Combination chemotherapy of diffuse large-cell non-Hodgkin's lymphoma--superiority of the adriamycin combination

In patients with diffuse large-cell non-Hodgkin's lymphoma, the results of combination chemotherapy containing adriamycin (ADM) were compared with those of combination chemotherapy without ADM. None of the patients had had any prior therapy and there was no difference in any other background factors for these two treatment groups. Of 32 patients treated without ADM, 19 (59%) achieved complete response (CR) and 12 (38%) achieved partial response (PR). Of 20 patients treated with ADM. 14 (70%) achieved CR and 6 (30%) achieved PR. For patients treated without ADM, median duration of CR was 9 months, projected 5-year relapse-free rate was 27%, median survival time was 1 year 6 months and projected 5-year survival rate was 27%. For patients treated with ADM, median duration of CR was not reached, projected 5-year relapse-free rate was 85%, median survival time was 2 years 2 months and projected 5-year survival rate was 49%. Combination of ADM was superior and therefore should be used for the initial treatment of this type of non-Hodgkin's lymphoma.     

Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia

Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials.     

Final Results of Cooperative Study of VEPA [Vincristine, Cyclophosphamide (Endoxan), Prednisolone and Adriamycin] Therapy in Advanced Adult Non-Hodgkin's Lymphoma: Relation Between T- or B-Cell Phenotype and Response

One hundred previously untreated adult patients with advancednon-Hodgkin's lymphomas were treated with VEPA (vincristine,cyclophosphamide, prednisolone and adriamycin in combination)therapy. The overall complete remission rate was 52%. The completeremission rate was markedly higher in the patients with lineage-undeterminedlymphomas (72.2%) as well as in the patients with B(non-T)-celllymphomas (58.5%) than in the patients with T-cell lymphomas(36.6%). The median duration of complete remission has not beenreached for lineage-undetermined lymphomas and most (77%) ofthe patients have been in remission for more than 2-yr, whilethe median duration of complete remission for B(non-T)-celltype was 16 mo with a 3-yr remission rate of 14%, and medianduration for the T-cell type was only 4 mo with a 2-yr remissionrate of 15% or less. Both complete remission and cell lineageof lymphomas markedly affected the survival period. Of the patientswho were not induced into complete remission, about 90% diedwithin 12 mo regardless of the cell lineage of the lymphoma,and their median survival was only 5–7 mo. On the otherhand, more than 90% of the patients with lineage-undeterminedlymphomas who were induced into complete remission are stillalive after 36 mo. Median survival was 37 mo and the 3-yr survivalrate was 56.1% in the case of B(non-T)-cell lymphoma with completeremission. Even in the T-cell lymphomas, significantly (a fewmonths) longer survival time will be expected in the patientsin complete remission. These facts indicate that complete remissioninduced by VEPA therapy contributes greatly to longer survivalof the patients, but its contribution is limited by the celllineage of the lymphoma. B(non-T)-cell lymphoma as well as lineage-undeterminedlymphoma responded well to VEPA therapy and some of the patientsmay be cured. On the other hand, T-cell lymphoma responded poorlyto VEPA therapy.     

Long-term follow-up results of adult patients with acute lymphocytic leukemia or lymphoblastic lymphoma treated with short-term, alternating non-cross-resistant chemotherapy: Japan Clinical Oncology Group Study 8702. Lymphoma Study Group.

