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On the basis of the retrospective analysis of 405 patients, suggesting the clinical relevance of the Kiel classification of non-Hodgkin lymphomas (NHL), a prospective multicenter study was started on October 1st, 1975, by the Kiel Lymphoma Study Group in order to further clarify the clinical and prognostic features of the different lymphoma entities defined by this histopathologic scheme. Diagnostic protocol provides initial staging evaluation according to a modification of the Ann Arbor classification. Therapeutic approach is based on the hypothesis that, like Hodgkin's disease, NHL originate, at least in part, as localized lymphatic or extralymphatic tumors. Thus, extended field irradiation is performed in stages I and II (except for lymphoblastic lymphoma in children and young adults) whereas in the more advanced stages III and IV (except for stage III of centroblastic-centrocytic lymphoma) chemotherapy with additional radiotherapy is applied. Until June 1979, 815 patients entered the study (69.7% with NHL of low-grade malignancy). For the interim evaluation underlying the present and the other papers of this series data of 511 patients were available. Survival of patients with NHL of low-grade malignancy significantly exceeds that of patients with NHL of high-grade malignancy. NHL with good prognosis such as chronic lymphocytic leukaemia and centroblastic-centrocytic lymphoma can be differentiated from NHL with a poor course such as lymphoblastic and immunoblastic lymphomas. In addition, the existence of a third group with an intermediate prognosis comprising centrocytic and centroblastic lymphomas and, possibly, also LP immunocytoma is suggested. However, different initial slope of survival curves shows that this latter group of NHL is not homogeneous with regard to prognosis.

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)

Peripheral blood cells from patients with acute leukaemia were stimulated in RPMI-medium with Phytohaemagglutinin (PHA) and/or Pokeweed-Mitogen (PWM). Samples of the cultures were taken at 3, 5 and 7 day intervals for cytological characterization. From 119 cultures from 65 patients 76 cultures from 47 patients could be analysed. Cultures stimulated with PHA and/or PWM showed in 43,4% a higher stimulation rate in comparison with cultures from normal persons. These findings are discussed in relation to the increased agar-colony growth of leukaemic cells after in vitro PHA-stimulation and transformation of blast cells.

Clinical and prognostic relevance of the Kiel classification of non-Hodgkin lymphomas (NHL) was investigated in 1127 patients entering a prospective multicenter observation study. Survival of the 782 (69.4 per cent) patients with low-grade malignant NHL (lymphocytic lymphomas, predominantly B-CLL, LP immunocytoma, centrocytic lymphoma, centroblastic-centrocytic lymphoma) exceeded that of the 341 patients (30.2 per cent) with high-grade malignant NHL (centroblastic, immunoblastic, lymphoblastic lymphomas). Prognosis was best in centroblastic-centrocytic lymphoma and in B-CLL and least favorable in immunoblastic and lymphoblastic lymphomas. Survival of LP immunocytoma and centrocytic lymphoma patients was intermediate after 2 to 2.5 years of follow-up. Corresponding to histopathology, pattern of survival curves of low-grade malignant NHL (slow decline, no plateauing) differed from that of high-grade malignant NHL (rapid decline, subsequent plateauing). Prognosis of B-CLL was superior to that of LP immunocytoma. Stages I and II were more frequent in centroblastic-centrocytic lymphoma (21 per cent) than in LP immunocytoma (2.5 per cent) and centrocytic lymphoma (11 per cent). Ability of radiotherapy to induce stable complete remissions in stage III of centroblastic-centrocytic lymphoma indicates prolonged restriction of lymphoma to the lymphatic system. In immunoblastic and centroblastic lymphomas, stages I and II were diagnosed in 34 and 38 per cent of cases, respectively, but only in stage I/IE of centroblastic lymphoma prolonged remissions were achieved by radiotherapy. In advanced high-grade malignant NHL marked improvement of prognosis was solely possible by induction of complete remissions whereas in corresponding low-grade malignant lymphomas also partial remissions were prognostically relevant.

Clinical data of 48 patients with centrocytic, 83 patients with centroblastic/centrocytic and 64 patients with centroblastic lymphoma who had entered a prospective multicenter study of the Kiel Lymphoma Study Group since October 1975 were compared. Advanced (stage IV) disease at time of diagnosis, predominantly due to bone marrow infiltration, was most frequent in centrocytic (69% of patients) and in centroblastic/centrocytic (51% of patients) lymphomas as compared to only 28% of patients with centroblastic lymphoma. High survival probability of patients with localized centrocytic and centroblastic/centrocytic lymphomas after radiotherapy, contrasting with a worse prognosis of corresponding patients with centroblastic lymphoma, is compatible with the classification of these lymphoma entities as neoplasias of low-grade malignancy. However, as shown by this prospective and previous retrospective trials overall survival probability of patients with advanced centrocytic lymphoma was inferior to that observed in corresponding patients with centroblastic/centrocytic lymphoma. These findings suggest the possibility that patients with advanced centrocytic lymphoma occupy an intermediate position between typical low-grade and typical high-grade malignant non-Hodgkin lymphomas.

From 1976 until 1978, 136 adult patients with acute leukemia were treated in four hospitals in Berlin. A complete remission was achieved in 47 patients (35%). Twenty-six patients with non-lymphocytic acute leukemia, who had achieved a complete remission with induction chemotherapy consisting of daunorubicin (45 mg/m2/day, day 1, 2 and 3) and cytosine-arabinoside (100 mg/m2/day, continuous infusion, day 1 to day 7) were entered into a randomized trial. Thirteen patients were treated with an intermittent combination chemotherapy at 4-week intervals; the other group of patients received in addition a specific immunotherapy consisting of neuraminidase-modified allogeneic blast cells. The results revealed that the addition of this kind of immunotherapy did not increase the duration of first remission or survival.