利妥昔单抗联合沙利度胺维持治疗老年弥漫大B细胞淋巴瘤的疗效评价

目的评价利妥昔单抗联合沙利度胺维持治疗老年弥漫大B细胞淋巴瘤(Diffuse large B cell lymphoma,DLBCL)的有效性及安全性。方法回顾性分析甘肃省武威肿瘤医院血液科使用R-CHOP方案化疗后完全缓解的≥60岁的DLBCL患者86例,按其治疗方案分为2组。对照组患者在完全缓解后单用利妥昔单抗维持治疗(n=43);治疗组患者应用利妥昔单抗联合沙利度胺方案维持治疗(n=43例)。对两组患者的预后进行分析。结果治疗组4年、5年总生存期(OS)率高于对照组(P<0.01);3年、4年、5年无进展生存期(PFS)率高于对照组(P<0.01);治疗组总生存时间、无进展生存时间明显长于对照组(P<0.001)。结论利妥昔单抗联合沙利度胺维持治疗老年人DLBCL,可延长患者总生存时间及无进展生存时间,无严重不良反应发生。     

美罗华联合CHOP治疗B细胞性非霍奇金淋巴瘤

目的评价美罗华(Rituximah)联合CHOP(R-CHOP)方案治疗CD20阳性B细胞性非霍奇金淋巴瘤(NHL)的临床疗效及不良反应。方法将60例初治B细胞淋巴瘤患者分为R-CHOP组和CHOP组各30例。R-CHOP组采用R-CHOP方案化疗;CHOP组采用CHOP方案化疗。6个疗程后比较两组的临床疗效及不良反应。结果 R-CHOP组完全缓解率达80%,总有效率90%;CHOP组完全缓解率为60%,总有效率为73.3%,两组疗效差异有统计学意义(P<0.01)。两组不良反应差异无统计学意义(P>0.05)。结论美罗华联合CHOP方案治疗CD20阳性B细胞性非霍奇金淋巴瘤疗效显著,不良反应与单纯化疗相似,可作为该病目前的首选方案。     

Biweekly CHOP therapy improves therapeutic effect in the non-GCB subtype of diffuse large B-cell lymphoma

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is accepted as the best available standard treatment for diffuse large B-cell lymphoma (DLBCL) patients; however, the therapeutic efficacy seems unsatisfactory. Additional rituximab will improve the cure rate, but it is not popular in China because of its increased medical cost. Germinal center B-cell (GCB) and non-GCB subtypes distinction have been described as independent prognostic factors, and provides likelihood for cure with chemotherapy. The aim of the study is to explore the association between Immunophenotype and treatment regimen. Between August 2003 and May 2006, 66 patients with DLBCL were enrolled, according to immunohistochemistry results (GCB and non-GCB phenotype), randomly assigned to receive either six to eight cycles of CHOP every 2 weeks or standard CHOP every 3 weeks. After a median follow-up duration of 32 months (range of 4 to 42 months), an estimated 3-year overall survival (OS) rate for the GCB patients were 68.2% and 55.6% for the biweekly CHOP regimen and standard CHOP regimen respectively, while the data were 62.8% and 37.9% respectively for the non-GCB cases. The biweekly CHOP therapy showed higher efficacy than standard treatment, and its superiority was more obvious with the non-GCB subgroup. All rights reserved.     

Aggressive lymphoma: improving treatment outcome with rituximab

The standard therapy for patients with aggressive lymphoma is cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, which achieves a complete response in more than 60% of patients but is curative in only about 40-50%. More aggressive and/or dose-intensified chemotherapy regimens have failed to provide significant survival advantages compared with CHOP, and may have higher toxicity. Rituximab, a chimeric monoclonal antibody to the CD20 antigen, is effective as monotherapy in aggressive lymphoma and in combination with chemotherapy has demonstrated high response rates in phase II trials. A scheduled interim analysis of a randomized, prospective trial comparing rituximab plus CHOP with CHOP alone in elderly patients with untreated diffuse large B-cell lymphoma has shown significantly better response rates and survival with rituximab plus CHOP compared with CHOP alone. These results represent the first significant improvement in overall survival over CHOP in aggressive lymphoma for over 20 years. The addition of rituximab was not associated with significant additional toxicity over that seen with CHOP alone. Ongoing studies are underway to establish whether the survival benefit of rituximab plus CHOP is seen in younger patient populations. Rituximab in combination with chemotherapy is also being evaluated as salvage treatment for patients who relapse after initial chemotherapy. In a preliminary analysis of a study in 50 patients with refractory or relapsed aggressive lymphoma, rituximab plus etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH) chemotherapy has demonstrated promising results when used as sole salvage therapy and as an induction therapy prior to autologous stem-cell transplantation, again without significant additional toxicity.     