BACKGROUND: Patients with acute lymphocytic leukemia (ALL) and those with lymphoblastic lymphoma (LBL) have overlapping clinical and immunophenotypic features and they have been treated with the same or very similar chemotherapy regimens. The goal of this multi-institutional phase II trial was to evaluate the therapeutic efficacy of a short-term, six-drug chemotherapy regimen for adult patients with untreated ALL or LBL. METHODS: Forty-six eligible patients, 41 with ALL and five with LBL, were treated with a short-term (planned total therapy duration; 36-38 weeks), simplified chemotherapy program; two courses of VEPA-L (vincristine, cyclophosphamide, prednisolone, doxorubicin, I-asparaginase plus intrathecal methotrexate and prednisolone) followed by four courses of M-VEPA (methotrexate plus VEPA), without the traditional maintenance therapy using daily 6-mercaptopurine and weekly methotrexate. RESULTS: Thirty-six (78%; 95% confidence interval 64-89%) of the 46 eligible patients achieved complete remission (CR). Among the 36 patients who achieved CR, four (11%) died of treatment complications, 26 (72%) relapsed and six (17%) remain alive in continuous CR. The median survival for all 46 eligible patients is 14 months and the median disease-free survival (DFS) for the 36 patients who achieved CR is 11 months. The estimate of the proportion of survival at 7 years of all 46 eligible patients is 15% at a median follow-up time of 96 months and that of DFS of the 36 patients achieving CR is 17% at a median follow-up time of 93 months. Subgroup analysis showed that an elevated serum C-reactive protein (CRP) level, age of 30 years or older, the presence of B-symptom and T-cell phenotype were likely to be associated with shortened survival. Although the observed CR rate (78%) is within the range of satisfaction, the long-term survival rate (15%) is inferior to those of published programs incorporating maintenance therapy. CONCLUSIONS: A fraction of adult patients with ALL or LBL are curable with a short-term, six-drug chemotherapy regimen. However, this simplified therapy of shorter duration cannot be recommended.     

Comparison of CHOP versus VEPA Therapy in Patients with Lymphoma Type of Adult T-cell Leukemia

Forty-six Japanese patients with lymphoma type of adult T-cell leukemia (ATL) were treated with one of the 4-drug combinations, CHOP or VEPA regimen. Fourteen patients were treated with CHOP, while 32 were treated with VEPA. The complete response i(CR) rate and the 5-year survival rate of patients treated with CHOP were 35.7% and 7.1%, respectively, while for those treated with VEPA the rates were 43.8% and 18.7%, respectively. Only two patients treated with CHOP survived for more than 1 year, while the others died within 1 year. On the other hand, 13 patients treated with VEPA survived for more than 1 year. The 32 VEF'A-treated patients were divided into two groups according to the duration of survival: (A) 13 surviving for more than 1 year, and (B) 19 surviving for less than 1 year. They were compared for pretreatment characteristics. The differences between the two groups related to hepatomegaly, the presence of B symptoms, lactic dehydrogenase (LDH) and calcium levels. The results indicate that these factors are important in predicting the response and survival of patients with lymphoma type of ATL.     

Clinical Observation of FMD Regimen:Fludarabine,Mitoxantrone, Dexamethasone, in Treatment of Non-Hodgkin''s Lymphoma

Objective  To evaluate the clinical effectivity and toxicity of the regimen FMD (fludarabine, mitoxantrone, dexamethasone) in patients with non-Hodgkin’s lymphoma. Methods  Thirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell lymphoma, received FMD. Treatment comprised: fludarabine 25∼30 mg/m² days 1∼3, mitoxantrone 8∼10 mg/m² day 1, and dexamethasone 20∼30 mg/m² days 1∼5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole, fluconazole, acyclovir and immunoglobulin. Results  Of the thirty-two patients treated, the complete response (CR) rate, partial response (PR) rate and overall response (OR) rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7% and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3∼4 neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3∼4 thrombocytopenia. At a median follow-up of 24 (5∼54) months, the 2-year overall-survival rate and progression-free survival rate were (87.5 ± 1.4)% and (83.3 ± 1.6)% respectively. The 2-year OS and PFS rates of the indolent group were (93.75 ± 6.25)% and (87.5 ± 8.54)%. Conclusion  FMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin’s lymphoma, especially in indolent B-cell lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.     

Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M

One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients.     

High-dose chemotherapy with autologous hematopoietic stem cell transplantation for non-Hodgkin's lymphoma in complete response as consolidation therapy, second report

High-dose chemotherapy followed by autologous peripheral blood transplantation (HD-APBSCT) is a therapeutic option for patients with non-Hodgkin's lymphoma (NHL) after complete remission (CR) as consolidation therapy. In this report we describe a retrospective study of such treatment. A total of 38 patients with NHL were treated between November 19 9 1 and March 2005. At five years,the rate of disease-free survival (DFS) and overall survival (OS) was 64.3% and 66.5%, respectively. Patients who underwent transplantation in first CR had a 5-year probability of disease-free survival of 71.6% compared with 35.7% for those who were in second CR at the time of transplantation (p=0.10). In a monovariate analysis, second CR status at the time of transplantation was a relatively adverse predictor of DFS. None of those factors containing surface markers were significantly associated with clinical variables such as the CR status at the time of transplantation. Thirty high intermediate risk and high risk patients with aggressive B-cell lymphoma had a better outcome than patients treated with standard chemotherapy. In this study, 8 patients with T-cell lymphoma had a 3-year DFS and OS of 87.5% and 87.5%, respectively. HDT-APBSCT is a candidate for consolidation therapy for high-intermediate risk and high risk patients with aggressive B-cell and T-cell lymphoma.     

