[Acute hepatotoxicity with intermediate-dose methotrexate in children with leukemia and non-Hodgkin's lymphoma]. / Akute Hepatotoxizität bei mittelhochdosiertem Methotrexat bei Kindern mit Leukämien und Non-Hodgkin-Lymphomen.

In the period of 1.1.1988 to 1.5.1992 49 children, 28 boys and 21 girls, were treated with 219 MTX infusions. The acute hepatotoxicity was investigated from day--1 to day 5 of treatment duration. 30 patients suffered of a ALL, 6 of a relapse of a ALL, 3 of a ANLL and 10 of a NHL. We studied the MTX dosage and the infusion time. At all patients the determination of the activity of the liver enzymes ASAT, ALAT and GGTP in the serum took place according to the treatment protocol. The increase of enzymes activity correlated with the intensity and kind of hepatocellular damage. Partly the extreme increase of lesion parameters is not the expression of an irreversible cytonecrosis. Beside the ALAT also the GGPT is a sensitive predictor of hepatocellular lesion. The high enzyme activity before the MTX application is a indicator of a preexistent cell damage of the liver. The hepatotoxicity measured in the serum was highly correlated with the AUC.

[Results and experiences with a modified BFM protocol for treatment of recurrences in children with acute lymphoblastic leukemia in East German areas]. / Ergebnisse und Erfahrungen mit einem modifizierten BFM-Protokoll zur Rezidivbehandlung von Kindern mit akuten lymphoblastischen Leukämien (ALL) in den ostdeutschen Ländern.

Between 1988 and 1990, 55 patients with first relapses of acute lymphoblastic leukemia (ALL) were treated with a modified BFM-protocol (ALL REZ I/88). The patients were divided according to time and site of relapse: relapses with bone marrow involvement up to 6 months after stopping front line therapy (group A), relapses with bone marrow involvement beyond 6 month after therapy (group B) and isolated extramedullary relapses at any time (group C). During therapy the patients received alternating courses of polychemotherapy including infusions of intermediate dose methotrexate (1 g/m2 in 36 hours). The maintenance treatment consisted of daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second remission rate was 89% (group A: 90%, group B: 86%, group C: 93%) and the probability of event free survival (EFS) at 4 years is 0.28 +/- 0.13 (group A: 0.22 +/- 0.12, group B: 0.24 +/- 0.18, group C: 0.57 +/- 0.15). We conclude, that with the treatment regimen applied, long lasting second remission can be achieved in about one third of patients even after intensive front line therapy. The most unfavourable prognoses were seen in patients with early bone marrow relapses (group A).

[Experiences with modified BFM protocols in the treatment of children with acute lymphoblastic leukemia (ALL) in East Germany 1981-1991]. / Erfahrungen mit modifizierten BFM-Protokollen bei der Behandlung von Kindern mit akuten lymphoblastischen Leukämien (ALL) in den ostdeutschen Ländern von 1981 bis 1991.

Between September and August 1991 818 previously untreated children and adolescents up to 18 years of age with acute lymphoblastic leukemia were entered into two modified BFM-protocols. Patients with B-ALL were excluded. From 1981 to 1987 524 patients were entered into the randomized multicenter study ALL VII/81 (modified ALL-BFM 81 protocol). Patients were divided into three risk groups standard (SR), medium (MR), high risk (HR) using the BFM risk factor. In a connecting study from 1988 to 1991 294 patients were registered on the stratified and randomized multicentric trial ALL VIII/87 (modified ALL-BFM 86 study). The main modification in study ALL VII/81 concerned the duration of treatment. Patients were randomized into two groups. The first group received as a late reinduction protocol III and then therapy was stopped. The second group received 6-MP and MTX for another six months. The other whole treatment strategy of ALL-BFM 81 was adopted. In protocol ALL VIII/87 the only modification was the reduction of the MTX dosage from 5 g/m2 to 1 g/m2 with an infusion time of 24 hours (leucovorin rescue 15 mg/m2 after 48 and 54 hours). The probability of the event-free-survival (EFS) for study ALL VII/81 was 59%. CNS events were significantly more frequent in standard risk patients with intermediate dose MTX (4 x 0.5 g/m2) compared with the irradiation group (18 Gy). The EFS for SR patients amounts to 61%, for MR patients to 59% and for HR patients to 36%. There was no significant difference of EFS for the two groups with different duration of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Therapy of acute myeloid leukemia in children--results of the AML II/87 multicenter study]. / Therapie der akuten myeloischen Leukämie bei Kindern--Ergebnisse der multizentrischen Therapiestudie AML II/87.

