Familial nodular lymphocyte predominant Hodgkin lymphoma: Successful treatment with CHOP plus rituximab

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare tumor type distinct from classical Hodgkin lymphoma and its familial form is unusual. The two cases (mother at age 48 and son at age 30 years) of NLPHL in advanced clinical stage are described. The patients were successfully treated with an immunochemotherapy schedule consisting CHOP plus rituximab (CHOP-R). This chemotherapy was well tolerated and the patients reached complete remission. These remissions were for 34 and 40 months for mother and son, respectively. In patients with NLPHL, CHOP-R regimen should be used as an alternative treatment regimen to obtain a good long-lasting response without any adverse events.     

Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma.

PURPOSE: Promising new therapeutic options for follicular lymphoma (FL) include fludarabine plus mitoxantrone (FM) and the mouse/human anti-CD20 antibody, rituximab. We performed a randomized comparative trial of FM with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) front-line chemotherapy with and without sequential rituximab. PATIENTS AND METHODS: All previously untreated CD20(+) FL patients presenting in 15 Italian cooperative institutions from October 1999 were randomly allocated to FM or CHOP. Following clinical or molecular restaging, patients in complete remission (CR) with bcl-2/IgH negativity (CR(-)) received no further treatment; those in CR with bcl-2/IgH positivity (CR(+)) received rituximab, as did those in partial remission (PR) with bcl-2/IgH negativity (PR(-)) or positivity (PR(+)); nonresponders (NR subgroup) were off study. RESULTS: After chemotherapy, the FM arm achieved higher rates of CR (68% [49 of 72 patients] v 42% [29 of 68 patients]; P =.003) and CR(-) (39% [28 of 72 patients] v 13 of 68 patients [19%]; P =.001). Rituximab elicited CR(-) in 55 of 95 treated patients (58%). The final CR(-) rate was higher in the FM arm (71% [51 of 72 patients] v 51% [35 of 68 patients]; P =.01). However, with a median follow-up of 19 months (range, 9 to 37 months), no statistically significant difference was found among the various study arms in terms of both progression-free (PFS) and overall survival (OS). CONCLUSION: These results indicate that FM is superior to CHOP for front-line treatment of FL and that rituximab is an effective sequential treatment option. However, they also confirm that this superiority is unlikely to translate into either better PFS or OS.     

利妥昔单抗联合CHOP与单用CHOP方案治疗初治弥漫大B细胞型淋巴瘤的对比研究

目的:比较利妥昔单抗(商品名:美罗华)联合CHOP(环磷酰胺,阿霉素,长春新碱和泼尼松)与单用CHOP方案化疗治疗弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的临床疗效。方法:根据患者的意愿,49例DLBCL患者分别接受6疗程CHOP方案或CHOP加利妥昔单抗方案化疗,每3周1疗程,共6个疗程。结果:R-CHOP组的CR率高于CHOP组,但差异无统计学意义(82.6%VS 65.4%,P=0.173)。中位随访时间为35月(4-66月),R-CHOP组及CHOP组的3年OS分别为75.0%±19.6%,54.9%±20.4%,P=0.043;而3年EFS分别为69.7%±20.9%,45.8%±20.6%,P=0.029。R-CHOP组的3年OS及EFS优于CHOP组,差异有统计学意义。两组患者的不良反应无明显差别。结论:与单用CHOP方案相比,利妥昔单抗联合CHOP方案明显提高DLBCL患者的EFS及OS,而不良反应无明显增加。     