High-dose therapy and autologous stem cell transplantation in Korean patients with aggressive T/NK-cell lymphoma

The proportion of aggressive T/NK-cell lymphoma in Korea is larger than in the West, and it shows a lower response to conventional chemotherapy and poorer survival than diffuse large B-cell lymphoma. This study was undertaken to evaluate the response rate and survival and to document the prognostic factors in patients with T/NK-cell lymphoma who have undergone high-dose therapy (HDT). Eligibility for the study was a mature T/NK-cell lymphoma with initially poor risk (as high or high intermediate risk on age-adjusted International Prognostic Index) or relapsed cases. Twenty-eight patients from 6 centers were reviewed retrospectively. The M : F ratio was 20:8, and median age was 36 years (range 16--60 years). Twelve patients had unspecified peripheral T-cell lymphomas, 7 anaplastic large-cell lymphomas, 6 nasal T/NK-cell lymphomas, and 3 angioimmunoblastic T-cell lymphomas. Disease status at transplant were initially poor risk in 15, chemosensitive relapse in 8 and chemo-resistant relapse in 5 patients, respectively. A complete response (CR) after HDT comprised 20 patients, including 16 with continued CR. Absolute neutrophil count ( > 500/microl) recovered at a median 11 days after autologous stem cell transplantation in 26 patients. Two therapy-related mortalities occurred. Estimated 3-year event-free survival and overall survival (OS) (+/- SE) were 24+/- 9 and 42+/- 10 months, respectively. Only CR status after HDT influenced OS (P=0.000). Therefore, an initial approach with effective induction and HDT may result in a better outcome in T/NK-cell lymphoma.     

Major Prognostic Factors of Adult Patients with Advanced B-Cell Lymphoma Treated with Vincristine, Cyclophosphamide, Prednisone and Doxorubicin (VEPA) or VEPA plus Methotrexate (VEPA-M)

Eighty-two adult patients with advanced B-lymphoma, treatedbetween 1981 and 1983 with VEPA (vincristine, cyclophosphamide,prednisolone and doxorubicin) or VEPA-M (VEPA plus methotrexate)in a prospective randomized fashion, were evaluated for pretreatmentcharacteristics. The overall complete response (CR) and the4-year survival rates were 74% and 45%, respectively. The relapserate was 51%. Stage of disease only was negatively associatedwith the CR rate in a multivariate analysis. The primary extranodaltumor site other than upper gastrointestinal (GI) tract andhigh grade pathology were found to affect disease-free survivaladversely in a Cox proportional hazards model. Poor performancestatus, advanced stage, primary extranodal tumor site otherthan upper GI tract, advanced age, high grade pathology andprior therapy by either surgery or radiation, were significantlyassociated with shortened survival in a Cox proportional hazardsmodel. These results indicate advanced B-lymphoma in Japan tobe generally similar to advanced non-Hodgkin's lymphoma in theWest in terms of prognostic factor characteristics, but theimportance of the primary site in predicting survival has notbeen reported in the West. Also, the lack of a survival plateauin patients with diffuse large cell lymphoma indicates moreintensive chemotherapy regimens than VEPA or VEPA-M to be needed.It was also found that the significant prognostic factors inpatients with advanced B-lymphoma were very different from thosewith T-lymphoma. The five factors: pathology, stage, primarysite, age, prior therapy by surgery or radiation, for whichthe risk ratio was more than 2.3, were used to construct a modelcontaining 23 categories of patients running an increasing riskof shortened survival; this divided patients into three groups.The CR and 4-year survival rates of low-, moderate- and high-riskgroups were 90% and 74%, 74% and 58%, and 50% and 5%, respectively.The risk-grouping provides indications for determining optimaltherapy for individual patients and the need for new therapeutictrials in patients at high risk.     

