The Kiel classification of non-Hodgkin lymphomas (NHL) has established chronic lymphocytic leukemia (B-CLL) and immunocytoma (LP-IC) as separate entities of low-grade malignant NHL by morphological and immunohistochemical criteria. The clinical and prognostic relevance of this discrimination was evaluated in a prospective multicenter observation study by the Kiel Lymphoma Study Group. From 1975 to 1980, 430 previously untreated patients with B-CLL (n = 217) and LP-IC (n = 213)a were recruited and followed for up to 14 years. While the age and sex distribution and the incidence of clinical stages were quite similar in both entities major differences between initial manifestations in B-CLL and LP-IC became evident, e.g. in the incidence of bone marrow infiltration (99.5 vs. 86%), peripheral blood lymphocytosis (99.5 vs. 60%), or monoclonal gammopathy (1 vs. 30%). A strictly localized tumor (Ann Arbor stage I/IE) was seen in only 1.5% of the LP-IC patients who were successfully treated by local radiotherapy. In all other patients an expectative-palliative treatment concept was pursued. Long-term survival data analysis revealed significant differences between B-CLL and LP-IC and identified the pseudofollicular in B-CLL and the lymphoplasmacytic in LP-IC as the most favorable histological subtypes. The discriminative prognostic potential of clinical stage (Rai or Binet classification) for B-CLL and LP-IC varied and the pattern of prognostic risk factors obtained by multivariate analysis was not identical. Thus, the morphological distinction between B-CLL and LP-IC correlates with characteristic differences between these entities both in their initial clinical presentation and long-term prognosis.

Untreated patients with Hodgkin’s lymphoma in stages I-IIIA with risk factors (large mediastinal mass, massive splenic involvement, extranodal disease) were entered into the HD1 protocol and received a combined chemoradiotherapy [2 × (COPP+ABVD) + 40 Gy extended field irradiation (EF) vs 2 × (COPP+ABVD) + 20 Gy EF]. Patients in stages IIIB/IV (HD3 protocol) received induction chemotherapy [3 × (COPP+ABVD)] and were randomized into consolidation by radiotherapy [20 Gy involved field irradiation (IF)] vs chemotherapy [1 × (COPP+ABVD)]. Seventy-three of 89 evaluable patients (82%) treated according to the HD1 protocol achieved a complete remission. Freedom from progression and survival of patients in stages I-IIIA with risk factors treated according to HD1 were no worse than those of patients in stages I and II without risk factors who received only radiotherapy. Eighty-six of 137 patients (63%) treated according to the HD3 protocol achieved complete remission after induction chemotherapy with COPP+ABVD. This is significantly better than the 31% complete remission rate observed in a previous pilot study with COPP alone (P < 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 × CEVD in case of persisting disseminated disease), a total of 76% complete remissions in stages IIIB/IVAB were achieved. A high erythrocyte sedimentation rate (> 80 mm h−1) was the most significant risk factor for achieving freedom from progression.

Durch die Kiel-Klassifikation wurde eine Neuordnung der Non-Hodgkin-Lymphome in distinkte, auch klinisch-prognostisch differenzier-bare Lymphom-Entitäten erreicht. Im Vergleich zu früheren Klassifikationen grenzt dieses Einteilungsschema zusätzliche Lymphom-Typen (z.B. CC-Lymphom, LP-Immunozytom) (Abkürzungen s. Text) ab, denen wiederum gesonderte klinische Krankheitsbilder ent-sprechen. Im Rahmen einer multizentrischen prospektiven Beobachtungsstudie (Rekrutierung von 1127 unbehandelten Patienten von 1975 bis 1980; Nachbeobachtungsphase bis 1985) wurden eine genauere Definition des klinischen Bildes der einzelnen Lymphom-Entitäten (u.a. Häufigkeit, Alters- und Geschlechtsverteilung, Befalls- und Ausbreitungsmuster) erarbeitet sowie der Erfolg radio-und/oder chemotherapeutischer Maßnahmen überprüft. In der Gruppe der NHL von niedrigem Malignitätsgrad (69,4% der Fälle) lag initial das streng lokalisierte Stadium I/IE der Ann-Arbor-Klassifi-kation bei 1,5-8%, in der Gruppe der hochmalignen NHL (30,2% der Fälle) bei 8-17% der Patienten vor. Durch alleinige lokoregionale Radiotherapie konnte bei 86-89% (CB- und IB-Lymphome) bzw. 100% (LP-Immunozytom, CB-CC- und CC-Lymphome) dieser Patienten eine Vollremission erreicht werden; lediglich die CC- und IB-Lymphome ließen ein relevantes Rezidivrisiko (40 bzw. 50%) erkennen. Eine totallymphatische Radiotherapie führte im Stadium III des CB-CC-Lymphoms noch in etwa der Hälfte der Fälle zu anhaltenden Vollremissionen. Die Überlebenswahrscheinlichkeiten der mit verschiedenen Formen der Chemotherapie behandelten Patienten in den initialen Stadien III und IV spiegeln grundsätzliche prognostische Merkmale der einzelnen Lymphom-Entitäten wider. So weist der kontinuierliche Abfall der Überlebenskurven bei den NHL von niedrigem Malignitätsgrad auf die unabhängig von den bisherigen Therapiestrategien langfristig geringe Beeinflußbarkeit dieser Erkrankungen hin. Bei den hochmalignen NHL unterstreicht der initial steile Abfall der Überlebenskurven mit nachfolgender Plateaubildung die Bedeutung des Erreichens einer Vollremission und die daraus resultierende Heilungschance. Durch uni- und multivariate Analyse der Daten konnten für die verschiedenen Lymphom-Entitäten charakteristische Muster von Risikofaktoren identifiziert werden.