R-CHOP和CHOP方案治疗早期原发性胃弥漫大B细胞淋巴瘤的疗效和毒性比较

目的探讨R-CHOP方案治疗早期原发性胃弥漫大B细胞淋巴瘤的临床疗效及不良反应。方法回顾性分析和比较采用R-CHOP方案（16例）以及CHOP方案（16例）治疗的初治早期（Ⅰ～Ⅱ期）胃弥漫大B细胞淋巴瘤患者的近期疗效及不良反应。结果 R-CHOP组患者化疗后CR8例,PR6例,SD1例,PD1例,有效率为87.5%（14/16）;CHOP组患者化疗后CR6例,PR5例,SD2例,PD3例,有效率为68.7%（11/16）,R-CHOP组有效率高于CHOP组（P〈0.05）。两组的不良反应主要为骨髓抑制、感染、粘膜炎、胃肠道反应、发热、肝功能损害。神经毒性及过敏反应等,经对症治疗后都能较快缓解,两组的不良反应发生率差异无统计学意义。结论 R-CHOP方案治疗早期胃弥漫大B细胞淋巴瘤的临床疗效优于CHOP方案,不良反应无明显差异。     

弥漫大B细胞淋巴瘤治疗的研究进展

弥漫大B细胞淋巴瘤（DLBCL）属于侵袭性B细胞淋巴瘤,目前利妥昔单抗联合环磷酰胺+蒽环类+长春碱类+糖皮质激素（R-CHOP方案）已成为治疗DLBCL的一线治疗方案,但部分患者存在复发或疾病进展情况,针对这类患者的治疗仍是目前临床研究关注的重点。目前针对复发/难治DLBCL患者的治疗主要有抗体药物偶联物、靶向药物、免疫检查点抑制剂、细胞免疫治疗及造血干细胞移植等,有望为患者的疾病预后带来显著改善。     

美罗华联合化疗治疗B细胞非霍奇金淋巴瘤46例临床分析

目的 探讨美罗华联合化疗治疗B细胞非霍奇金淋巴瘤的临床疗效.方法 选择2004年1月-2009年11月收治于我院的B细胞非霍奇金淋巴瘤患者92例.随机分为观察组(46例)和对照组(46例),观察组采用美罗华联合CHOP化疗治疗,对照组采用单纯CHOP方案化疗,比较两组治疗效果.结果 观察组总有效率89.1%,对照组总有效率88.7%,比较差异有显著性(P<0.05);观察组不良反应7例,对照组发生8例,比较差异无显著性(P>0.05).结论 美罗华联合化疗治疗B细胞非霍奇金淋巴瘤,具有临床疗效好、不良反应少、生存率高等优点.值得推广应用.     

美罗华联合化疗治疗B细胞非霍奇金淋巴瘤46例临床分析

目的 探讨美罗华联合化疗治疗B细胞非霍奇金淋巴瘤的临床疗效.方法 选择2004年1月-2009年11月收治于我院的B细胞非霍奇金淋巴瘤患者92例.随机分为观察组(46例)和对照组(46例),观察组采用美罗华联合CHOP化疗治疗,对照组采用单纯CHOP方案化疗,比较两组治疗效果.结果 观察组总有效率89.1%,对照组总有效率88.7%,比较差异有显著性(P<0.05);观察组不良反应7例,对照组发生8例,比较差异无显著性(P>0.05).结论 美罗华联合化疗治疗B细胞非霍奇金淋巴瘤,具有临床疗效好、不良反应少、生存率高等优点.值得推广应用.     