Rituximab in combination with platinum-containing chemotherapy in patients with relapsed or primary refractory diffuse large B-cell lymphoma

The aim of the study was to evaluate the efficacy of a regimen consisting of rituximab and a platinum-containing chemotherapy with either Ifosfamide, Carboplatin and Etoposide (ICE) or Cisplatin, high-dose Ara-C and Dexamethasone (DHAP) in patients with relapsed or primary refractory diffuse large B-cell lymphoma. Ten patients with relapsed or primary refractory diffuse large B-cell lymphoma were treated from June 2000 until May 2001 with a platinum-containing chemotherapy regimen according to the ICE- or DHAP-protocol in combination with rituximab at the University of Muenster. Two cycles of ICE or DHAP and rituximab were given. In case of at least a minor response after 2 cycles, 2 additional cycles of the same combination were applied. Response rate, remission duration and duration of survival were evaluated. All 10 patients could be analysed with respect to these endpoints. No treatment related mortality was observed. The response rate (CR/PR) was 60% (10/50%). Twenty percent of the patients had progressive disease. The median duration of remission and survival was 3 and 3.5 months, respectively (range: 1-6 and 1-7 months, respectively), the survival rate was 10%. Eight of 10 patients died because of their underlying disease with short remission duration, 1 patient died of complications of allogeneic transplantation in CR. In conclusion, the combination of platinum-containing chemotherapy (ICE or DHAP) with rituximab demonstrates significant activity in intensively pretreated patients with relapsed or primary refractory diffuse large B-cell lymphoma. Considering the short duration of remission and survival, respectively, other experimental therapeutic approaches (e.g. allogeneic stem cell transplantation, radioimmunotherapy) should be pursued following this treatment in order to induce long-term remission.     

Follow-up results of a phase II study of ibritumomab tiuxetan radioimmunotherapy in patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma and mild thrombocytopenia

This report presents updated time-to-event variables from a multicenter phase II trial of reduced-dose 90Y ibritumomab tiuxetan in patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL) and mild thrombocytopenia (platelet counts of 100 to 149 x 10(9) platelets/L). Patients received a single course of ibritumomab tiuxetan radioimmunotherapy, with 90Y ibritumomab tiuxetan administered at 0.3 mCi/kg (compared to a standard dose of 0.4 mCi/kg). In 30 patients, the overall response rate was 83%, with complete responses (confirmed [CR] and unconfirmed [CRu]) of 47%. Median follow-up time is currently 36.5 months (range: 7.5-54.9+ months). Median duration of response was 11.5 months (range: 1.0-53.9 months), median time to progression was 9.4 months (range: 1.7-54.8+ months), and median time to next lymphoma therapy was 14.6 months (range: 2.3-54.9 months). Median overall survival time has not yet been reached. Long-term responses, defined as time to progression of 12 months or greater, have been seen in 14 of 30 patients (47%) overall, and 12 of 14 CR/CRu patients (86%). Toxicities were primarily hematologic and reversible. No additional long-term adverse events have been observed in the follow-up period, and treatment did not preclude subsequent lymphoma therapies.     

原发性乳腺淋巴瘤27例临床分析并文献复习

背景与目的:原发性乳腺淋巴瘤(primary breast lymphoma,PBL)发病率低,预后较差.本研究旨在分析该病例的临床和病理特征,从而探讨PBL的合理治疗模式.方法:收集并回顾性分析1976年到2005年间在中山大学肿瘤防治中心诊断为PBL,并接受治疗的27例患者的临床资料和治疗情况.结果:27例中有26例女性和1例男性患者;年龄12～84岁;90%的患者为Ⅰ E期或ⅡE期.按照WHO 2001淋巴瘤病理分类系统,有22例B细胞性淋巴瘤(17例弥漫大B细胞性淋巴瘤,2例黏膜相关性淋巴瘤,1例边缘区淋巴瘤,2例未能分类),3例外周T细胞性淋巴瘤,2例患者的病理类型未能分类.初始治疗时有20例患者接受了综合治疗,其中8例患者为根治术加术后化疗,12例患者为肿物切除术后加全身化疗,两组的5年生存率分别为23.0%和58.0%(P=0.006);其余有5例患者仅接受全身化疗,2例患者仅接受肿物切除手术.24例患者在初始治疗后取得完全缓解,1例患者部分缓解,2例患者疾病进展.随访时间1个月～10年,中位随访时间38个月.全组患者的5年总生存率和无病生存率分别是47.0%和23.0%;其中20例中高度恶性淋巴瘤患者(17例弥漫大B细胞性淋巴瘤和3例外周T细胞性淋巴瘤)的5年总生存率和无病生存率分别是48.0%和27.0%;随访中有16例复发,部位见于同侧乳腺6例、对侧乳腺4例、中枢神经系统(central nervous system,CNS)3例、骨髓1例和淋巴结侵犯2例.结论:PBL的病理类型以中高度恶性淋巴瘤为主;根治性手术在其治疗中作用有限,肿物切除术加术后化疗和放疗的效果较好.PBL患者易发生CNS复发,在随访中应定期进行颅脑CT或MR检查.     