Fifty seven patients entered the cooperative study AML II/87 of the working group "Pediatric Hematology and Oncology" of East Germany. Two patients with initial hyperleukocytosis died prior therapy. 13 patients died within the first 4 weeks of therapy, 3 patients did not respond to therapy, and one patient is not yet in remission. 38 patients (70%) attained a complete remission. 15 patients get a bone marrow transplantation in first CR (10 autologous BMT without purging, 5 allogenous BMT). 12 of them are living and well 3 to 34 months after BMT. 9 of the 23 patients under chemotherapy relapsed, one patient is lost to follow up. 13 patients are living in continuous complete remission. The life table probabilities 48 months after the start of the protocol are 0.43 for disease free survival (DFS) and 0.60 for event free interval (EFI). The respective results of the former protocol AML I/82 were 0.34 for DFS and 0.47 for EFI.

[Rare inflammatory reactions in infants and their correlation with pathomorphologic alterations of the immune system]. / Seltene Entzündungsreaktionen im Kindesalter und ihre Korrelation mit pathomorphologischen Befunden am Immunsystem.

Autopsy-findings in infants with rare inflammatory disorders or infectious diseases esp. opportunistic infections may suggest defects of the unspecific and specific defence. The histopathological appearances of different lesions were correlated with possible underlying alterations or generalized defects of the immune system.

[Severe aplastic anemia: indications and limits of biological immunosuppression]. / Schwere aplastische Anämie--Indikationen und Grenzen der biologischen Immunsuppression.

Diagnostic criteria++ and differential therapy of SAA are characterized. A record of ATG/ALG-present modus is demonstrated. The immunosuppressive combination therapy with ALG + Cyclosporin A + MTP represents a prospect.

[Frequency distribution of DNA in blood and bone marrow cells of children with acute non-lymphatic leukemia using impulse cytophotometry]. / Untersuchungen der DNS-Häufigkeitsverteilung in Blut- und Knochenmarkzellen von Kindern mit akuter nichtlymphatischer Leukämie mittels Impulszytophotometrie.

1. As compared with the peripheral blood lymphocytes of healthy subjects the cells in the mononuclear fraction of peripheral blood and in the bone marrow of children with ANLL show a significant higher S- and G2 + M-phase. 2. A high proliferative activity correlate with a bad prognosis or with reaching no haematological remission. 3. Frequently, aneuploid cell populations will occur in the morphological subtypes M 4 and M 5.

[Impulse cytophotometry studies of bone marrow and blood cells in children with acute lymphoblastic leukemia (ALL). 2. Lymphatic cells in blood]. / Impulszytophotometrische Untersuchungen von Knochenmark- und Blutzellen bei Kindern mit akuter lymphoblastischer Leukämie (ALL). 2. Mitteilung: Lymphatische Zellen des Blutes.

The DNA-content of mononuclear cells of the peripheral blood of infantile and juvenile ALL patients was investigated using Pulse Cytophotometry. The fraction of cells in S- and G2 + M-phase is significantly increased in comparison with samples of healthy probands. The fraction of DNA-synthesising cells (S-phase) of both peripheral blood (mononuclear cells) and bone marrow of leukemia patients cannot be significantly distinguished by mathematical methods. On the other hand, the fraction of cells in later phases of cell cycle (G2 + M-phase) is significant enhanced in the bone marrow in comparison with the peripheral blood. A high correlation was found between the number of leukocytes and fraction of G2 + M-phase cells in the peripheral blood of SR- and MR-patients. No correlation was found between the number of leukocytes and S-phase-fraction. The occurrence of aneuploid cell populations in the mononuclear fraction of peripheral blood in the acute state of ALL could be of importance for prognosis and regime of therapy.

[Impulse cytophotometric studies of bone marrow and blood cells in children with acute lymphoblastic leukemia (ALL). 1. Bone marrow cells]. / Impulszytophotometrische Untersuchungen von Knochenmarkund Blutzellen bei Kindern mit akuter lymphoblastischer Leukämie (ALL). 1. Mitteilung: Knochenmarkzellen.

