美罗华联合CHOP方案治疗B细胞性非霍奇金淋巴瘤效果观察

［摘要］　目的　探讨美罗华联合CHOP方案治疗B细胞性非霍奇金淋巴瘤的临床效果及不良反应。方法　选择B细胞性非霍奇金淋巴瘤60例随机分成观察组和对照组各30例。观察组采用美罗华联合CHOP方案治疗,对照组仅采用CHOP方案治疗,比较两组临床疗效及不良反应情况。结果　观察组患者临床疗效明显优于对照组(P<0.05);不良反应除发热例数多于对照组外（P<0.05）,其余两组比较差异无统计学意义（P>0.05）。结论　对B细胞性非霍奇金淋巴瘤患者采用美罗华联合CHOP方案治疗,能够有效提高患者的临床疗效,值得临床推广。     

美罗华联合化疗治疗B细胞性非霍奇金淋巴瘤11例

非霍奇金淋巴瘤（NHL）为起源于淋巴结或淋巴组织的恶性肿瘤,B细胞来源的NHL。美罗华（Rituximab）是第一个获得FDA批准用于临床的人鼠嵌合型抗CD20单抗,能与B细胞表面CD20抗原特异性结合,通过诱导抗体介导细胞毒性作用和补体介导的细胞毒性作用,诱导细胞凋亡,因而通过多种机制清除体内B细胞,达到治疗肿瘤的目的。我院2001年8月-2008年2月应用美罗华联合化疗治疗NHL患者共11例,取得较好疗效,现报告如下。     

美罗华加沙利度胺联合化疗治疗侵袭性B细胞非霍奇金淋巴瘤的疗效分析

目的：评价美罗华联合沙利度胺化疗治疗侵袭性B-细胞非霍奇金淋巴瘤的临床疗效。方法：采用前瞻性对照分析,对60例侵袭性B-细胞非霍奇金淋巴瘤患者随机分成2组,即美罗华＋CHOP组（对照组）和美罗华＋CHOP＋反应停组（观察组）,比较2组患者的总有效率,总生存及无进展生存。结果：观察组：CR28例（80%）,PR5例（14.3%）,总有效率（CR＋PR）94.3%。对照组：CR25例（72%）,PR3例（12%）,总有效率（CR＋PR）84%。2组有显著差异（P〈0.05）。总生存：观察组：35例患者1年、2年、3年OS率分别为91.4%（32/35）,85.7%（30/35）,74.3%（26/35）;对照组：25例患者1年、2年、3年OS率分别为84%（21/25）,64%（16/25）,52%（13/25）,2组有显著差异（P〈0.05）。无进展生存率比较：观察组：35例患者1年、2年、3年PFS率分别为88.6%（31/35）,71.4%（25/35）,57%（20/35）;对照组：25例患者1年、2年、3年PFS率分别为68%（17/25）,52%（13/25）,36%（9/25）,2组有显著差异（P〈0.05）。而且不良反应轻。结论：美罗华联合反应停化疗治疗侵袭性B-NHL疗效显著,不良反应轻,值得临床推荐。     

美罗华联合CHOP方案治疗复发性非霍奇金淋巴瘤疗效观察

将21例复发性B细胞非霍奇金淋巴瘤（NHL）患者随机分为两组,观察组予美罗华联合CHOP方案治疗,对照组予CHOP方案联合博莱霉素、依托泊苷或卡氮芥治疗,每周期21 d,治疗4-6个周期。结果与对照组比较,观察组总有效率明显提高（P〈0.05）,平均无进展生存期明显延长（P〈0.05）,且无严重并发症。认为美罗华联合CHOP方案治疗复发性NHL缓解率高,毒副作用较小。     

美罗华联合化疗治疗B细胞非霍奇金淋巴瘤10例疗效观察

目的:观察美罗华联合化疗治疗B细胞非霍奇金淋巴瘤(NHL)的临床疗效。方法:10例经病理证实CD20 的B细胞NHL患者,使用美罗华375 mg／m2,静脉滴注,每周1次,共4周为1个疗程,同时使用化疗药物。结果:10例患者经治疗后完全缓解8例,部分缓解2例,1例出现过敏反应。结论:美罗华联合化疗治疗CD20 B细胞NHL是一种有效的治疗方案,无明显不良反应。     