Lennert's lymphoma. A clinicopathologic study with emphasis on phenotype and its relationship to survival

In this report we describe the results of a clinical and immunohistochemical analysis of 11 consecutive patients with the specific clinicopathologic entity of Lennert's lymphoma (non-Hodgkin's malignant lymphoma with a multifocal epithelioid histiocytic reaction [MLEH]) evaluated at the Arizona Cancer Center. Detailed immunophenotyping of ten patients showed that seven patients (73%) had an activated "novel" T-cell phenotype, indicative of peripheral T cell lymphoma (PTL). Additionally, six of these seven PTL patients had T-helper (Leu-3) antigen expression to the exclusion of T-suppressor (Leu-2) expression. Three patients, in complete contrast, had a B-cell lymphoma with monoclonal immunoglobulin expression. The B-cell MLEH were morphologically indistinguishable from T-cell MLEH. Clinically, the initial diagnosis proved difficult; ten of the 11 patients were initially misdiagnosed, most often as another lymphoid disorder or as granulomatous disease (mean delay of 10 months in diagnosis from onset of symptoms). The median survival of all patients was 20 months (1 to 45+ months) with two apparent subgroups: those who had rapid progression of disease with a median survival of 5 months, all of T-cell phenotype; and a small group whose median survival has not yet been reached, all of B-cell phenotype. Our results suggest that the immunophenotype, B-cell versus T-cell, may be a major predictor of survival, with B-cell MLEH patients having a longer survival than those of T-cell type.     

Treatment outcome and pattern of failure in 77 patients with sinonasal natural killer/T-cell or T-cell lymphoma

BACKGROUND: Sinonasal natural killer (NK)/T-cell or T-cell lymphoma behaves quite differently from other lymphomas. The objective of this study was to investigate clinical features, treatment outcomes, and failure patterns in patients with this type of sinonasal lymphoma. METHODS: From September, 1977 to December, 2000, 77 patients with sinonasal NK/T-cell lymphoma or T-cell lymphoma who had received radiotherapy (R/T), chemotherapy (C/T), or both (R/T and C/T) were evaluated retrospectively. RESULTS: Fifty-six patients (73%) had locoregional disease only, and 21 patients (27%) had systemic involvement. Forty-four patients (57%) achieved a complete remission (CR). The 5-year overall survival rate was 36% (median follow-up, 89 months). Achievement of CR was the only prognostic factor for survival in multivariate analysis. Among patients with locoregional disease, the CR rate was 63%, and the 5-year overall survival rate was 42%. Combined R/T and C/T or R/T alone resulted in better survival compared with C/T alone (5-year survival rates, 59%, 50%, and 15%, respectively; P = 0.01). Incidences of locoregional and systemic failure were 43% and 30%, respectively. Outcome was dismal for patients with systemic disease, with a CR rate of 43% and a 5-year survival rate of 25%. Only 2 of 21 patients had sustained remissions. The locoregional and systemic failure rates were 57% and 71%, respectively. CONCLUSIONS: Treatment outcomes were unsatisfactory for patients with locoregional and systemic sinonasal NK/T-cell or T-cell lymphoma. R/T could not control locoregional disease satisfactorily, and C/T was unable to eradicate systemic disease in many patients. High-dose therapy may be worth studying in these patients. New treatments should be investigated to increase remission rates, prevent failure, and improve survival.     