1. Compared with the peripheral blood lymphocytes of healthy children the cell fractions in the S- and G2 + M-phase are significantly higher in the bone-marrow of those children affected with ALL. This increase was proved in the SR- and MR-group irrespective of the cytomorphological subtype and cytochemical reaction. In patients with relapses the percentage of S-phase cells is below 6%. 2. In about 30% of our patients (mainly in the SR-group with L1-morphology) an initial DNA-aneuploidy was identified. As the risk of relapse is higher in children without DNA-aneuploidy, this symptom has a pretherapeutical-prognostic significance. 3. In the phase of hematological full remission, DNA-frequency distribution correlates with the proliferative activity of normal hematopoiesis. It provides no additional information about the pretherapeutical risk.

Improved treatment results in childhood acute nonlymphoblastic leukemia with the BFM-AML protocol 78 in a multicenter study in the GDR.

Eighty-seven children with acute nonlymphoblastic leukemia were treated with the AML protocol BFM 78 between June 1979 and February 1986 in a multicenter study in the GDR. Seventeen children (20%) died from early complications, eight did not respond to therapy. Fifty-eight patients (70%) achieved a complete remission. Twenty-three patients relapsed. The life table analysis revealed after 5 years a probability for event-free survival of 36% (SD = 6%) and an event-free interval of 51% (SD = 8%). Six patients were transplanted in first remission. Two of them died; one (M 1) on day + 19 from encephalopathy and one (M 4) on day + 60 from acute GVHD. The overall results are in good correlation with the original BFM study, but there are differences in the subtypes. Results are superior to other AML protocols in our group.

[Suppression of lymphocyte proliferation in the blood of children with infectious mononucleosis. Flow cytometry study]. / Uber das Proliferationsverhalten von lymphatischen Zellen des Blutes bei Kindern mit infektiöser Mononukleose. Untersuchungen mit dem Impulszytophotometer.

The investigation of lymphatic cells from venous blood shows an increase of cells in the S-phase during the acute stage of infectious mononucleosis, which is connected with a decrease of G1-phase cells. G2 + M fraction will remain within the normal range. These changes will completely recede within the first four weeks of the disease. In contrast to that, there is an increase in the percentage of G2 + M phase cells in the bone-marrow at the onset of the disease. The other fractions are within the normal range.

[Side effects of therapy with antihuman lymphocyte globulin]. / Nebenwirkungen der Therapie mit Anti-Humanlymphozyten-Globulin (AHLG).

The most important side effects during AHLG-treatment of 34 children suffering from juvenile chronic arthritis, collagenoses, autoimmune chronic hepatitis, aplastic anaemia and acute lymphoblastic leukemia are: Thrombocytopenia, urticaria, fever, anaphylactic reaction. They all are reversible a short time after cessation of AHLG-administration.

[Bone marrow cytology in diseases of autoimmune pathogenesis in childhood and its changes during therapy with anti-human lymphocyte globulin (AHLG)]. / Das Knochenmarkzellbild bei Krankheiten mit Autoimmunpathogenese im Kindesalter und seine Veränderungen unter der Therapie mit Anti-Humanlymphozyten-Globulin (AHLG).

Among the organs of the immune system the bone marrow is comparably simple accessible. Autoimmune diseases are characterized by reactive cytomorphological symptoms. Due to own investigations the granulo-erythropoietic index (G/E-index Rohr) as a parameter of inflammatory activity as well as the amount of plasma cells as an indication of humoral reactivity are described--before and under treatment with anti-human lymphocyte globulin.

[Clinical effects of anti-human lymphocyte globulin in the treatment of collagenoses in childhood]. / Klinische Effekte von Anti-Human-Lymphozyten-Globulin (AHLG) bei der Behandlung von Kollagenosen im Kindesalter.

9 children with collagenoses were first treated with AHLG "Dessau" in combination with corticosteroids and then with Imurek (azathioprine). The children seemed to be vitally endangered and suffered from panarteritis, dermatomyositis, polyserositis or corticosteroid-resistent systemic juvenile rheumatoid arthritis. As assessed by decrease of inflammation and clinical symptoms the treatment appeared in one case to be very good and in another good; in four other children it was good for a short period; in three children there was no effect at all. Side effects occurred relatively frequently (thrombocytopenia, anaphylactoid reactions). The justification of an immuno-suppressive treatment together with anti-human-lymphocyte-globulin is discussed in relation to todays knowledge of the pathogenesis of collagenoses and of the mechanisms behind the effects of the AHLG.