Minichromosome maintenance protein 6 (MCM6) is one of six proteins of the MCM family which are involved in the initiation of DNA replication and thus represent a marker of proliferating cells. Since the level of cell proliferation is the most valuable predictor of survival in mantle cell lymphoma (MCL), we investigated lymph node biopsy specimens from 70 patients immunohistochemically with a monoclonal antibody against MCM6. The percentage of MCM6 expressing lymphoma cells ranged from 12.0 to 95.6%, with a mean of 61.0%, and was significantly higher than the percentage of Ki-67-positive cells (P<0.0001). Surprisingly, the ratio of MCM6-positive cells to Ki-67-positive cells was higher than in normal stimulated peripheral blood mononuclear cells, indicating a cell early G1-phase arrest in MCL. A high MCM6 expression level of more than 75% positive cells was associated with a significantly shorter overall survival time (16 months) compared to MCL with a low MCM6 expression level of less than 25% (no median reached, P<0.0001). Multivariate analysis revealed MCM6 to be an independent predictor of survival that is superior to the international prognostic factor and the Ki-67 index. Therefore, aside from gene expression profiling, immunohistochemical detection of MCM6 seems to be the most promising marker for predicting the outcome in MCL.

/pdf/minichromosome-maintenance-protein-6-a-proliferation-marker-3cuav7rl73.pdf

Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma

Low dose palliative radiotherapy in low grade non-Hodgkin's lymphoma

The therapeutic efficacy of intensive chemotherapy (CHOP) versus palliative low-dose therapy (chlorambucil/prednisone, ChP) was studied in a randomized trial including 258 previously untreated patients with asymptomatic low-grade non-Hodgkin lymphomas stage III and IV. The patients were stratified according to histological subgroup (the Kiel classification). 113 patients with chronic lymphocytic leukemia (CLL), including B-CLL and leukemic lymphoplasmacytoid immunocytoma (1C), were evaluated separately and presented here. The therapeutic goal was to achieve an asymptomatic state in the ChP group, while in patients allocated to CHOP the intention was to reach complete remission. Thus, in the CHOP group a higher response rate was noted than in the ChP group but no statistically significant difference in overall survival was seen. The results do not support the use of intensive chemotherapy as first line therapy in symptomatic CLL.

Chlorambucil/Prednisone versus CHOP in Symptomatic Chronic Lymphocytic Leukemias of B-Cell type. A Randomized Trial.

Summary 18 malignant lymphomas with initial manifestation in bone were selected from the Bone Tumor Registry of Westfalia at the Munster institute of Pathology where they had been documented between 1975 and 1985, and evaluated under clinical, radiological and histological aspects. Non-Hodgkin lymphomas were reclassified according to the Kiel nomenclature. Paraffin-embedded material was subjected to immunobistocbemical analysis in order to assess the features that could add to the correct characterization of these lymphomas, and to their differentiation from other round cell tumors of bone. Non-Hodgkin lymphomas (NHL) were more common in the collective than Hodgkin's lymphomas (HL). of 13 NHL, 2 were of low, 11 of high-grade malignancy. The former comprised one centrocytic and one centroblastic/centrocytic, the latter 7 centroblastic, 2 immunoblastic, and 2 lympboblastic lymphomas. Seven NHL patients with localized tumors survived up to 11 years (mean survival span: 6 yrs) after local therapy (radiation and/or resection). Another NHL patient, however, had multiple bone lesions, and died within a year. Analysis for leukocyte common antigen was positive in 9/12 NHL cases, reaction with Ki-B-3, a marker of B-lymphocytes, was positive in 7/12 cases. No lymphoma cells were found to react positively with lysozyme, alpha1-antitrypsin, or alpha1-anticbymotrypsin. It is concluded that localized lymphomas of bone respond well to appropriate local therapy; immunhistocbemical investigation may be useful to characterize the true cellular origin of these tumors, and may help to differentiate them from other round cell tumors of bone.

Malignant lymphomas with primary bone manifestation.

Aim of this multicenter-study was to evaluate rate and duration of remissions and to examine toxicity of cladribine in low-grade lymphomas as first-line therapy or in first relapse using intermittent 2-hour-infusion of cladribine. A total of 294 courses, median of 5 courses per patient, were administered to 66 evaluable patients (53 previously untreated, 13 relapsed) with 5 mg/m2 cladribine given as intermittent 2-hour-infusion over 5 consecutive days for a maximum of 6 cycles every four weeks. Entities: 26 follicle center, 20 lymphoplasmacytoid, 12 mantle cell, 6 T-cell, 2 marginal zone lymphomas. Fifty of 66 patients responded to cladribine corresponding to an overall response rate of 76% (95% confidence interval (95% CI): 64%-85%) with 38% CR (95% CI: 26%-51%) and a median time of remission duration of 23 months (range 645+). The overall survival rate at 48 months was 72%. For 49 previously untreated patients with B-cell lymphomas the overall response rate was 86% (95% CI: 73%-94%) with a high CR rate ...

Intermittent 2-hour-infusion of cladribine as first-line therapy or in first relapse of progressive advanced low-grade and mantle cell lymphomas.

The Kiel classification provides a new subdivision of non-Hodgkin lymphomas into distinct entities showing different clinical and prognostic properties. In comparison with earlier classifications this system defines additional types of lymphoma (e.g. CC lymphoma, LP immunocytoma) (for abbreviations see text) which are to be considered separate entities also from a clinical point of view. By data derived from a multicenter prospective observation study (1,127 patients recruited from 1975 to 1980, follow-up until 1985) a precise definition of the clinical features of each lymphoma entity (e.g. frequency, age and sex distribution, patterns of initial involvement and spread of disease) was possible. In addition, the effect of radio- and/or chemotherapeutic measures was evaluated. Strictly localized disease (stage I/IE according to the Ann Arbor classification) occurred in 1.5 to 8% of patients with NHL of low-grade malignancy (comprising 69.4% of cases studied) and in 8 to 17% of patients with high-grade malignant NHL (comprising 30.2% of cases studied). Loco-regional irradiation alone was able to induce complete remission in 86 to 89% (CB and IB lymphomas) and in 100% (LP immunocytoma, CB-CC and CC lymphomas), respectively, of stage I/IE patients. Only CC and IB lymphomas showed a relevant risk of relapse (40% and 50%, respectively). Total lymphoid irradiation as able to induce stable complete remissions in about 50% of patients with stage III of CB-CC lymphoma. Probabilities of survival of patients with initial stages III and IV treated by several types of chemotherapy reflect different prognostic features of individual lymphoma entities.(ABSTRACT TRUNCATED AT 250 WORDS)

Klinische und prognostische Relevanz der Kiel-Klassifikation der Non-Hodgkin-Lymphome

Ziel der Studie war die Verbesserung der Remissionsqualitat durch Anwendung einer intensivierten Induktionstherapie, welche sich bei der kindlichen ALL bewahrt hat (Westberliner Therapieprotokoll); in

Patientenrekrutierung und Ergebnisse einer Vorphasestudie zur Therapie der akuten lymphatischen Leukämie und der akuten undifferenzierten Leukämie des Erwachsenen

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Klinische und prognostische Relevanz der Kiel-Klassifikation der Non-Hodgkin-Lymphome

Patientenrekrutierung und Ergebnisse einer Vorphasestudie zur Therapie der akuten lymphatischen Leukämie und der akuten undifferenzierten Leukämie des Erwachsenen