in patients with recurrent, rituximab‐refractory indolent B‐cell lymphoma. Cancer 2010. © 2010 American Cancer Society.  相似文献   

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BACKGROUND: The management of recurrent or refractory Hodgkin lymphoma (HL) remains challenging. The objective of this phase 2 trial was to investigate the activity of gemcitabine in combination with rituximab in patients with recurring or refractory HL. METHODS: Patients were considered eligible if they had recurring or refractory HL, had received >or=2 prior chemotherapy regimens, had an Eastern Cooperative Oncology Group (ECOG) performance status 相似文献   

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Overexpression of programmed death‐1 (PD‐1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD‐1‐blocking antibody that inhibits the PD‐1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR). The study was commenced in March 2015. We report data obtained at a cutoff of 16 March 2016, at which time 11 patients were still receiving nivolumab. The median (range) duration of treatment and follow‐up were 7.0 (1.4–10.6) months and 9.8 (6.0–11.1) months, respectively. All 17 patients had previously received brentuximab vedotin. The ORR was 81.3% (95% confidence interval [CI]: 54.4–96.0%; 13/16 patients), with complete remission and partial remission in 4 and 9 patients, respectively. The overall survival (OS) and progression‐free survival (PFS) rates at 6 months were 100 and 60.0% (95% CI: 31.8–79.7%), respectively; the median OS and PFS were not reached. The most common adverse events (AE) were pyrexia (41.2%), pruritus (35.3%), rash (35.3%) and hypothyroidism (29.4%). Four patients (23.5%) experienced grade 3 or 4 AE, but most AE were of grade 1 or 2. In conclusion, nivolumab is a potentially effective and tolerable treatment option for Japanese patients with relapsed/refractory classical Hodgkin lymphoma previously treated with brentuximab vedotin.  相似文献   

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目的 观察奥沙利铂(L-OHP)联合阿糖胞苷(Ara-C)及地塞米松(DXM)对难治性或复发性非霍奇金淋巴瘤(NHL)的疗效及患者不良反应.方法 L-OHP 130 mg/m2,静脉滴注,第1天;Ara-C 2000 mg/m2,静脉滴注,1次/12h,第2天;DXM 40 mg/d,静脉推注,第1天至第4天.每3~4周为1个化疗周期,治疗22例难治性或复发性NHL患者,每例患者治疗≥3个周期评价疗效.结果 22例中的1例于化疗第1周期后死于疾病进展.可评价的21例中13例(61.9%)治疗有效,其中完全缓解(CR)9例(42.9%),部分缓解(PR)4例(19.0%).21例化疗共86个周期,患者不良反应主要表现为轻度胃肠道反应78次(90.7%),中性粒细胞缺乏41次(47.7%),血小板减少61次(70.9%),贫血33次(38.4%).可逆性周围神经病变12例(57.1%).未发现明显肾功能异常者.结论 L-OHP联合Ara-C及DXM对难治性或复发性NHL有较好的近期疗效,其不良反应可以耐受.  相似文献   

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BACKGROUND.

Administration of salvage chemotherapy to patients with relapsed or refractory lymphoma is associated with significant toxicity. Vinorelbine and gemcitabine are novel chemotherapeutic agents with minimal overlapping toxicity. We present a phase 2 study of vinorelbine and gemcitabine with or without ifosfamide administered in an ambulatory care setting for relapsed or refractory lymphoma.

METHODS.

Ninety patients were enrolled. Group 1 comprised patients with “good” risk disease, Group 2 comprised patients with “high” risk disease, and Group 3 comprised patients relapsing after prior stem cell transplant. Patients in Group 1 and Group 3 received vinorelbine and gemcitabine with filgrastim support (VGF); those in Group 2 received the above regimen with ifosfamide (FGIV). We incorporated a standardized interim evaluation with dose escalation for patients with suboptimal response after 2 cycles.

RESULTS.