美罗华联合化疗治疗B细胞非霍奇金淋巴瘤46例临床分析

目的探讨美罗华联合化疗治疗B细胞非霍奇金淋巴瘤的临床疗效。方法选择2004年1月-2009年11月收治于我院的B细胞非霍奇金淋巴瘤患者92例,随机分为观察组（46例）和对照组（46例）,观察组采用美罗华联合CHOP化疗治疗,对照组采用单纯CHOP方案化疗,比较两组治疗效果。结果观察组总有效率89．1％,对照组总有效率88．7％,比较差异有显著性（P〈0．05）;观察组不良反应7例,对照组发生8例,比较差异无显著性（P〉0．05）。结论美罗华联合化疗治疗B细胞非霍奇金淋巴瘤,具有临床疗效好、不良反应少、生存率高等优点,值得推广应用。     

利妥昔单抗联合化疗治疗弥漫性大B细胞淋巴瘤的临床观察

目的：评价利妥昔单抗联合化疗治疗弥漫性大B细胞淋巴瘤（DLBCL）的疗效及安全性.方法：116例DLBCL患者接受利妥昔单抗联合化疗方案,中位治疗4.73个疗程.初治DLBCL患者112例,其中R-CHOP 87例,R-CHOP样29例;26例在化疗中进展.采用Cheson标准及WHO标准评估疗效及不良反应.结果：116例患者全部进行疗效评价,总体客观有效率为75％ （87/116）,CR ＋CRu为34例（29.31％）,PR为53例（45.69％）,SD为12例（10.34％）,PD为17例（14.66％）.其中1例患者在挽救方案获得缓解后,接受自体干细胞支持下的超大剂量化疗.主要不良反应为骨髓抑制,消化道反应,轻度肝损伤,首次输注反应2例.中位随访52.3（3.2～86.5）月,6例死于肿瘤进展,2例死于骨髓抑制后合并重度感染.中位生存期60.54月（3.2～86.5）,其中1、3、5年总生存率分别为81％、63％、52％,无病生存期1、3、5年总生存率分别为76％、52％、47％.在影响疗效相关因素分析中,IPI评分Ann、Arbor分期和LDH水平为影响患者化疗效果的相关因素（P＜0.05）.结论：利妥昔单抗联合治疗DLBCL的疗效确切,不良反应可以耐受,效果与文献报道一致.     

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia

Rituximab (MabThera, Rituxan) is an anti-CD20 monoclonal antibody that induces lysis and apoptosis of normal and malignant human B cells, and sensitises malignant B cells to the cytotoxic effect of chemotherapy. In phase III trials in patients with indolent or aggressive B-cell non-Hodgkin's lymphoma (NHL), intravenous rituximab in combination with chemotherapy was more effective as first- or second-line therapy than chemotherapy alone in providing tumour remission and patient survival. Likewise, in patients with chronic lymphocytic leukaemia (CLL), rituximab in combination with chemotherapy appeared more effective than chemotherapy alone as either first- or second-line treatment. In addition, rituximab maintenance therapy was shown to significantly prolong tumour remission and patient survival in patients with indolent B-cell NHL or CLL. The combination of rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was cost effective as first-line therapy for advanced-stage diffuse large B-cell NHL compared with CHOP alone. Rituximab, either alone or in combination with chemotherapy, was generally well tolerated in patients with NHL or CLL. Overall, rituximab in combination with chemotherapy, is a valuable option for first- and second-line therapy in patients with advanced-stage indolent or aggressive B-cell NHL, and possibly those with B-cell CLL, and is included in current treatment guidelines for these indications. The drug is also potentially useful as maintenance therapy in patients with indolent B-cell NHL or CLL.     

Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia

Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukaemia (CLL). While the optimal use of the drug in many clinical settings has yet to be clarified, two pivotal trials have established rituximab as a viable treatment option in patients with relapsed or refractory indolent NHL, and as a standard first-line treatment option when combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (the most common type of aggressive NHL). The former was a noncomparative trial in relapsed indolent NHL (follicular and small lymphocytic subtypes) with clinical responses achieved in about half of patients treated with rituximab 375 mg/m(2) intravenously once weekly for 4 weeks, which was similar to some of the most encouraging results reported with traditional chemotherapeutic agents. The latter was a randomised comparison of eight cycles of CHOP plus rituximab 375 mg/m(2) intravenously (one dose per cycle) versus CHOP alone in previously untreated elderly patients (60 to 80 years of age) with diffuse large B-cell lymphoma. In this pivotal trial, 2-year event-free and overall survival were significantly higher with rituximab plus CHOP, and there was no increase in clinically significant adverse effects compared with CHOP alone. Treatment with rituximab is generally well tolerated, particularly in terms of adverse haematological effects and serious or opportunistic infections relative to standard chemotherapy. Infusion-related reactions occur in the majority of patients treated with rituximab; these are usually mild to moderate flu-like symptoms that decrease in frequency with subsequent infusions. In approximately 10% of patients, however, severe infusion-related reactions develop (e.g. bronchospasm, hypotension). These reactions are usually reversible with appropriate interventions and supportive care but there have been rare reports of fatalities. CONCLUSIONS: Clinical trials with rituximab indicate that the drug has broad application to B-cell malignancies, although further clarification is needed to determine its optimal use in many of these clinical settings. Importantly, rituximab in combination with CHOP chemotherapy has emerged as a new treatment standard for previously untreated diffuse large B-cell lymphoma, at least in elderly patients. Compared with conventional chemotherapy, rituximab is associated with markedly reduced haematological events such as severe neutropenia, as well as associated infections. Rituximab may be particularly suitable for elderly patients or those with poor performance status, and its tolerability profile facilitates its use in combination with cytotoxic drugs. PHARMACODYNAMIC PROPERTIES: Rituximab is a mouse/human chimaeric IgG(1)-kappa monoclonal antibody that targets the CD20 antigen found on the surface of malignant and normal B lymphocytes. Although treatment with rituximab induces lymphopenia in most patients, typically lasting about 6 months, a full recovery of B lymphocytes in the peripheral blood is usually seen 9-12 months after therapy, as CD20 is not expressed on haematopoietic stem cells. CD20 is, however, expressed on >90% of B-cell non-Hodgkin's lymphomas (NHL) and to a lesser degree on B-cell chronic lymphocytic leukaemia (CLL) cells.Although not fully elucidated, the cytotoxic effects of rituximab on CD20-positive malignant B cells appears to involve complement-dependent cytotoxicity, complement-dependent cellular cytotoxicity, antibody-dependent cellular cytotoxicity and induction of apoptosis. In addition, in vitro data indicate that rituximab sensitises tumour cells to the effects of conventional chemotherapeutic drugs. PHARMACOKINETIC PROPERTIES: Serum rituximab concentrations increased in proportion to dose across a wide range of single- and multiple-dose intravenous regimens in patients with B-cell NHL. When administll NHL. When administered at a dose of 375 mg/m(2) once weekly for 4 weeks in a pivotal trial in patients with relapsed or refractory indolent B-cell NHL (follicular or small lymphocytic subtypes), peak serum concentrations essentially doubled from the first (239.1 mg/L) to the fourth (460.7 mg/L) infusion, while elimination half-life (t(1/2)) increased from 76.3 to 205.8 hours (3.2 to 8.6 days). The concomitant increase in serum rituximab concentrations and t(1/2) with each successive infusion may be due, at least in part, to the elimination of circulating CD20-positive B cells and reduction or saturation of CD20-binding sites after the initial infusions of rituximab. The pharmacokinetic properties of rituximab are also characterised by wide inter-individual variability, and serum drug concentrations that are correlated with clinical response. Although pharmacokinetic data are limited in patients