美罗华联合化疗治疗B细胞非霍奇金淋巴瘤的临床分析

目的:了解美罗华联合化疗治疗CD20阳性B细胞非霍奇金淋巴瘤的临床疗效及安全性。方法:美罗华375mg/m2于每周期化疗前1d静脉滴注,每3周为1个循环周期;4~6个周期后评价疗效及不良反应。结果:7例初治患者,完全缓解(CR)5例,部分缓解(PR)2例。3例复发或难治患者,2例达CR,1例PR。主要的不良反应为发热等输注相关的不良反应,以及化疗相关的血液学毒性,患者均可耐受。仅1例出现爆发性肝衰竭。结论:美罗华是一种高效、安全治疗B细胞淋巴瘤的药物,但其用药最佳方案、长期疗效以及不良反应仍待临床观察探讨。     

美罗华联合化疗治疗B细胞非霍奇金淋巴瘤的临床分析

目的了解美罗华联合化疗治疗CD20阳性B细胞非霍奇金淋巴瘤的临床疗效及安全性.方法美罗华375 mg/m2于每周期化疗前1 d静脉滴注,每3周为1个循环周期;4～6个周期后评价疗效及不良反应.结果7例初治患者,完全缓解(CR)5例,部分缓解(PR)2例.3例复发或难治患者,2例达CR,1例PR.主要的不良反应为发热等输注相关的不良反应,以及化疗相关的血液学毒性,患者均可耐受.仅1例出现爆发性肝衰竭.结论美罗华是一种高效、安全治疗B细胞淋巴瘤的药物,但其用药最佳方案、长期疗效以及不良反应仍待临床观察探讨.     

复发难治B细胞性非霍奇金淋巴瘤的治疗进展

迄今为止,仍有约50%的非霍奇金淋巴瘤(NHL)患者初治耐药或缓解后复发而不能治愈。因此,复发难治NHL已成为临床迫切需要解决的难点问题之一。NHL中以B细胞性淋巴瘤为主(超过70%),包括弥漫大B细胞淋巴瘤、套细胞淋巴瘤、滤泡型淋巴瘤等类型。现结合文献对复发难治B     

美罗华治疗难治性非霍奇金淋巴瘤3例

非霍奇金淋巴瘤(NHL)是最常见的淋巴系统恶性肿瘤，其中绝大多数来源于B细胞，90％的病例表达CD20抗原。常规化疗、放疗难以延长NHL患者生存期，且复发率高，治愈率低。近年来针对B细胞CD20抗原研制的特异性单抗美罗华，用于治疗B细胞淋巴瘤，能导致B细胞溶解，并能抑制其增殖，诱导凋亡和提高肿瘤化疗的敏感性。据国内外临床证明，对B细胞淋巴瘤有肯定疗效。现将我科应用美罗华治疗的3例难治性NHL报告如下。     

Impact of treatment-related toxicity on outcome of HCV-positive diffuse large B-cell lymphoma in rituximab era

Novelty and Impact

This first study compares the survival of HCV-positive DLBCL treated with and without rituximab which showed in toxicity and the outcome.

Background

The effect of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era is unclear. The treatment and the outcome of patients with DLBCL and HCV infection are still a matter of debate.

Methods

We analyzed 137 DLBCL patients positive to HCV, treated with chemotherapy regimens include cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab. Survival outcomes and hepatic toxicity were compared in DLBCL patients positive to HCV infection according to CHOP ± rituximab.

Result

Our result showed that the group of patients treated with R-CHOP has significant high incidence of hepatic toxicity grade (3–4) (28 vs. 18%, P value 0.001) and worse progression-free survival (55 vs. 80%, P value 0.002) in comparison with the group treated with CHOP, and also there is significant difference between both groups in overall survival. This first study compares the survival of HCV-positive DLBCL treated with and without rituximab which showed significant differences.

Conclusion

We conclude that HCV-positive patients with DLBCL treated with rituximab plus CHOP have high incidence in hepatic toxicity. Speci?c protocols evaluating antiviral therapy should be designed for these patients     

Cost-effectiveness of rituximab (MabThera) in diffuse large B-cell lymphoma in The Netherlands

