[Successful combination therapy of a metastatic Triton tumor in a 5-year-old boy]. / Erfolgreiche Kombinationstherapie eines metastasierten Tritontumors bei einem 5jährigen Jungen.

A 5-year-old boy with a metastatic Triton tumor was treated with resection, local irradiation and an additional combination chemotherapy including Ifosfamide. One year after completion of the treatment the boy is now without a tumor and in excellent condition.

[Life-threatening hyperuricemia during cytostatic leukemia therapy]. / Lebensbedrohliche Hyperurikämie bei zytostatischer Leukämie-Therapie.

In 25 children with lymphoblastic leukemia is shown that prophylactic treatment with allopurinol, 48 hours before initial cytostatic therapy, always prevents hyperuricemia. In 4 patients was renounced on this measurement and 2 of 4 patients died of the sequeles of hyperuricemia. In severe ill leukemic patients the parental use of allopurinol is recommended. 2 additional patients developed during remission therapy or after cessation of chemotherapy a moderate hyperuricemia which had to be treated, over years, with allopurinol.

Binding of lectins to leukemic cell lines.

The binding of 12 different fluorescein-conjugated lectins to 10 ALL (acute lymphoblastic leukemia) cell lines and two cell lines derived from patients in blast crisis of myeloid leukemia was examined. The specificity of the membrane fluorescence was demonstrated by inhibition with various saccharides. Three of the lectins bound to all cell lines, four bound to only some of the lines, and five were not bound. There was no correlation between the binding pattern and the immunological phenotype of the cultured lymphoblasts. The lectin from Lens culinaris, however, in the experimental condition used (incubation at 4 degrees C, fluorescein conjugation at pH 8.5), bound only to the cell membranes of 'Ia-like antigen, positive cell lines. Although three lectins (Lens culinaris, Pisum sativum, concanavalin A) had an identical monosaccharide specificity, they bound to different cell lines. Membrane fluorescence with the lectins from Helix pomatia, Arachis hypogea, and Ricinus communis (MW 60,000) was achieved after treatment with neuraminidase. It was shown that binding of the lectins from Helix pomatia and Ricinus communis 60 was effected by enzymatically exposed glycoproteins, whereas the lectin Arachis hypogea was bound via neuraminidase which stuck to the cell membrane.

[Prognostic factors in acute lymphoblastic leukaemia--with special consideration of pre-diagnostic duration of signs (author's transl)]. / Prognostische Faktoren bei der akuten Lymphoblastenleukämie--unter besonderer Berücksichtigung der prädiagnostischen Symptomendauer.

It is concluded from the prognostic factors of acute lymphoblastic leukaemia, as far as they have become known up to now, such as initial leukocyte count, extent of organ infiltration, etc, that the pre-diagnostic duration of signs, representing a measure of the proliferation activity of the leukaemia cells, could also represent a relevant prognostic characteristic. A check conducted in 90 children treated between 1966--1975 yields a correlation only between a very short pre-diagnostic duration of signs (less than 2 weeks) and the duration of the first complete remission (as well as the survival time). However, even those prognostic factors which are already generally recognised, possess merely limited reliability, because they do not take the individual response to therapy into account. Hence, improvement of prognosis of the course of the disease can be expected only if the continuous decrease of the remaining population of blasts during the early phase of remission can be determined with greater accuracy than before.

[Monitoring of remission quality in acute leukemia of childhood by repeated determinations of B-cell-allo-antigen on lymphoblasts (author's transl)]. / Der Nachweis des B-Zell-allo-antigens auf Lymphoblasten zur Bestimmung der hämatologischen Remissionsqualität einer akuten kindlichen Leukämie.

B-Cell-allo-antigen was demonstrated on lymphoblasts of children with acute lymphoblastic leukemia and on 14 permanent growing lymphoblastoid cell-lines. Pooled sera of 4 selected multiparas and a rabbit antiserum were used as specific antisera. Antigen was more effectively detected with heterologous antibodies than with human antisera. Primary lymphoblasts were characterized by B-cell-allo-antigen and lack of membrane immunoglobulins and Fc-receptors on the same cell. The quality of remission, i.e. the early diagnosis of relapse was better surveyed by immunological characterization than by cytological assessment. The bone marrow was examined in 8 patients with initial leukemia, in 13 patients with partial remission and in 30 patients in complete hematological remission. A striking discrepancy between immunological and cytological examination was observed in the bone marrow 4 weeks after inital anti-leukemic chemotherapy. At that time an increased number of blast-typed cells could still be counted in the immunological evaluation, although the cytological evaluation revealed already a complete hematological remission.

Effect of gammaglobulin injection on circulating immune complexes in various diseases.