Non-Hodgkin's lymphoma: correlation of cell surface marker phenotype with clinical features and prognosis

The correlation of surface marker phenotype with prognosis was analysed in 64 patients with non-Hodgkin's lymphoma who had been treated in Shikoku Cancer Center Hospital. B-cell lymphomas (21 cases) had significantly better prognosis than T-cell lymphomas (21 cases). The complete remission (CR) rate was 52%, and the 50% survival time was 13 months for T-cell lymphomas. All T-cell lymphoma patients died within 31 months. In B-cell lymphomas, on the other hand, the CR rate was 100%, 50% survival time was 30 months, and there were no cases of relapse in patients who had been in continuous CR for more than 2 years. About 40% of B-cell lymphomas appeared to have the potential for cure.     

Treatment of NonHodgkin’s lymphomas with rituximab in Slovene patients

The introduction of rituximab into the treatment of patients with NonHodgkin’s lymphomas has changed the long-term prognosis of patients with CD20 positive B cell lymphomas, especially follicular and diffuse large B-cell lymphomas (DLBCLs). The addition of rituximab to chemotherapy improves the overall response rate, prolongs the response duration and the overall survival both in patients with follicular and other indolent CD20 positive lymphomas, and DLBCLs. Maintenance treatment with rituximab in patients with indolent lymphomas further prolongs the remission duration, and some of the studies have also shown survival benefit. However, the maintenance therapy in aggressive lymphomas most probably gives no further improvement in patients, who have received rituximab already in the induction treatment. Rituximab has been used at the Institute of Oncology Ljubljana since 1998. In the period from 2004 to 2006, we have treated 340 patients with rituximab either as a single agent or in combination with chemotherapy. Our treatment group included 46.8% of patients with DLBCLs and 19.4% with follicular lymphomas. In majority of the patients, rituximab was given as the first-line treatment (54.4%), while 26.2% of patients received it as the second-line treatment and 19.4% of patients as the third or subsequent line of treatment. Among patients with indolent lymphomas, just 15% received rituximab as the first-line treatment. On the other hand, 75.9% of patients with aggressive lymphomas were treated with rituximab for newly diagnosed disease. About 67.4% of patients were treated with R–CHOP combination, while the others received different rituximab–chemotherapy combinations. The overall response rate regardless of the histological type of lymphoma was 78.8%, and the highest response rate was achieved in patients with aggressive follicular lymphomas (91.7%). The highest overall response rate was observed when rituximab was given as the first-line treatment in all lymphoma types except the mantle cell lymphoma (66.6% overall response rate for the first-line treatment versus 73.7% overall response rate for the second-line treatment). In 75% of patients regardless of the histological type of lymphoma, the response lasted more than 12 months; the median response duration has not been reached yet. In patients receiving rituximab as the first-line treatment, the median response duration also has not been reached yet, while for the second-line treatment, it was 25 months and for the third or subsequent line, 24 months. The longest disease-free survival was observed in patients with DLBCLs. The overall survival rate of all patients regardless of the type of lymphoma was 75% 26 months after the beginning of the treatment, and the median overall survival has not been reached yet. When analyzed by the lines of treatment—the median overall survival has not been reached in any line. The longest overall survival was observed in patients with indolent follicular lymphomas. The treatment results with rituximab at the Institute of Oncology Ljubljana are comparable to the results of larger randomized trials. According to the beneficial influence of rituximab on the long-term prognosis of patients with CD20 positive lymphomas, it became the standard of treatment in these patients.     

Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy.

BACKGROUND: High-dose therapy (HDT) with stem-cell support is the reference treatment for relapsed lymphoma, but is not appropriate for all patients. Conventional salvage chemotherapies have been used with limited efficacy and significant toxicity. Rituximab, gemcitabine and oxaliplatin are active as single agents in relapsed or refractory lymphoma, and have demonstrated synergistic effects in vitro and in vivo. PATIENTS AND METHODS: Forty-six patients with relapsed or refractory B-cell lymphoma received up to eight cycles of R-GemOx (rituximab 375 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) and oxaliplatin 100 mg/m(2) on day 2). The majority (72%) had diffuse large B-cell lymphoma. RESULTS: After four cycles of R-GemOx, the overall response rate was 83% [50% complete response (CR)/unconfirmed CR (CRu)]. High CR/CRu rates were observed in all histological subtypes. In patients who had previously received rituximab, the CR/CRu rate after eight cycles was 65%. The 2-year event-free and overall survival rates (median follow-up of 28 months) were 43% and 66%, respectively. Among responders, the probability of being disease free for 2 years was 62%. Treatment was generally well tolerated. CONCLUSION: R-GemOx shows promising activity with acceptable toxicity in patients with relapsed/refractory B-cell lymphoma who are not eligible for HDT.     