利妥昔单抗联合CHOP与单用CHOP方案治疗初治弥漫大B细胞型淋巴瘤的对比研究

目的：比较利妥昔单抗（商品名：美罗华）联合CHOP（环磷酰胺,阿霉素,长春新碱和泼尼松）与单用CHOP方案化疗治疗弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma,DLBCL）的临床疗效。方法：根据患者的意愿,49例DLBCL患者分别接受6疗程CHOP方案或CHOP加利妥昔单抗方案化疗,每3周1疗程,共6个疗程。结果：R-CHOP组的CR率高于CHOP组,但差异无统计学意义（82.6%VS 65.4%,P=0.173）。中位随访时间为35月（4-66月）,R-CHOP组及CHOP组的3年OS分别为75.0%±19.6%,54.9%±20.4%,P=0.043;而3年EFS分别为69.7%±20.9%,45.8%±20.6%,P=0.029。R-CHOP组的3年OS及EFS优于CHOP组,差异有统计学意义。两组患者的不良反应无明显差别。结论：与单用CHOP方案相比,利妥昔单抗联合CHOP方案明显提高DLBCL患者的EFS及OS,而不良反应无明显增加。     

A case of pulmonary intravascular lymphoma treated with CHOP chemotherapy plus rituximab

We report a case of pulmonary intravascular lymphoma of large B cell type in a 72-year-old woman. She had a one-month history of fever and dry cough before admission. Chest X-ray revealed ground glass shadow in both lung fields, and the high-resolution CT disclosed centrilobular distribution of ground glass opacities. Transbronchial lung biopsy demonstrated large lymphoid cells in the capillaries of alveolar septa. The tumor cells showed strong immunohistochemical reactivity to CD 20. After combined treatment with CHOP and rituximab, clinical symptoms, laboratory and radiological findings were improved. As with diffuse large B cell lymphoma, CHOP chemotherapy plus rituximab may prove useful as a standard regimen for pulmonary intravascular lymphoma.     

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma

Background

The results of CHOP-21 (cyclophosphamide, doxorubicin, vincristine and prednisone given every 21 days) for the treatment of aggressive B-cell lymphoma have recently been improved by the addition of rituximab and by increasing the dose density. R-CHOP-14 combines these two approaches.

Patients and methods

We present our experience with R-CHOP-14 in a retrospective single-centre review of 50 patients consecutively treated for aggressive B-cell lymphoma.

Results

The median age was 59 years and 48% of patients were >60 years. Stage III–IV was present in 62% of the patients and international prognostic index was high-to-intermediate risk or high risk in 32% of the patients. Toxicity was mainly haematological, with grade 3–4 neutropenia observed in 32% and febrile neutropenia in 18%. Other relevant toxicities were peripheral neuropathy in 45% (grade 3 in 4%) and cardiac dysfunction grade 3 in 7.5%. After therapy, 82% of the patients achieved complete response or unproved complete response. With a median follow-up of 30 months, 3-year event-free survival and overall survival were 67% and 82% respectively.

Conclusions

In our experience the combination of R-CHOP-14 is highly effective in patients with aggressive B-cell lymphoma. However special attention must be paid to the control of early and late toxicities.     

美罗华联合CHOP方案与CHOP方案治疗初治弥漫性大B细胞淋巴瘤的临床对比研究

背景与目的:CHOP方案是治疗弥漫性大B细胞淋巴瘤的标准方案。美罗华是一种抗CD20单克隆抗体,对弥漫性大B细胞淋巴瘤有效。本研究中比较美罗华联合CHOP方案和单用CHOP方案治疗初治的弥漫性大B细胞淋巴瘤的疗效和不良反应。方法:采用同期非随机对照的前瞻性研究方法,将72例初治的弥漫性大B细胞淋巴瘤患者分为联合组和CHOP组。联合组34例,采用CHOP方案(环磷酰胺加阿霉素加长春新碱加强的松)加美罗华(375mg/m2,于每周期化疗前2天静脉滴注1次)治疗;CHOP组38例,单用CHOP方案化疗。两组均每3周为一个循环周期,6个周期后比较两组的疗效及不良反应。结果:联合组完全缓解23例,部分缓解7例,总有效率为93.8%(30/32);CHOP组完全缓解19例,部分缓解8例,总有效率为75.0%(27/36),两组疗效差异有显著性(P<0.05);联合组和CHOP组1年的无进展生存率分别为81.2%和52.8%,总生存率为93.8%和75.0%,联合组均显著优于CHOP组(P<0.05)。联合组的不良反应主要为发热等输注相关的不良反应,以及骨髓抑制等化疗相关的血液学不良反应,其中输注相关的不良反应轻微,患者均可耐受,而骨髓抑制情况与CHOP组类似。结论:美罗华联合CHOP方案能够提高CHOP方案治疗初治弥漫性大B细胞淋巴瘤的疗效,而毒性反应类似,可作为该病的一线治疗方案。     

Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy

BackgroundA recent laboratory study indicated that statins impaired the antitumor effects of rituximab by inducing conformational changes in CD20. Although these findings raised significant concerns about statin use during rituximab treatment, their clinical significance is unclear.Patients and methodsWe conducted a retrospective study investigating the effects of statins on the prognosis of diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Newly diagnosed DLBCL patients were analyzed (n = 256), including 35 patients taking statins.ResultsThe 3-year progression-free survival rates were 84% and 73% (P = 0.38), while the overall survival rates were 89% and 78% (P = 0.28) for those patients treated with and without statins, respectively. After adjusting for the International Prognostic Index and serum cholesterol level, statin use was not associated with prognosis.ConclusionsThese results indicate that statins do not influence the clinical prognosis of DLBCL treated with RCHOP. Further studies with larger numbers of patients are warranted to confirm the prognostic significance of statins for patients with DLBCL receiving rituximab-containing chemotherapy.     

Primary central nervous system lymphoma treated with rituximab plus temozolomide in a second line schedule

We report a case of primary CNS lymphoma treated with high-dose methotrexate in the first line. After disease progression the patient received cranial radiotherapy with concomitant temozolomide, followed by rituximab plus temozolomide, with complete remission of the disease maintained for at least two years and without major toxicity.     

替莫唑胺联合利妥昔单抗对复发的老年原发中枢神经淋巴瘤的应用

Objective: The aim of our study was to analyze the long-term results of rituximab combined with temozolomide in treatment of elderly patients (> 60 years) with relapsed primary central nervous system lymphoma (PCNSL). Methods: Twelve postoperative elderly patients (> 60 years) were treated between August 2004 and October 2009. Temozolomide 100 mg/m2 to 200 mg/m2 days 1 to 7 and 15 to 21 and rituximab 375 mg/m2 days 1, 5, 8, 22. The maximum number of rituximab cycles was two. After one or two cycles of this ...     

MIB‐1 labeling index as a prognostic factor for patients with follicular lymphoma treated with rituximab plus CHOP therapy

The MIB‐1 labeling index, which is based on Ki67 immunostaining, is widely used to evaluate the proliferation of tumor cells in lymphoma. However, its clinical significance has not been fully assessed. We retrospectively evaluated the prognostic impact of the MIB‐1 labeling index at the time of diagnosis, in 98 patients with follicular lymphoma (FL) grade 1–3b who were treated uniformly with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R‐CHOP) therapy. The 5‐year progression‐free survival (PFS) for an MIB‐1 labeling index of ≥10% (n = 60) and <10% (n = 38) was 35% and 61%, respectively (P = 0.015). The 5‐year overall survival (OS) for an MIB‐1 labeling index of ≥10% and <10% was 77% and 92%, respectively (P = 0.025). Pathological grading was not correlated with PFS or OS. In multivariate analysis, an MIB‐1 labeling index of ≥10% was independently associated with poor PFS and OS. In conclusion, an MIB‐1 labeling index of 10% is a useful cut‐off level for predicting the prognosis of patients with FL.     

CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma.