OBJECTIVE: To determine the incremental cost-effectiveness ratio (ICER) of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) vs. CHOP plus rituximab (R-CHOP) in diffuse large B-cell lymphoma (DLBCL) patients in the Netherlands. METHODS: A state transition model was developed to estimate the clinical course, costs and quality of life of patients with stage II, III or IV DLBCL receiving initial treatment with CHOP or R-CHOP to arrive at the ICER. The base year for the cost analysis was 2002 and was performed from the societal perspective. Only direct medical costs were included. The time horizon of the model was 15 yr and both costs and effects were discounted at 4%. Sensitivity analyses were performed to determine the effect of varying base-line assumptions of the model. RESULTS: The incremental gain in quality adjusted life years (QALYs) was 0.88 in both the younger and the older patient groups. The costs were 12 343 higher in the younger group of patients and 15 860 in the older patients. This resulted in an ICER of 13 983 for the younger and 17 933 for the older patients per QALY gained. These results were sensitive to the time horizon of the model, other variations had a marginal impact on the outcome. CONCLUSION: The addition of rituximab to standard therapy for DLBCL results in a gain of 0.88 QALYs. The ICER of 13 983 for younger and 17 933 for older patients per QALY gained should, seen in the light of disease severity, be considered acceptable by most policy makers in priority setting for budget allocation.     

Successful rituximab-CHOP treatment of systemic lupus erythematosus associated with diffuse large B-cell non-Hodgkin lymphoma

The authors discuss the case of a 76-year-old female patient who has been suffering from subacute cutaneous lupus erythematosus since 1983. In 1999 she was diagnosed with systemic lupus erythematosus (SLE) based on her symptoms of malar rash, polyarthritis, leukopenia, autoimmune hemolytic anemia and positive anti-DNA antibody test. For this she received methylprednisolone and cyclophosphamide. After 3 years of remission, symptoms of cutaneous vasculitis appeared in 2004, which transitionally responded to treatment with azathioprin and methylprednisolone. Her cutaneous symptoms, however, progressed quickly along with generalized lymphadenopathy, splenomegaly and thrombocytopenia. Immunohistological evaluation of the lymph node biopsy showed diffuse large B-cell lymphoma. She developed complete remission after treatment with six-cycle R-CHOP (rituximab, and reduced doses of cyclophosphamide, vincristin, adriablastin, methylprednisolone). SLE became inactive and her symptoms of vasculitis resolved. The authors are bringing attention to one of the possible late complications of systemic lupus, and also underscoring that treatment with rituximab (+CHOP) was beneficial not only for the lymphoma but the SLE as well.     

VNCOP-B plus rituximab therapy in elderly patients with aggressive B-cell non-Hodgkin lymphoma: A multicenter experience

CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) plus rituximab is a standard chemotherapy used to treat patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). However, among elderly patients, this regimen has not been completely satisfactory in its efficacy and safety. We report our clinical experience in 8 collaborative institutions to determine if the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone, and bleomycin) combination therapy plus rituximab was effective and safe to treat elderly patients with aggressive B-NHL. Between September 2004 and December 2007, 23 previously untreated patients, median age 73 years, 50.0% classified as high-intermediate/high-risk on the standard International Prognostic Index (IPI) entered this trial. Complete remission rate was 90.5%, with a 100% overall response rate (RR) at the end of induction therapy; overall survival (OS) rate at 3 years was 76.4% (median follow-up 744 days), with an 82.6% 3-year progression-free survival (PFS) rate (median follow-up 744 days). The most common grade 3/4 toxicities were hematologic, including neutropenia in 75.0% of the patients despite prophylactic administration of granulocyte colony-stimulating factor (G-CSF), febrile neutropenia in 30.0%, respectively. There was no treatment-related mortality (TRM). Rituximab not only combined with chemotherapy but also given sequentially improved survival. R-VNCOP-B could be another option for elderly patients who are not considered to tolerate in receiving R-CHOP.     

Cytomegalovirus enterocolitis in a patient with diffuse large B-cell lymphoma after chemotherapy with rituximab

TO THE EDITOR In response to Unluturk et al ’s letter to the editor entitled ‘Cytomegalovirus gastritis after rituximab treatment in a non-Hodgkin’s lymphoma patient[1], a similar case of cy- tomegalovirus (CMV) enterocolitis after treatment with ritux…     

Recent developments in the treatment of aggressive non-Hodgkin lymphoma

SUMMARY: Options for treating aggressive non-Hodgkin lymphoma (NHL) have expanded in recent years. In phase 3 clinical trials, giving rituximab with cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) every 3 weeks (R-CHOP-21) has been associated with improved survival, without increased toxicity, in all patient groups studied. Giving dose-dense CHOP--CHOP every 2 weeks (CHOP-14)--has also proved appropriate for all patients 18-75 years old. Studies combining these approaches--dose-dense CHOP with rituximab (R-CHOP-14)--have shown improved survival over CHOP-14 in patients 60-81 years old. These results also indicate the importance of delivering chemotherapy at full dose and on schedule, which can improve survival in aggressive NHL. Effective delivery of dose-dense regimens requires granulocyte colony-stimulating factor support, which should also be considered for standard CHOP. A key question for the future is whether R-CHOP-14 is superior to R-CHOP-21.     