Immune complexes (ICs) participate in the pathogenesis of various diseases and can be shown in 18% of all hospitalized patients (excluding those with infectious diseases) by means of a sensitive method such as the Raji-cell radioimmune assay. However, before this test can be applied to quantify disease activity in renal, connective tissue and neoplastic diseases, it must be recognized that febrile infections of the upper respiratory tract also induce ICs in 86% of all patients. The immune complexes containing microbial antigens can be reduced or removed by a single injection of human immunoglobulin. This is a simple method to distinguish between the immune complexes of different specifities. The resulting removal of some immune complexes may be the explanation for the claimed therapeutic effect of gammaglobulin injection in normogammaglobulinemic patients.

[Establishment of leukaemia cell lines and their significance for clinical and experimental oncology (author's transl)]. / Etablierung von Leukämiezellinien und ihre Bedeutung für die klinische und experimentelle Onkologie.

Permanent in vitro growing leukemic cell lines have been established from all types of immunologically classified childhood leukemias. Essential characteristics of primary blasts and cultured cells are identical. In contrast to lymphoblastoid, non-leukemic cell lines, the Epstein-Barr-virus specific nuclear angiten (EBNA) is not detected. Up to now 8 Non-B-non-T cell lines (6 of them were derived from children with acute lymphoblastic leukemia, 2 from patients with chronic myeloid leukemia), 8 T-lines and one B-line have been established. Three Non-B-non-T lines from children with acute lymphoblastic leukemia (KM-3, RU-3, MH-3) and one T-cell line (JM) were cultivated by ourselves. Cultured blasts represent a pure tumor material which can be propagated in large quantities. Leukemic cell lines reveal a new approach for the search after leukemia-associated proteins and represent another possibility for the experimental investigation of the etiology of leukemia.

[Determination of pregnancy-associated glycoprotein for diagnosis and control of tumours in childhood]. / Bestimmungen des Alpha-2-schwangerschaftsassoziierten Glykoproteins zur Diagnostik und Verlaufskontrolle von Tumoren im Kindesalter.

Of 31 patients with solid, malignant tumours, 15 were shown to have over 0.5 mg/100 ml Serum concentration of alpha-2 pregnancy-associated glycoprotein (alpha2-PAG). These increased values were found for patients with neuroblastomas, Wilms tumours and rhabdomyosarcomas. However, for several different lymphomas and haemoblastoses, alpha2-PAG could not be demonstrated with the electroimmunodiffusion technique used (Laurell). From 230 children with non-neoplastic diseases, 62 had demonstrable concentrations of alpha2-PAG, of 38 healthy children, 2 were positive, while from 50 newborn infants, with different illnesses no increased values were found. Post-operative controls using repeated determination of d2-PAG are complicated by the slow change in concentration, and by the influence of chemotherapy. The determination of alpha2-PAG for the initial diagnosis of malignant diseases in childhood and for post-operative monitoring of the disease, is therefore of only limited value at least until further investigations have been carried out.

BK virus: II. Serologic studies in children with congenital disease and patients with malignant tumors and immunodeficiencies.

Sera of 451 children with congenital diseases and 185 tumor patients were tested for BK virus-specific antibodies by hemagglutination inhibition and IgM-immunofluorescence tests. Compared to age-matched control groups, higher percentages and significantly elevated geometric mean titers of HI antibodies were found in all patient groups tested. Of children under six months of age with congenital diseases such as dysplasia, cerebral defects, and hyperbilirubinemia and hepatosplenomegaly, 4.2% (17/402) had BK virus-specific IgM antibodies. No positive sera were found in 68 control sera. Of tumor patients 5--15 years of age, 8.6% (16/185) had IgM antibodies to BK virus. In the control group, 30% (3/99) had them. Serial serum samples from 76 tumor patients treated with cytostatic drugs showed seroconversion in three cases. No relationship between certain clinical features and BK virus infection was noted. Isolation of BK virus was successful from urines of two infants with connatal defects, six patients suffering from malignant tumors, and four patients with inherited immunodeficiencies.

Cranial computerized tomography in children with lymphoid malignancy and seizures.

Focal and generalized seizures occurred in 4 patients with acute lymphoblastic leukemia and non-Hodgkin-lymphoma. The etiology of the neurological complications could be established by cranial computerized tomography (CT): i.e., 1. localized metastasis with calcification and 2. acute intracerebral hemorrhage during induction therapy in two patients with malignant lymphomas; 3. diffuse cerebral infiltration with blast cells and 4. cerebral atrophy in two children with acute lymphoblastic leukemia who were in relapse. Accurate diagnosis of cerebral complications in hemoblastoses is essential for appropriate therapy and CT may lead to more effective treatment in patients with lymphoid malignancy and seizures.