PURPOSE: To investigate whether the relative dose-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients aged 65 to 90 years (median, 72 years) with stage II to IV aggressive NHL were randomly assigned to receive standard CHOP every 3 weeks or CHOP plus G-CSF every 3 weeks on days 2 to 11 of each cycle. RESULTS: In 389 eligible patients, the relative dose intensities (RDIs) of cyclophosphamide (median, 96.3% v 93.9%; P =.01) and doxorubicin (median, 95.4% v 93.3%; P =.04) were higher in patients treated with CHOP plus G-CSF. The complete response rates were 55% and 52% for CHOP and CHOP plus G-CSF, respectively (P =.63). The actuarial overall survival at 5 years was 22% with CHOP alone, compared with 24% with CHOP plus G-CSF (P =.76), with a median follow-up of 33 months. Patients treated with CHOP plus G-CSF had an identical incidence of infections, with World Health Organization grade 3 to 4 (34 of 1,191 cycles v 36 of 1,195 cycles). Only the cumulative days with antibiotics were fewer with CHOP plus G-CSF (median, 0 v 6 days; P =.006) than with CHOP alone. The number of hospital admissions and the number of days in hospital were not different. CONCLUSION: In elderly patients, G-CSF improved the RDI of CHOP, but this did not lead to a higher complete response rate or better overall survival. G-CSF did not prevent serious infections.     

利妥昔单抗联合CHOP方案治疗B细胞非霍奇金淋巴瘤的疗效分析

目的：探讨利妥昔单抗联合CHOP方案治疗B细胞型非霍奇金淋巴瘤（NHL）的临床效果和不良反应。方法选择96例CD20阳性的B细胞NHL患者分为研究组49例和对照组47例,研究组采用利妥昔单抗与CHOP方案联合治疗方案,对照组只采用CHOP化疗方案。应用4个疗程后评价两组疗效及不良反应。结果研究组治疗有效率为90.0%,高于对照组的72.3%,差异有统计学意义（P﹤0.05）。而且两组的白细胞下降、脱发、恶心呕吐、便秘、血小板减少、贫血、肺部感染等不良反应比较,差异无统计学意义（P﹥0.05）。研究组1年、3年、5年无进展生存率（PFS）分别为81.6%、61.2%、26.5%,生存率分别为89.8%、65.3%、30.6%,均高于对照组,差异均有统计学意义（P﹤0.05）。结论采用利妥昔单抗与CHOP联合方案治疗B细胞非霍奇金淋巴瘤,可以提高临床疗效和远期生存率,且不因联合化疗而增加不良反应。     

Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia.

PURPOSE: For more than two decades, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the standard therapy for diffuse large B-cell lymphoma (DLBCL). The addition of rituximab to CHOP has been shown to improve outcome in elderly patients with DLBCL. We conducted a population-based analysis to assess the impact of this combination therapy on adult patients with DLBCL in the province of British Columbia (BC). METHODS: We compared outcomes during a 3-year period; 18 months before (prerituximab) and 18 months after (postrituximab) institution of a policy recommending the combination of CHOP and rituximab for all patients with newly diagnosed advanced-stage (stage III or IV or stage I or II with "B" symptoms or bulky [> 10 cm] disease) DLBCL. RESULTS: A total of 292 patients were evaluated; 140 in the prerituximab group (median follow-up, 42 months) and 152 in the postrituximab group (median follow-up, 24 months). Both progression-free survival (risk ratio, 0.56; 95% CI, 0.39 to 0.81; P = .002) and overall survival (risk ratio, 0.40; 95% CI, 0.27 to 0.61, P < .0001) were significantly improved in the postrituximab group. After controlling for age and International Prognostic Index score, era of treatment remained a strong independent predictor of progression-free survival (risk ratio, 0.59; 95% CI, 0.41 to 0.85; P = .005) and overall survival (risk ratio, 0.43; 95% CI, 0.29 to 0.66; P < .001). The benefit of treatment in the postrituximab era was present regardless of age. CONCLUSION: The addition of rituximab to CHOP chemotherapy has resulted in a dramatic improvement in outcome for DLBCL patients of all ages in the province of BC.     