The Kiel classification of non-Hodgkin lymphomas (NHL) identifies distinct entities by morphological and immunological criteria, subdivided into those of low and high grade malignancy and of B- or T-cell subtype. Numerous clinical studies have proven the clinical and prognostic relevance of this classification scheme although the degree of malignancy alone cannot be automatically equated with prognosis. Thus, histological low grade malignancy correlates with favorable response to therapy in all, but with long term survival only in some clearly defined low grade NHL and final cure is achieved in none of them so far. High grade malignancy corresponds to the aggressive spontaneous course of these NHL but is contrasted with the mostly favorable response to therapy and the chance of cure. The immunological T-cell subtype is clearly associated with an inferior prognosis. Additional biological features of NHL, namely chromosomal aberrations and the status of clonality will contribute to a more differentiated view of NHL and will possibly prove to bear prognostic potential.

The cytotoxic potential of nonleukemic cells found in a leukemic sample can be analyzed.

Thirteen cases of T-cell chronic lymphatic leukemia (T-CLL) (including T-cell prolymphocytic leukemia) are presented. Five subtypes were distinguished according to morphologic and functional parameters of the leukemic cells: prolymphocytic; lymphocytic, small; lymphocytic, Sézary-like; lymphocytic, abundant cytoplasm; lymphocytic, abundant cytoplasm and granules. The subtype can be recognized by light and by electron microscopic investigation. Cytochemistry (APh and ANAE) may be helpful to delimit T-CLL from B-CLL, and acid phosphatase to recognize the subtype characterized by abundant cytoplasm and granules. Membrane marker investigations support the diagnosis of T-type CLL. When functional properties of the leukemic cells were tested, cells of one patient (T-PLL) were shown to help in B-lymphocyte differentiation and Ig-secretion, whilst the cells of a second patient (lymphocytic, abundant cytoplasm and granules) were proven to act as effectors in natural killing and antibody-dependent cytotoxicity. The T-helper lymphocyte nature of some of the leukemic cells was supported by demonstration of the Fc mu-receptor in three cases. In one of these patients, monoclonal IgM was detected in the serum. Response to therapy and prognosis were rather poor in this limited number of patients when compared with B-CLL.

The in vitro lysis of human leukemia cells by human natural killer cells was enhanced by pretreatment of the leukemia cells with two different cytostatic drugs, which by themselves do not cause lysis of the tumor cells within the time limits of the in vitro assay, Actinomycin D induced this higher susceptibility in four of eight leukemic samples, Cisplatin in three of four samples, Using Actinomycin D pretreatment, no enhanced lysis was seen with lymphocytes and PHA-lymphoblast targets from healthy donors nor with leukemia cell lines. Our results indicate that a larger fraction of leukemia cells than previously detectable can be recognized and destroyed by spontaneous killer cells.

Interferon has potent antiviral, anti-proliferative, and immunomodulating properties [9, 10]. Leukocyte and fibroblast interferon have been applied in the treatment of human malignancies. Due to the limited availability of interferon, only small numbers of patients have been treated so far. According to the literature a total of 106 patients with malignant lymphomas have been treated, including five patients with Hodgkin’s disease, 65 patients with multiple myeloma, nine patients with acute lymphatic leukemia, 14 patients with chronic lymphatic leukemia, nine patients with nodular poorly differentiated lymphocytic non-Hodgkin lymphoma, and four patients with diffuse histiocytic non-Hodgkin lymphoma. Eight of the 106 patients achieved complete remission and 56 showed partial regression [1, 2, 4, 5, 7, 8, 12–15].