Toxicities were acceptable. Febrile neutropenia was uncommon: 7% after VGF (7 of 107 cycles) and 19% for FGIV (26 of 148 cycles). Unplanned admissions occurred in 23 of 107 cycles (21%) after VGF and 50 of 148 (34%) after FGIV. Overall response for Groups 1, 2 and 3, respectively was 76%, 39% and 50%, with median overall survival of 28, 9 and 30 months.

CONCLUSIONS.

Vinorelbine‐based and gemcitabine‐based chemotherapy is effective in the salvage setting against lymphoma and can be administered in an ambulatory setting. Cancer 2008. © 2008 American Cancer Society.  相似文献   

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BACKGROUND: The aim of the study was to determine factors affecting the toxicity and efficacy of rituximab monotherapy in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma (MCL). PATIENTS AND METHODS: A total of 90 patients were enrolled and treated with rituximab infusions at 375 mg/m2 once weekly for 4 weeks. Central pathology review revealed that histologically, 81 patients had indolent B-cell lymphoma or MCL: 59 with follicular lymphoma, 17 with MCL, four with marginal zone lymphoma and one with lymphoplasmacytoid lymphoma. Of these, four were ineligible due to violation of other eligibility criteria. Pre-treatment variables affecting toxicities were analyzed for all 90 patients, and those affecting response and progression-free survival (PFS) were analyzed for 77 eligible patients with confirmed indolent B-cell lymphoma or MCL. The relationship between serum rituximab levels and efficacy was also analyzed for 66 eligible patients. RESULTS: Hematological toxicities (grade > or =3) occurred more frequently in females (P <0.05), and thrombocytopenia and leukopenia were more frequent in patients with high lactate dehydrogenase (LDH) levels (P <0.05). Non-hematological toxicities (grade > or =2) were more frequent in patients with extranodal disease or bone marrow involvement. The overall response rate (ORR) in patients receiving one prior chemotherapy regimen was higher than those receiving two or more regimens (P <0.05). The median PFS was shorter in MCL patients, in those with extranodal disease, or in those receiving two or more prior chemotherapy regimens (P <0.01). The PFS intervals of patients with higher serum rituximab levels (> or =70 microg/ml) immediately before the third infusion were longer than in other patients (P <0.01). CONCLUSIONS: Several prognostic factors and serum rituximab levels are useful for predicting the toxicity and efficacy of rituximab monotherapy.  相似文献   

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DHAP方案治疗复发难治性非霍奇金淋巴瘤的临床疗效观察   总被引:7,自引:3,他引:4  
为了观察DHAP方案治疗复发难治性非霍奇金淋巴瘤(non Hodgkin’slymphoma,NHL)的临床疗效和不良反应,选择复发难治性NHL患者34例,采用DHAP方案化疗:DDP100mg/m2,静脉滴入3h,d1;Ara C2g/m2,静脉滴入3h,d2,每12h1次;DXM40mg/d,口服或静脉推注,d1~d4。21~28d为1周期,共完成1~6个周期,中位周期数为3.5。34例患者CR11例(32.4%),PR6例(17.6%),SD13例(38.2%),PD4例(11.8%),总有效率为50%(17/34)。主要毒副反应为血细胞下降和消化道反应,其白细胞Ⅲ~Ⅳ度下降发生率为52.9%(18/34),血小板Ⅲ~Ⅳ度下降发生率为73.5%(25/34),Ⅰ~Ⅱ度消化道反应为14.7%(5/34),其他不良反应少见。初步研究结果显示,DHAP方案是治疗复发难治性NHL的有效解救化疗方案,缓解率高,不良反应可以耐受,值得临床进一步观察。  相似文献   

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Wang M  Burau KD  Fang S  Wang H  Du XL 《Cancer》2008,113(11):3231-3241

BACKGROUND.

There is a lack of research on ethnic disparities in survival among patients with non‐Hodgkin lymphoma (NHL), although these disparities have been documented for patients with many other tumors.

METHODS.