[Immunological diagnosis of leukemias in childhood (author's transl)]. / Immundiagnostik der Leukämien im Kindesalter.

Subclassification of leukemias in childhood by cytochemical methods or blast size is arbitrary to some extent. The increased knowledge of physiological development of hematopoetic cells allows to classify these diseases according to the degree of differentiation of the cells involved. Immunological cell-membrane structures are used as for markers differentiation. In this way, 4 types of lymphoblastic leukemias and 5 types of myeloid leukemias can be diagnosed. This classification can help to answer clinical and theoretically important questions. In ALL and during the blast crisis of CML, new groups with increased risk are defined, important for the choise of initial therapy, and evaluation of therapeutic trials. The immunological markers can help to detect already small numbers of blasts at the beginning of a hematological relapse. Transformations of the blast type during the course of the disease can be explained. Experiments in animals indicate that an immunological classification of leukemias correlates with differences in pathogenesis and etiology.

[Early detection of abdominal tumours in preventive medicine in childhood (author's transl)]. / Früherkennung von Bauchtumoren im Rahmen der Kindervorsorge.

Out of 51 abdominal tumours diagnosed in the age group subject to preventive screening eight tumours were detected during preventive investigations. Children up to one year were mainly involved. The additional investigation at 6-7 months and careful palpation of the abdomen and further investigations following questionable results lead to the assumption that the rate of early diagnosis of abdominal tumours at preventive investigations in childhood may still be improved. The importance of early diagnosis suggests that the disease group should be included in the code catalogue of diseases which should be actively sought in preventive medicine.

Isoenzyme pattern of alkaline phosphatase in the serum of children with leukaemia after long-term chemotherapy.

Chemotherapy was discontinued in thirteen children with acute lymphoblastic leukaemia after 2-3 years without relapse. In the following months, a continuous increase was observed in the serum alkaline phosphatase. A maximum was reached at different times but all patients had normal values again after 19 months. The rise in the total activity is due to an isolated increase of the bone isoenzyme. Increased enzyme activity in this post-therapy phase of the disease does not signify liver damage from the preceding chemotherapy, but rather is due to an increased osteoblast activity associated with a temporary increase in growth rate.

[Immunological membrane markers in blasts and lymphocytes of patients with acute leukemia]. / Immunologische Membranmerkmale auf Blasten und Lymphozyten von Patienten mit akuter Leukämie.

Acute lymphoblastic leukemia can be subdivided into groups with different prognoses and clinical courses by immunological cell-markers. Patients with blasts, expressing T-cell-markers in a high density (T-cell leukemia), had an increased incidence of meningeal relapses, tumor formation in abdomen or mediastinum. T-lymphoblastic lymphoma is the same disease only different in initial presentation. After combination chemotherapy over one year, lymphocytes populations with no immunological cell-markers are relatively increased. Regular monitoring of the immunological subgroups of lymphocytes seems to be unhelpful in early diagnosis of periods with increased risk of severe infections.

[Unusual complications in the course of histiocytosis X (author's transl)]. / Ungewöhnliche Komplikationen im Verlauf der Histiocytose X.

In 3 patients with histiocytosis X the following complications are described: 1. A 16 year old boy suffered from generalized histiocytosis in infancy. He died after acute intracranial hypertension caused by a basilar impression. 2. Recurrent spontaneous pneumothoraces was the first symptom of an initial exclusively pulmonary histiocytosis X. 3. Exophytically growing soft tissue tumors in the late disease state of a progressive histiocytosis X.

Characterization of EBV-genome negative "null" and "T" cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non-Hodgkin lymphoma.

Sixty-two explants from peripheral blood, bone marrow and cerebral fluid of children with acute lymphoblastic leukemia (ALL) and leukemic transformed non-Hodgkin lymphoma (NHL) were cultivated for at least 8 weeks. Although lymphatic cells persisted up to 16 weeks in tissue culture, no proliferation was observed in 54 cultures. From the remaining cultures, eight permanently growing cell lines were obtained. Five of these were EBNA (Epstein-Barr virus-specific nuclear antigen)-positive. Three, however, were ENBA-negative and lacked Epstein-Barr virus genomes. Two cell lines (KM-3 and SH-2) expressed neither B nor T cell characteristics. One line (JM) expressed T cell characteristics and complement receptors. The growing lymphatic cells represented leukemic cells, since the pattern of cytochemical staining and that of membrane receptors of lymphoblasts from the same donor prior to cultivation were identical. All leukemic cell lines were derived from patients in relapse. In contrast, no proliferation of leukemic cells occurred in explains from patients revealing the first manifestation of the disease. These results suggest enhanced growth potential of lymphoblasts resisting antileukemic therapy.