B lymphocytes with latent EBV infection appearing in long-term bone marrow cultures (HLTBMCs) from haematological patients induce lysis of stromal microenvironment.

Human long-term bone marrow cultures (HLTBMCs) are a valuable in vitro model for studying the role of the haemopoietic microenvironment. Here we report the spontaneous appearance of EBV-positive B cells in 6/40 HLTBMCs from patients with various haematological diseases after 3-5 months of culture. After subcultivation of these cells, a novel type of cell line could be characterized, which displayed surface markers and morphological features typical for EBV transformed B-cell lines. As the deproteinized and ultrafiltrated culture supernatants of these cell lines were found to contain an agent with stroma toxic properties, they were termed SSB lines (stroma-toxic-agent-secreting B-cell lines). This agent also exhibited a colony-inhibitory activity on in vitro myelopoiesis and erythropoiesis. These properties are typical for the two polyamines spermine and spermidine which were detected at elevated levels in the culture supernatants of SSB lines. The hypothesis that latent presence of EBV in bone marrow may induce an increased synthesis of spermine and spermidine, which are known to be associated with malignant haematological diseases and bone marrow aplasia, is discussed.

[A questionnaire suitable for general practice for detection of the health status and quality of life of patients with hemato-oncologic diseases: psychometric properties. The Study G "Quality of Life" of the International Society for Chemo- and Immunotherapy (I.G.C.I.)]. / Ein praxisgerechter Fragebogen zur Erfassung von Gesundheitsqualität und Lebensqualität bei Patienten mit hämato-onkologischen Erkrankungen: psychometrische Eigenschaften. The Study Group "Quatify of Life" of the International Society for Chemo- and Immunotherapy (I.G.C.I.).

In the evaluation of therapeutic measures it is important to consider the consequences of the proposed treatment on the subjective quality of health and the subjective quality of life. Since no adequate instrument existed to provide such assessments, a short, theoretically based questionnaire was developed and psychometrically tested. The construction phase was based on data of 104 adults with haemato-oncological diseases, leading to the design of a questionnaire which was tested using data of a further 292 patients. The validity of the "questionnaire for attitudes towards quality of health and quality of life" was assessed by comparing it with physicians' ratings and by correlation with the results of an extensive questionnaire. The reliability was satisfactory; the questionnaire met with high acceptance by patients, physicians and health care personnel. It complies with the requirements of clinical trials where the objective is to measure quality of health and quality of life.

[Risk-adapted therapy of highly malignant non-Hodgkin's lymphomas with COP-BLAM/IMVP-16: a prospective multicenter study]. / Risiko-adaptierte Therapie hochmaligner Non-Hodgkin Lymphome mit COP-BLAM/IMVP-16: eine prospektive multizentrische Studie.

In a prospective multicenter therapy trial the remission-inducing potential of the COP-BLAM (5 courses) and the possibly not cross-resistant IMVP-16 (2 courses) regimen for advanced diffuse large cell lymphomas were investigated. Inadequately responding patients were switched early after 2-3 courses to the IMVP-16 protocol. Between January 1986 and August 1988 349 previously untreated patients were recruited who fulfilled the entry criteria: age 15-75 (mean 56 years), stage II-IV. A first restaging after 3 courses of chemotherapy was documented for 280 cases, a second restaging following 7 courses of chemotherapy or a final report was available for 221 patients, 130 of which where in CR (59%). These figures include 29 cases who died already during induction-chemotherapy of progressive disease (n = 17) as well as of therapy-related complications in CR (n = 12). Thirty-three patients were switched early to IMVP-16 due to incomplete response at the first restaging; 13 of those achieved CR by the new regimen (39%), 9 achieved a partial remission which was turned into CR by additional radiotherapy in 5 cases. Dose reductions and interval prolongations were necessary at increasing rates with subsequent chemotherapy courses (20-50% of the cycles). Relapses have occurred in 32 patients so far (14 early, 18 after stop of treatment). The median survival was 24 months (n = 309 patients). These data show that this treatment strategy is effective in a large unselected group of patients of relatively high age. However, patients showing only delayed response with this protocol probably need more aggressive regimens to obtain durable remissions.

[Multicenter prospective risk-adapted study on the therapy of non-Hodgkin's lymphomas of high malignancy. Use of COP-BLAM/IMVP-16 and randomized adjuvant radiotherapy--study concept and preliminary results]. / Multizentrische prospektive risikoadaptierte Studie zur Therapie von Non-Hodgkin-Lymphomen hoher Malignität. Einsatz von COP-BLAM/IMVP-16 und randomisierte adjuvante Strahlentherapie-Studienkonzept und vorläufige Ergebnisse.