A retrospective cohort of 13,321 patients diagnosed with incident NHL at age ≥65 years from 1992 to 1999 were identified from the Surveillance, Epidemiology, and End Results (SEER)‐Medicare linked database with 11 years of follow‐up. Of these patients, 11,868 were Caucasians, 533 were African Americans, and 920 were other ethnicities. A time‐to‐event Cox regression model was used to examine the relative risk of all‐cause and disease‐specific mortality.

RESULTS.

A larger proportion (72.2%) of African Americans were in the poorest quartile of socioeconomic status as measured by the poverty level compared with 21.8% of Caucasians, and 43.2% of African Americans received chemotherapy compared with 52.4% of Caucasians (P < .01). Hazard ratio of all‐cause and NHL‐specific mortality increased significantly with age, advanced stage, higher comorbidity scores, and poorer socioeconomic status. Patients receiving either chemotherapy or radiotherapy or both were significantly less likely to die. After taking into account differences in treatment, comorbidity, and socioeconomic status, there was no statistically significant difference in the risk of all‐cause (hazard ratio, 0.97; 95% confidence interval, 0.88‐1.08) and disease‐specific mortality (hazard ratio, 1.07; 95% confidence interval, 0.92‐1.25) between African Americans and Caucasians.

CONCLUSIONS.

The risk of mortality in patients with NHL was associated with socioeconomic status and was reduced in patients receiving chemotherapy. No significant differences in the risk of mortality were observed between African Americans and Caucasians after controlling for factors such as treatment and socioeconomic status. Cancer 2008. © 2008 American Cancer Society.  相似文献   

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Hepatitis C virus (HCV)-infection can cause hepatocellular carcinoma (HCC) and most likely non-Hodgkin lymphoma (NHL). No studies have compared the risk of these cancers between patients with chronic and cleared HCV-infection. The aim of this study was to estimate the 10-year risk of HCC and NHL in HCV-infected patients and to compare the risk of these cancers between HCV-infected patients and the general population in Denmark and between patients with chronic and cleared HCV-infection. Nationwide cohorts were used: 11,975 HCV-infected patients in the DANVIR cohort and 71,850 individuals from an age- and gender-matched general population cohort. Within DANVIR, 4,158 patients with chronic HCV-infection and 2,427 patients with cleared HCV-infection were studied. The 10-year risks of HCC and NHL in HCV-infected patients were 1.0% [95% confidence interval (CI): 0.8-1.3%] and 0.1% (95% CI: 0.1-0.2%), respectively. Compared to the general population, HCV-infected patients had a 62.91-fold increased risk of HCC (95% CI: 28.99-136.52), a 29.97-fold increased risk of NHL during the first year of follow-up (95% CI: 6.08-147.84), and a 1.26-fold increased risk of NHL after the first year (95% CI: 0.36-4.41). Chronic HCV-infection was associated with a 4.71-fold increased risk of HCC (95% CI: 1.67-13.32) compared to cleared HCV-infection; 5 and 0 events of NHL occurred in patients with chronic and cleared HCV-infection, respectively. HCC-risk is increased substantially in HCV-infected patients compared to the general population. Chronic as opposed to cleared HCV-infection increases the risk of HCC and perhaps NHL.  相似文献   

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High‐dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high‐dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high‐dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression‐free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F‐fluoro‐deoxy‐d ‐glucose positron emission tomography (18FDG‐PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow‐up of 45 months (range 1–164 months), 5‐year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F‐fluoro‐deoxy‐d ‐glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