with aggressive forms of NHL, such as diffuse large B-cell lymphoma, rituximab appears to have a similar pharmacokinetic profile in these patients to that in patients with indolent B-cell NHL. The pharmacokinetics of rituximab are also reported to be similar whether the drug is administered with or without cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. THERAPEUTIC USE: A number of studies have demonstrated efficacy of intravenous rituximab in patients with various lymphoid malignancies of B-cell origin, including indolent (e.g. follicular lymphoma) and aggressive (e.g. diffuse large B-cell lymphoma) forms of NHL, and CLL, but the drug has not yet been approved for use in CLL, and approved indications in NHL vary between countries. In the US, for example, rituximab is available for the treatment of patients with low-grade or follicular, relapsed or refractory, CD20-positive B-cell NHL. In Europe, the drug has similar approval for relapsed or refractory follicular NHL as in the US, but has also been approved for use in combination with CHOP chemotherapy for the most common aggressive form of NHL (CD20-positive, diffuse large B-cell lymphoma). Rituximab was approved for these indications primarily on the basis of results from two pivotal trials. In Japan, rituximab has been approved for indolent B-cell NHL and mantle cell lymphoma (an aggressive form of B-cell NHL), primarily on the basis of results of a Japanese phase II trial. Indolent NHL: Results of several studies evaluating rituximab 375 mg/m(2) once weekly for 4 weeks in patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic lymphomas) showed objective response (OR) rates ranging from approximately 40-60% in those receiving the drug for relapsed or refractory indolent B-cell NHL, and slightly higher (50-70%) for those receiving rituximab as first-line therapy. In a pivotal trial in 166 patients with relapsed or refractory low-grade or follicular B-cell NHL, intent-to-treat (ITT) analysis showed an OR rate of 48%, and a projected median time to progression of 13 months.Encouraging data are also emerging on the use of rituximab in combination with chemotherapeutic agents (e.g. CHOP, fludarabine-containing regimens) or other drugs (e.g. interferon-alpha2a) in previously untreated patients with indolent forms of B-cell NHL (primarily follicular and small lymphocytic subtypes). Rates for OR were consistently around 95%, with the majority being complete responses (CRs). Follow-up data from a study in 40 patients with low-grade or follicular B-cell NHL treated with rituximab plus CHOP as first-line therapy showed that responses were durable with a progression-free survival and median duration of response >5 years.Bcl-2 gene rearrangement (t14;18) occurs in malignant cells in up to 85% of patients with follicular lymphoma, and minimal residual disease in peripheral blood and bone marrow can be monitored using polymerase chain reaction (PCR). In several studies assessing blood and/or bone marrow, rituximab has achieved molecular response (conversion from PCR-positive to PCR-negative bcl-2 status) in at least half of the patients. Aggressive NHL: Studies with rituximab as monotherapy in aggressive B-cell NHL, a potentially curable disorder, have generally been restricted to patients with relapsed or recurrent disease, since CHOP has traditionally been the standard first-line treatment regimen. However, promising results from phase II monotherapy studies prompted further clinical investigation of rituximab in conjunction with chemotherapy. Thus, most studies with rituximab in patients with aggressive forms of B-cell NHL have involved combination therapy, including a pivotal randomised trial comparing eight cycles of standard CHOP therapy plus rituximab 375 mg/m(2) (one dose per cycle) versus CHOP alone in 399 previously untreated elderly patients (60-80 years of age) with diffuse large B-cell lymphoma. Results of the pivotal trial showed a clear advantage for rituximab plus CHOP versus CHOP in terms of event-free survival (primary endpoint) at 2 years (57% vs 38%, p < 0.001). Overall survival at 2 years (70% vs 57%, p < 0.01) and CR rate (76% vs 63%, p < 0.01) were also higher with the rituximab-CHOP combination. Other, smaller trials with rituximab in combination with CHOP or other chemotherapeutic regimens, either as first-line therapy or for patients with relapsed or refractory aggressive B-cell NHL, have also shown promising results in terms of clinical response rates.CLL: In relatively small trials (n < 40) conducted primarily in patients with relapsed or refractory B-cell CLL, rituximab monotherapy (various regimens) achieved OR rates of 23-45%, with median duration of response ranging from approximately 3-10 months. (ABSTRACT TRUNCATED)     