In a multicenter prospective randomized therapeutic trial in advanced (stage II-IV disease, Ann Arbor classification) high-grade malignant non-Hodgkin's lymphomas (NHL, Kiel classification) a sequential combination of the COP-BLAM (5 cycles) and the IMVP-16 (2 cycles) protocols was employed. Response was first determined after 2-3 cycles. In a response-adapted manner the therapy was immediately switched to IMVP-16 if only a partial remission or no response was obtained as evidenced by the first restaging. The aim of the study is the investigation of the efficiency of this concept to induce stable remissions. In an additional randomized trial, involving all patients reaching complete remissions after chemotherapy (second restaging), the prognostic relevance of adjuvant radiotherapy as compared to therapy-free follow-up is evaluated. Eighty percent of the 191 recruited qualified patients have so far become evaluable. Complete clinical remissions were achieved in 76/148 (51%) of the patients up to the first, in 52/85 (61%) of the patients up to the second restaging. Only in a few cases did the expected toxicity of intensive polychemotherapy reach WHO grade 3-4, including nausea and diarrhea, infections, septic complications, myelotoxicity, and stomatitis. Four of the 29 deaths recorded so far occurred in complete remission due to treatment-related complications, whereas 22/29 (76%) died in progression and 3 of unrelated causes.

Lymphomatoid papulosis: remission following intravenously administered acyclovir.

In a 54-year-old male patient suffering from Hodgkin's disease, lymphomatoid papulosis occurred. Complete clearing of the skin lesions was observed immediately after intravenously administered acyclovir. The patient had numerous relapses of his skin eruption with complete responses after each course of intravenously applied acyclovir. This striking therapeutic effect parallels reports of regression of mycosis fungoides and chronic generalized lymphadenopathy after acyclovir application. The mode of action of acyclovir in these disorders is not known. They all are characterized by involvement of the T cell system, and in all these diseases, a virus etiology has been proved or is suggested. Thus, a specific effect of acyclovir on T lymphocytes or selectively on helper T cells is discussed. Alternatively, the virustatic effect of acyclovir could be responsible for the therapeutic success.

Progress in the management of high risk non-Hodgkin's lymphomas. 10 years of experience of the 3rd Medical Department of Hanusch Hospital, Vienna.

An analysis of 173 cases of non-Hodgkin's lymphoma (NHL) admitted to our hospital from January 1973 to January 1983 is presented. Of the 173 cases, 124 patients suffered from NHL of high grade malignancy according to the Kiel classification (37 centroblastic lymphoma (CB), 30 immunoblastic lymphoma (IB), 43 lymphoblastic lymphoma (LB), 14 NHL high grade malignancy unclassifiable). In addition, 26 patients with secondary high grade malignant NHL were included in the analysis (14 secondary CB, 10 secondary IB, 2 secondary LB). Also investigated were 23 patients with anaplastic centrocytic lymphoma (CC) (20 primary CC, 3 secondary CC), an entity originally classified as low grade malignant lymphoma, but showing a poor outcome and need for aggressive therapy. Symptoms at presentation of all patients are described. Of the 173 patients, 71% had an advanced stage of the disease at the time of diagnosis (Ann Arbor stage III or IV). B-symptoms were observed in 81%. Extranodal involvement, (exceptive bone marrow involvement), determined by clinical examination was seen in 55%. Survival of patients changed significantly after replacing initial radiotherapy with aggressive chemotherapy (P less than 0.001). Improvement of survival statistics was due to the better outcome of patients with localized stages (Ann Arbor stages I and II) as compared to those with generalized disease (P less than 0.002). Prognostic factors influencing survival were elevation of lactic dehydrogenase (P less than 0.0001) and response to therapy (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Leg ulcers in congenital dyserythropoietic anemia]. / Ulcera cruris bei kongenitaler dyserythropoetischer Anämie.

We report on an 18-year-old male patient suffering from leg ulcers due to congenital dyserythropoetic anemia and thrombocytosis. Based on this case, we discuss the importance of hematologic disorders for the development of leg ulcers as well as the pathogenetic mechanisms involved.

[Clinical aspects and therapy of iron deficiency]. / Klinik und Therapie des Eisenmangels.

Iron deficiency and iron deficiency anemias are very common disturbances of the hematopoiesis. Although symptomatology and therapeutic possibilities are well known, one should keep in mind that iron deficiency is a symptom and not a diagnosis. The causes of iron deficiency are iron loss, malabsorption and insufficient supply. The best therapy is peroral treatment with well absorbable preparations, whereby the bioavailability has to be taken into consideration. Only in few cases a parenteral therapy which has more side effects is necessary. A overview about the possible therapy is given.

[Alcohol and changes in the hematopoietic system; an epidemiological contribution to the problem of alcoholic anemia]. / Alkohol und Veränderungen des hämatopoetischen Systems; ein epidemiologischer Beitrag zur Frage der Alkoholanämie.

In the course of the "Vienna Health Study 1979" 1261 males and 1548 females divided into 3 age categories (25, 40 and 60 years), were investigated for serum iron level, RBC, leucocytes, haemoglobin, haematocrit, MCH, MVC, MCHC, GOT, GPT and AP. These parameters were evaluated in correlation to the drinking habits of each proband. Significant correlations were found between alcohol consumption and serum iron (elevation in most cases), RBC (decrease), MCV (elevation) and GOT (elevation).

[Chemotherapy of non-Hodgkin's lymphomas]. / Chemotherapie der Non-Hodgkin-Lymphome.