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BACKGROUND: The current study was conducted to asses the safety profile and clinical activity of rituximab in combination with fludarabine and cyclophosphamide in patients with recurrent follicular lymphoma (FL). METHODS: This study was a noncomparative, multicenter, phase II study. Between March 2000 and December 2002, 54 patients with recurrent FL were enrolled in the FC+R trial. Patients received fludarabine at a dose of 25 mg/m(2) and cyclophosphamide at a dose of 300 mg/m(2) daily for 3 consecutive days, every 3 weeks for 4 cycles. Rituximab was administered at a dose of 375 mg/m(2) beginning 2 weeks after the first course of fludarabine and cyclophosphamide and then on Day 1 of each cycle thereafter. The planned treatment duration was 10 weeks. RESULTS: Overall, 92% of patients completed the planned therapy in 10 to 14 weeks and 74% achieved a complete response (CR). Among patients with BCL2-positive bone marrow, 86% obtained a molecular disease remission (MR). The median survival from treatment (SFT), the duration of disease remission (DR), and time to disease progression (TTP) had not been reached after a median follow-up of 45 months. Of the baseline characteristics, >2 previous treatments, BCL2-positive bone marrow, and low Follicular Lymphoma International Prognostic Index (FLIPI) score were found to be associated with better DR and/or TTP. Hematologic toxicity was transient and reversible, with the exception of 3 patients with severe and prolonged neutropenia. Three patients presented with infections, 1 of whom died of bronchopneumonia. CONCLUSIONS: The FC+R scheme, a nonanthracycline-containing regimen lasting up to 10 weeks, was found to be relatively well-tolerated and demonstrated significant antilymphoma activity with excellent clinical CR and molecular response rates.  相似文献   

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目的:观察大剂量化疗联合应用粒细胞集落刺激因子在没有干细胞支持情况下,治疗难治或复发性非霍奇金淋巴瘤(NHL)的疗效和不良反应。方法:采用大剂量化疗方案,DIAEM方案:异环磷酰胺1 500 mg/m2,静脉滴入,d1~d5;美斯纳800 mg/次,于异环磷酰胺后0、4和8 h静脉滴入,并同时水化;依托泊苷200 mg/m2,静脉滴入,d1~d5;表柔比星60 mg/m2,静脉滴入,d1。地塞米松20 mg,静脉滴入,d1~d5。ESHAP方案:顺铂25 mg/m2,静脉滴入,d1~d4;替尼泊苷(Vm-26)100 mg,静脉滴入,d1~d4;甲基泼尼松龙500 mg,静脉滴入,d1~d4;阿糖胞苷1 500 mg/m2,d5。两方案交替进行,粒细胞集落刺激因子5~10μg/(kg.d)于每周期化疗结束后24 h开始应用,至白细胞达2.0×109L-1且持续3 d停用。结果:大剂量化疗总有效率61.1%(22/36),其中CR12例(33.3%),PR10例(27.8%),SD 4例,PD 10例,1例于大剂量化疗后第7天死于颅内出血。主要不良反应为骨髓抑制,白细胞和血小板降到最低的中位时间分别为6和5 d,其恢复时间分别为10和12 d;27例(76.5%)出现发热性粒细胞减少,中位时间为6 d。结论:在无干细胞支持的情况下,采用大剂量化疗辅以粒细胞集落刺激因子支持是治疗难治或复发性NHL的有效措施。  相似文献   

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目的:观察吉西他滨(GEM)联合顺铂(DDP)、地塞米松(DXM)组成的GDP方案治疗复发性或难治性非霍奇金淋巴瘤(NHL)的疗效和毒副反应。方法:2005年10月~2007年1月我科收治的13例复发性或难治性NHL患者,分别为弥漫大B细胞淋巴瘤(BCEL-1)11例和外周T细胞淋巴瘤(TCEL-1)2例,给予吉西他滨1000mg/m^2,d1、d8,静脉滴注;顺铂25mg/m^2,d1~d3,静脉滴注;地塞米松20mg/d,d1~d5,口服。21天为1周期。2个周期后评价疗效,并随访疾病进展情况。结果:13例患者中,9例获缓解(69.2%),其中完全缓解4例(30.8%),部分缓解5例(38.5%)。在可随访评价的12例患者中位TTP7.9个月(95%CI:7.4~9.4个月)。毒副反应主要为骨髓抑制和轻中度的消化道反应。骨髓抑制表现为Ⅲ~Ⅳ度白细胞下降3例,Ⅲ度血小板下降4例。结论:吉西他滨联合顺铂、地塞米松组成的GDP方案治疗复发性或难治性NHL的近期疗效较好,安全性高。  相似文献   

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