Achievement of optimal average relative dose intensity and correlation with survival in diffuse large B-cell lymphoma patients treated with CHOP

The treatment of diffuse large B-cell lymphoma with chemotherapy was retrospectively evaluated in 348 patients who had received at least three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like, ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone)-like or CHVmP-BV (cyclophosphamide, hydroxorubicin, Vm-26, prednisone, vincristine and bleomycin) treatment in Belgium between 1995 and 2000. In our sample, the proportion who received each of the three regimens was 78.4, 16.4, and 5.2%, respectively. Of those prescribed CHOP-like regimens, 15% received <80% average relative dose intensity (ARDI). In 210 patients treated with CHOP-21 (77% of the CHOP-like group), median survival was 7.08 years in those who received >90% of the ARDI, significantly longer than in those who received ≤;90% of the ARDI (p = 0.002). Dose reductions and/or delays, mainly due to hematological toxicities, resulted in a reduction in treatment intensity. These data indicate that patient outcome is improved when the intensity of chemotherapy treatment is optimal. See Appendix for a list of participating centers and physicians.     

Lack of prognostic significance of the germinal-center phenotype in diffuse large B-cell lymphoma patients treated with CHOP-like chemotherapy with and without rituximab

The influence of the germinal-center B-cell (GCB) and the non-GCB phenotypes of diffuse large B-cell lymphoma (DLBCL) on the outcome of 92 patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like chemotherapy, with or without rituximab was determined in this study. The differentiation between the GCB and non-GCB types was arrived at by immunohistochemistry using previously published criteria. Thirty-nine patients had the GCB and 53 had the non-GCB type of DLBCL. Forty-nine patients were treated with rituximab and chemotherapy; 43 were treated with chemotherapy alone. The GCB and non-GCB group did not differ in their international prognostic index factors and score, presence of bulky disease, or frequency of rituximab treatment. Median follow-up of the surviving patients was carried out for 37 months. There was no difference between the GCB and non-GCB groups in both overall response rates (67 vs. 70%, respectively) and estimated rates of 3-year event-free (46 vs. 49%, respectively) and overall (54 vs. 56%, respectively) survival. In addition, no differences of the outcomes were observed between the subgroups treated with or without rituximab. The patients of this study with immunohistochemically determined GCB-type DLBCL did not have an improved prognosis, irrespective of whether they had received rituximab or not.     

Risk factors for late-onset neutropenia after rituximab treatment of B-cell lymphoma

Abstract

Objectives

Late-onset neutropenia after rituximab (RTX) therapy (R-LON) has been widely reported, but clinical studies on a large number of cases are limited. In this study, we aimed to investigate the incidence and risk factors of R-LON.

Patients and methods

In this study, we retrospectively analyzed data of 213 enrolled B-cell lymphoma patients (male 114; female 99) treated with RTX at a single institution. R-LON was defined as otherwise unexplained grade III–IV neutropenia after RTX. The median age of the patients was 62 years, and 129 of them were initially diagnosed at advanced stages (stage III–IV).

Results

R-LON occurred in 19 patients within a median of 121 (range, 49–474) days after the last RTX administration. The 1-year cumulative incidence was 9.0%. On univariate analysis, older age (>60 years), advanced stage, and purine analog or methotrexate administration were significant or borderline significant risk factors for R-LON, whereas sex, disease type, bone marrow invasion, combination with cytotoxic chemotherapeutic drugs, intensified therapy (compared with R-CHOP), prior autologous transplantation, and repeated RTX administration were not. On multivariate analysis, older age (hazard ratio (HR), 2.95) and advanced stage (HR, 3.56) were significant risk factors. Treatment with granulocyte colony-stimulating factor was feasible in grade IV R-LON patients with high risk of infection.

Discussion and conclusion

Careful follow-up is therefore necessary after B-cell lymphoma treatment, especially in high-risk patients with advanced disease or of older age.