Guidelines for the treatment of non-Hodgkin's lymphoma are laid down in this paper. Low-grade lymphomas diagnosed at an early stage be cured by adequate extended field radiotherapy, although this is a rare occurrence. Advanced stages are treated only on progression of the disease, whereby these measures can merely be regarded as palliative. Lymphomas of high-grade malignancy should be treated by massive chemotherapy from the very beginning, with additional supportive therapy for any complications which may arise, as necessary. After full remission has been achieved by means of chemotherapy, radiotherapy is applied to the previously worst-affected areas. This strategy aims at cure, as in the case of the acute leukaemias, although it is only very rarely successful. It is becoming increasingly possible to achieve remissions through applying various chemotherapeutic regimens, but the question of optimum maintenance therapy, both with regard to type and duration is still unsettled and urgently requires elucidation.

Lymphoplasmacytic/lymphoplasmacytoid lymphoma: a clinical entity distinct from chronic lymphocytic leukaemia?

Clinical data of 116 patients with chronic lymphocytic leukaemia (CLL) and of 114 patients with lymphoplasmacytic/lymphoplasmacytoid lymphoma (synonym: LP immunocytoma, IC) as diagnosed according to the Kiel classification were compared. This interim evaluation of a prospective multicenter study of the Kiel Lymphoma Study Group characterizes IC the less favorable lymphoma entity as evidenced by a more rapid lymph node enlargement, by a higher incidence of constitutional symptoms and of marked anaemia, and by a higher percentage of patients requiring early treatment. In addition, in IC autoimmune haemolytic anaemia was detected in 11.2% of investigated patients as compared to none of the patients with CLL, and monoclonal gammopathy was disclosed in 34.2% of investigated patients as compared to only three patients with CLL who could be, however, unrecognized cases of IC. Actuarial survival data after a follow-up period of 40 months are in favor of an overall better prognosis of patients with CLL than of patients with IC.

Germinal center cell lymphomas: prognostic significance of their histopathological differentiation.

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.

[Clinical relevance of the Kiel classification of non-Hodgkin's lymphomas (author's transl)]. / Zur klinischen Relevanz der Kieler Klassifikation von Non-Hodgkin-Lymphomen.

The Kiel classification of non-Hodgkin's lymphomas, based on morphological, cytochemical and functional criteria, differentiates between lymphomas of low-grade malignancy and high-grade malignancy, which are themselves subdivided into several distinct entities. The probability of survival, the symptomatology and some important laboratory parameters are described in 138 cases of malignant non-Hodgkin's lymphomas, classified according to the Kiel classification. The results show that this classification has not only prognostic and clinical relevance, but also explains some uncommon clinical courses of malignant lymphomas. It is to be hoped that this classification will also promote further progress in therapy.

[Morphology and index of nucleoli in malignant lymphomas]. / Morphologie und Index der Nukleolen in malignen Lymphomen.

The significance of morphology and the number of lymphocyte nucleoli was evaluated by electronmicroscopic sections of malignant lymphomas. It was not only the number and the size of nucleoli which characterized malignant lymphomas differing in histological respect, but above all the different morphology of the nucleoli. The prognostic significance of the nucleolus can be illustrated, if malignant lymphomas of a low grade malignancy with a preponderance of micronucleoli and a low nucleolar index are compared with a significantly higher nucleolar index and markedly increased macronucleoli. These differences are further supplemented by additional morphological properties of nucleoli in malignant lymphomas.

[A clinical study of the non-Hodgkin's lymphomas according to the Kiel classification (author's transl)]. / Klinik der Nicht-Hodgkin-Lymphome nach der Kieler Klassifikation.

A study of 138 patients with Non-Hodgkin's lymphomas was performed. The results were compared with retro- and prospective investigations of patients of the Kiel lymphoma study group. The aim of the study is to evaluate the value of the Kiel classification for the therapy and prognosis of malignant lymphomas. The malignant lymphomas of low- and high-grade malignancy differ significantly in their biological behaviour. Especially the clinical progress of the disease and the response to therapy are different. The lymphomas of low-grade malignancy may not need any treatment for long periods in some patients. In contrary, patients with lymphomas of high-grade malignancy need an active treatment immediately after the establishment of the diagnosis. In stages I and II radiotherapy is sufficient, in stages III and IV chemotherapeutic regimens are necessary. Each type of malignant lymphoma may be accompanied by leukemia. Most of the malignant lymphomas, particularly the immunocytomas, may produce monoclonal gammopathies, most of them being macroglobulinemias. Thus the macroglobulinemia Waldenström is just a clinical necessary to evaluate the significance of the subtypes of the Kiel classification for the planning of specific treatment.

[Anemias resulting from iron metabolism disorders]. / Anämien durch Störungen im Eisenstoffwechsel.

For the most part iron deficiency, but also disturbances of distribution, transport and utilization of iron, are able to cause anemias. To understand the origin of such anemias, firstly iron metabolism, then the clinical symptomatology as well as the laboratory parameters necessary for diagnosis and finally the usual therapies are described.