Update of the M. D. Anderson Cancer Center experience with hyper-CVAD and rituximab for the treatment of mantle cell and Burkitt-type lymphomas

Mantle cell lymphoma (MCL) and Burkitt lymphoma respond to initial intense therapies, such as hyper-CVAD (hyperfractionated cyclophosphamide/vincristine/doxorubicin/dexamethasone) alternating with high-dose methotrexate/cytarabine, to which the monoclonal antibody rituximab has recently been added. This report provides an update detailing the long-term outcome when this chemoimmunotherapy regimen is used as first-line therapy for newly diagnosed MCL, de novo Burkitt lymphoma, atypical Burkitt lymphoma, and mature B-cell acute lymphoblastic lymphoma (B-ALL). Ninety-seven patients with de novo MCL and 31 patients with Burkitt lymphoma, atypical Burkitt lymphoma, and B-ALL were treated with rituximab plus hyper-CVAD alternating with rituximab/methotrexate/cytarabine under different institutional trials approved by the University of Texas M. D. Anderson Cancer Center Institutional Review Board. Overall response rate (RR) for patients with MCL was 97% (complete response [CR]/unconfirmed CR rate, 87%). At a median follow-up of 4.8 months, the 5-year failure-free survival and OS rates were 48% and 65%, respectively. Among patients aged < or = 65 years, the 5 year failure-free survival was 60%. Patients with blastoid morphology have a 7-year survival rate of 47%. Toxicity was mainly hematologic but significant. Overall RR for patients with Burkitt lymphoma/atypical Burkitt lymphoma/B-ALL was 97% (CR rate, 86%). With a median follow-up of 22 months, the estimated 3-year OS, disease-free survival, and event-free survival rates were 89%, 88%, and 80%, respectively. Rituximab plus hyper-CVAD alternating with rituximab/methotrexate/cytarabine is an effective dose-intense chemoimmunotherapy program for untreated MCL, Burkitt lymphoma, atypical Burkitt lymphoma, and B-ALL. Toxicity is mainly hematologic and significant, but expected.     

Primary non-Hodgkin's lymphoma of the breast: retrospective analysis of prognosis and patterns of failure in two Australian centers

The breast is an uncommon site of presentation for primary non-Hodgkin's lymphoma, with prognosis and patterns of relapse still not clearly defined. A retrospective analysis of 21 patients presenting to 2 Australian centers during a 20-year period is presented. All patients were women and had a median age of 62 years. Fifteen patients (71%) had localized disease (12 unilateral and 3 bilateral), and 6 (29%) had regional lymph-node involvement. Histology was predominantly intermediate grade, with diffuse large B-cell lymphoma (DLBL) in 16 cases (76%). The most common treatment program was partial mastectomy followed by chemotherapy and radiation therapy (n = 12). Complete response (CR) to treatment was exhibited in 19 patients (90%), 11 of whom subsequently experienced relapse. Including the 2 patients who failed to exhibit an initial CR, the median time to disease progression was 23.4 months (range, 0-143 months), with a 5-year disease-free survival rate of 38% (+/- 12%). The actuarial median survival of all patients was 3.8 years, with bilateral breast involvement at presentation the only significant prognostic factor. The contralateral breast was the site of initial relapse in 3 patients (17%), all of whom subsequently died of disease. The actuarial rate of central nervous system (CNS) recurrence at 8 years was 39% (+/- 14%), occurring only in patients with diffuse large-cell histology. Our analysis suggests that DLBL presenting in the breast has a poor prognosis and characteristic patterns of failure. Targeted strategies such as CNS prophylaxis and contralateral breast irradiation might therefore improve prognosis and should be prospectively studied.