Complete remission of primary bilateral adrenal lymphoma achieved by Rituximab-CHOP chemotherapy

Primary adrenal lymphoma (PAL) is an exceedingly rare disease. Because of its rareness, uncertain etiology, variable duration of survival, unremarkable clinical presentations and unsatisfied therapeutic strategies, its treatment has always been unsatisfactory. Here we report a 50-year-old male patient with primary bilateral adrenal diffuse large B-cell lymphoma. He was treated with surgery followed by combined chemotherapy using R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). He achieved complete remission after 3 cycles of chemotherapy. At present, he is considered free of tumor at 3 years after chemotherapy. Our case report demonstrates that patients with primary bilateral adrenal diffuse large B-cell lymphoma may achieve a good outcome using R-CHOP chemotherapy. To the best of our knowledge, our patient who achieved complete remission after R-CHOP chemotherapy has had the longest survival as published in the literature.     

Cost effectiveness of combination therapy with pioglitazone for type 2 diabetes mellitus from a german statutory healthcare perspective

BACKGROUND: Pioglitazone has been approved in Europe for oral combination therapy for type 2 diabetes mellitus. Along with other agents of the thiazolidinedione class, it has a novel intracellular mechanism of action. Clinical trials with pioglitazone have confirmed a strong product profile in terms of control of blood glucose and lipids. However, the drug acquisition cost for pioglitazone is greater than standard medications for type 2 diabetes. Long-term data regarding the cost effectiveness of pioglitazone-based combination therapy are not available. OBJECTIVE: To evaluate, using a decision analysis model, the cost effectiveness of pioglitazone-based combination therapy compared with relevant alternative medications for the treatment of type 2 diabetes in Germany. METHODS: This study compared the clinical effects and costs of pioglitazone 30 mg added to metformin in patients who failed metformin monotherapy and pioglitazone added to a sulphonylurea in patients who failed sulphonylurea monotherapy, with the most relevant treatment alternatives. A published and validated Markov model was adapted to reflect the management of type 2 diabetes. This simulated the number of severe complications occurring and the mean life expectancy of a diabetic cohort, which was based on the overweight group of the UK Prospective Diabetes Study at year 6 of follow-up. Drug treatment costs, other costs for general management of type 2 diabetes and the costs of complications were combined to compute overall lifetime treatment costs from the perspective of the German statutory healthcare system in 2002. RESULTS: Combination therapy with pioglitazone/metformin was associated with a higher life expectancy (15.2 years) relative to sulphonylurea/metformin (14.9 years) or acarbose/metformin (14.7 years). Likewise, pioglitazone/sulphonylurea (15.5 years) was superior to metformin/sulphonylurea (14.9 years) and acarbose/sulphonylurea (14.8 years). Undiscounted incremental cost-effectiveness ratios in comparison to the next best strategy were euro20,002 per life-year gained (LYG) for pioglitazone/metformin versus sulphonylurea/metformin, and euro8707 per LYG for pioglitazone/sulphonylurea versus metformin/sulphonylurea. After discounting costs and life expectancy at 5% per year, the incremental cost-effectiveness ratio was euro47 636 per LYG for pioglitazone/metformin versus sulphonylurea/metformin, and euro19 745 per LYG for pioglitazone/sulphonylurea versus metformin/sulphonylurea. CONCLUSIONS: In this model, with its underlying assumptions and data, combination therapy with pioglitazone increased life expectancy in overweight type 2 diabetes patients at acceptable cost compared with other well established medications in Germany. These findings should be re-evaluated as soon as additional evidence becomes available from the currently ongoing long-term clinical and economic studies.     

利妥昔单抗联合CHOP化疗方案治疗CD20阳性B细胞性非霍奇金淋巴瘤疗效观察

目的观察利妥昔单抗(美罗华)联合CHOP化疗方案治疗CD20阳性B细胞性非霍奇金淋巴瘤的疗效及安全性。方法将23例B细胞非霍奇金淋巴瘤患者随机分为联合组12例和CHOP组11例。联合组采用美罗华联合CHOP方案治疗;CHOP组单用CHOP方案治疗。2组均每3周为1个循环周期,6个周期后观察2组的疗效及不良反应。结果联合组完全缓解率及总有效率略高于CHOP组,但差异均无统计学意义(P>0.05)。随访1年后,联合组无进展生存率及总体生存率略优于CHOP组,但差异均无统计学意义(P>0.05)。2组不良反应发生率比较差异无统计学意义(P>0.05)。2组所发生的各类不良反应总体严重程度比较差异无统计学意义(P>0.05)。结论美罗华联合CHOP化疗方案治疗CD20阳性B细胞性非霍奇金淋巴瘤的效果略优于CHOP方案,且与CHOP方案不良反应相当,安全性无差异。     

以吉西他滨为基础的化疗方案治疗初治弥漫大B细胞淋巴瘤的临床观察

目的观察比较R-GDP方案和R-CHOP方案治疗初治弥漫大B细胞淋巴瘤的疗效、生存和毒副反应。方法 100例DLBCL患者随机分为R-GDP组和R-CHOP组,4个周期后评价疗效,并随访统计比较总生存期及无疾病进展生存期。结果 (1)近期疗效:R-GDP组总体缓解率91.66%;R-CHOP组总体缓解率86.54%。两组比较差异无统计学意义(P=0.413)。(2)远期疗效:R-GDP组平均OS为32.730个月,R-CHOP组平均OS为31.623个月,两组OS比较差异无统计学意义(P=0.394)。R-GDP组平均PFS为25.137个月,R-CHOP组平均PFS为25.202个月,两组PFS比较差异无统计学意义(P=0.951)。(3)毒副反应:R-CHOP组在脱发、心脏毒性、静脉炎发生率明显多于R-GDP组,两组比较差异有统计学意义(P<0.05)。结论 R-GDP方案与R-CHOP方案治疗初治DLBCL近期疗效与远期疗效均无明显差异,两者均可作为初治DLBCL的首选方案。R-GDP组不良反应轻,耐受性好。     