利妥昔单抗联合CHOP方案治疗B细胞非霍奇金淋巴瘤的疗效观察

目的探讨利妥昔单抗联合环磷酰胺+多柔比星+长春新碱+泼尼松(CHOP方案)治疗B细胞非霍奇金淋巴瘤的疗效及安全性。方法选取2018年10月至2020年12月间湘乡市人民医院收治的76例B细胞非霍奇金淋巴瘤患者,采用单双号抽签方式分为观察组和对照组,每组38例。对照组患者采用常规CHOP方案治疗,观察组患者采用利妥昔单抗联合CHOP方案治疗,比较两组患者疾病控制情况、远期生存率及治疗期间不良反应。结果观察组患者治疗有效率为86.8%,高于对照组的65.8%,差异有统计学意义(P <0.05)。观察组患者1年和3年无进展生存时间(PFS)和总生存时间(OS)均高于对照组,差异均有统计学意义(均P <0.05);观察组患者5年PFS和OS均高于对照组,但差异无统计学意义(P> 0.05)。两组患者白细胞下降、血小板减少、恶心呕吐、脱发及贫血等不良反应发生率比较,差异无统计学意义(P> 0.05)。结论 B细胞非霍奇金淋巴瘤患者采用利妥昔单抗联合CHOP方案治疗,近期效果较好,可提高远期生存率,且不增加不良反应,临床值得推广。     

High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine.

PURPOSE: To determine the response, failure-free survival (FFS), and overall survival rates and toxicity of rituximab plus an intense chemotherapy regimen in patients with previously untreated aggressive mantle-cell lymphoma (MCL). PATIENTS AND METHODS: This was a prospective phase II trial of rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD; considered one cycle) alternating every 21 days with rituximab plus high-dose methotrexate-cytarabine (considered one cycle) for a total of six to eight cycles. RESULTS: Of 97 assessable patients, 97% responded, and 87% achieved a complete response (CR) or unconfirmed CR. With a median follow-up time of 40 months, the 3-year FFS and overall survival rates were 64% and 82%, respectively, without a plateau in the curves. For the subgroup of patients < or = 65 years of age, the 3-year FFS rate was 73%. The principal toxicity was hematologic. Five patients died from acute toxicity. Four patients developed treatment-related myelodysplasia/acute myelogenous leukemia, and three patients died while in remission from MCL. A total of eight treatment-related deaths (8%) occurred. CONCLUSION: Rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine is effective in untreated aggressive MCL. Toxicity is significant but expected. Because of the shorter FFS concurrent with significant toxicity in patients more than 65 years of age, this regimen is not recommended as standard therapy for this age subgroup. Larger prospective randomized studies are needed to define the role of this regimen in the treatment of MCL patients compared with existing and new treatment modalities.     

Reactivation of hepatitis B virus due to rituximab plus CHOP after preemptive lamivudine administration in a patient with diffuse large B-cell lymphoma

A 59-year-old woman received eight cycles of R-CHOP for diffuse large B-cell lymphoma from July, 2004. Pretreatment HBV serological tests were positive, however, the transaminases were within normal limits, and she remained asymptomatic. Lamivudine (LAM) was administered orally from the start of R-CHOP. HBV-DNA levels gradually decreased and were not detected until December, 2004. LAM was administered until 3 months after the end of chemotherapy, with the entire treatment lasting less than 1 year. Two months after the cessation of treatment, she was re-admitted for general malaise. A liver function test revealed severe abnormalities, and HBVDNA levels were increased. Clinically, she was experiencing acute hepatitis due to HBV reactivation. She was then treated with LAM and interferon-beta immediately. Her HBV-DNA levels soon decreased, and liver function improved.     

Rapid-infusion rituximab in lymphoma treatment.

Rituximab® (MabThera; Rituxan Roche) is a chimeric human/murineimmunoglobulin G1 monoclonal antibody that binds specificallyto the B-cell-surface antigen, CD20. Using the combination ofCHOP-R leads to significant improvement in the outcome of elderlypatients with diffuse large B-cell lymphoma, with significantsurvival benefits maintained during a 5-year follow-up [1]. Other studies have been conducted in patients with follicularlymphoma or mantle-cell lymphoma and have shown the same benefitsfor the combination of rituximab plus chemotherapy [2]. In general, rituximab is a well-tolerated medicine, althougha specific infusion rate