R-CHOP方案治疗弥漫性大B细胞淋巴瘤疗效分析

目的:探讨弥漫性大B细胞淋巴瘤采用R-CHOP方案治疗的临床效果。方法:将某院收治的80例弥漫性大B细胞淋巴瘤患者按照随机数字表法分为研究组(R-CHOP方案)与对照组(CHOP方案);对比两组治疗效果及安全性。结果:治疗后研究组总有效率较对照组高,淋巴瘤国际预后指数优于对照组(P<0.05);两组不良反应结果对比无统计学意义(P>0.05)。结论:弥漫性大B细胞淋巴瘤采用R-CHOP方案治疗的效果更为理想。     

Model-based design of rituximab dosage optimization in follicular non-Hodgkin's lymphoma

AIMS

Rituximab has dramatically improved the survival of patients with non-Hodgkin''s lymphoma (NHL). However, studies have suggested that the dose regimen currently used (i.e. 375 mg m⁻²) could be optimized. The aims of this study were to quantify the benefits of the new dose regimen for rituximab in follicular NHL (FL) patients using a previously validated PK–PD model and to design clinical trials investigating optimization of rituximab dosage.

METHODS

A PK–PD model was used to predict progression-free survival (PFS) of FL patients treated by rituximab alone in asymptomatic FL, and those treated by rituximab combined with chemotherapy (R-CHOP) in relapsed/resistant FL. This model accounts for the influence of a polymorphism in FCGR3A, the gene encoding the FcγRIIIa receptor, on clinical efficacy. Several induction and maintenance dose regimens using rituximab alone or in combination with conventional chemotherapy (CHOP) were tested. The benefits of rituximab dose adjustment for F carriers were investigated. The numbers of subjects required for the design of two-armed clinical trials were calculated using model-predicted PFS at a power of 80%.

RESULTS

The model predicted a potential benefit of 1500 mg m⁻² maintenance doses of rituximab for both rituximab monotherapy and R-CHOP. The model shows that the PFS of FCGR3A-F carriers remains lower than that of homozygous FCGR3A-VV patients, even with markedly increased rituximab doses.

CONCLUSION

Our results suggest a benefit of increasing doses of rituximab in FL, both during induction and maintenance. These results need to be confirmed in controlled clinical trials.     

CHOP和R-CHOP方案治疗弥漫性大B细胞淋巴瘤的成本-效果分析

目的：评价CHOP和利妥昔单抗联合CHOP（即R-CHOP）两种化疗治疗初治弥漫性大B细胞淋巴瘤的经济学效果。方法：46例患者随机分为2组,CHOP组16例,接受每3周为1个疗程的环磷酰胺＋阿霉素＋长春新碱＋口服泼尼松的CHOP治疗方案;R-CHOP组30例,接受在每个疗程开始的第1天联合使用利妥西单抗的R-CHOP治疗方案,平均疗程均为4.5;评价2组的疗效及不良反应,并进行成本-效果分析。结果：CHOP和R-CHOP组总有效率分别为81.3%和90.0%,总成本分别为367.51和25825.96元;成本-效果比分别为4.52和286.96,两者间增量成本-效果比为2926.26;不良反应发生率两组比较相似（68.8%vs73.3%）,差异无显著性（P=0.742）。结论：R-CHOP方案治疗CD20阳性的弥漫大B细胞型NHL与单纯CHOP方案相比总有效率略高,但CHOP方案成本-效果优于R-CHOP方案。     

利妥昔单抗联合CHOP化疗方案对淋巴瘤患者免疫球蛋白的影响

目的探讨利妥昔单抗联合CHOP化疗对非霍奇金淋巴瘤(Non-Hodgkin lymphoma,NHL)患者免疫球蛋白的影响。方法将96例NHL患者按随机数字表法分为2组,对照组48例,实施CHOP方案化疗。观察组48例,在对照组治疗基础上,加用375 mg/m2利妥昔单抗治疗,3周为1个周期,持续治疗6个周期,治疗前、每个周期结束后,采用快速免疫消浊比浊法测定患者IgA、IgG、IgM等免疫球蛋白水平变化。结果观察组总缓解率为85.42%,高于对照组的64.58%(P<0.05);观察组发热、寒战等发生率为39.58%,高于对照组的10.42%(P<0.01);2个周期后观察组IgA、IgG、IgM开始低于对照组(P<0.05)。结论 R-CHOP方案治疗NHL疗效显著,但易导致免疫球蛋白下降。