Association of hepatitis C virus infection with chronic liver disease in paediatric cancer patients.

A total of 203 paediatric cancer treatment survivors were tested for serum antibodies against hepatitis-C virus (anti-HCV). Anti-HCV was detected in 41 patients (20.2%) with first generation anti-HCV ELISA. Positive results were confirmed in all samples retested with a second generation ELISA (n = 35) and in all but two cases re-analysed by immunoblotting (n = 23). Anti-HCV positive children had received significantly more blood product transfusions compared to seronegative patients. In 75 children (32%) chronic liver disease was found. It was defined as an elevation of serum alanine aminotransferase values to a least 2.5 times the upper limit of normal persisting for 6 months or longer. Hepatitis A was never detected, and in 58 children the chronic hepatopathy was unexplained by hepatitis B (non-A non-B chronic liver disease). Of these patients 29 (50%) were seropositive for anti-HCV. Surprisingly, non-A/non-B chronic liver disease was associated with anti-HCV in 14 of 19 solid tumour patients (78.9%), but in no more than 14 of 39 leukaemia and lymphoma patients (35.9%). This phenomenon was not explained by different rates of cytomegalovirus disease and drug toxicity related hepatopathies between the two groups. It may be related to differences of leukaemia/lymphoma compared to solid tumour therapy schedules (differential immunosuppression and liver toxicity).

[Autologous peripheral stem cell transplantation in children]. / Autologe periphere Stammzelltransplantation im Kindesalter.

19 children between 3 and 23 years underwent 79 leukapheres for collection of blood stem cells. In children suffering from acute lymphoblastic leukemia (ALL), Non Hodgkin's Lymphoma (NHL) and Ewing's Sarcoma (ES) we collected 6.87 x 10(4) CFU-GM/kg (range 2,65-21.7), if collections were started with the first platelet rise. In children with peripheral primitive neuroectodermal tumors (PNET) and neuroblastoma (NBL) we gained only 1.20 x 10(4) CFU-GM/kg (range 0.09-2.24). 17 children received high dose chemoradiotherapy and peripheral stem cell +/- bone marrow rescue. 9 suffered from solid tumors, 8 from hematopoietic malignancies. 9 were transfused with peripheral stem cells only, 8 received bone marrow in addition. Time to reach 0.5 x 10(9)/l granulocytes was very short-median 31 days (12-65), in 4 children receiving more than 5 x 10(4) CFU-GM/kg 12 to 13 days, only. On January 31st, 1989 6/17 children are alive in complete remission after a median observation time of 14.5 months (3-26) after autologous stem cell transfusion, one child is alive in "no remission", 7 died with relapse, 3 died because of infections (2 x aspergillosis, 1 x pseudomonas septicemia). The collection of blood derived stem cells by leukaphereses was well tolerated even in very small children and easily repeatable. With optimal timing high stem cell numbers were obtainable, resulting in a very short duration of posttransplant granulocytopenia.

[3 cases of eosinophilic leukemia with atypical granulation in the eosinophils and neutrophils]. / Dre Fälle von Eosinophilenleukämie mit atypischer Granulation in Eosinophilen und Neutrophilen

Three patients with eosinophilic leukemia and atypical granulation in the eosinophils are described. A remarkable light and electron microscopic finding was the appearance of enormous granules in the neurtophils and eosinophils. In addition the usual anomalies seen in acute leukemia, for example asynchronisation in cell maturation, fibrillar bundles, shrinkage of nucleolus and cell organelles, signs of degeneration and also the auer-rods characteristic of AML are observed.

Immunological follow-up of acute lymphoblastic leukaemia.

In different treatment groups of children with acute lymphatic leukaemia and undifferentiated leukaemia, the lymphocyte count and a number of immunologic parameters were examined during the various stages of treatment. These parameters were related to the type of chemotherapy as well as the stages of treatment. This paper deals with the values of lymphocyte counts, of gamma globulin, IgG, IgM and IgA and the results of the DNCB skin tests, as a parameter for cellular immunity. IgG determined by acetate sheet electrophoresis showed no significnat change, while its significant reduction was shown during the periods of prophylactic reinduction with vincristine in the Pinkel VII scheme, The IgM level was significantly raised in the initial stage before treatment and in all periods of treatment both in the Pinkel VII group and in an earlier therapeutic group treated with methotrexate every two weeks and vincristine pulses every six weeks. IgA was raised in both groups before treatment but significantly reduced during the phases of maintenance and reinduction. About 50% of the P VII cases had negative DNCB skin tests during maintenance therapy, while all long-term survivors in the earlier methotrexate group had a positive skin test.

[Responsiveness of lymphocytes to stimulation by pha and autologous blasts in acute lymphatic leukemias during remission (author's transl)]. / Stimulierbarkeit der Lymphozyten bei akuter lymphatischer Leukämie im Remissionsstadium durch PHA- und autologe Blasten

The paper deals with the question how far the lymphocytes of acute lymphatic leukemia patients in remission can be stimulated by PHA and autologous blasts in the MLC-Test. The lymphocyte stimulation by PHA showed considerable variation dependent on the phase of therapy. A significant reduction of the responsiveness to PHA stimulation was found during the prophylactic reinduction treatment with Vincristin and Prednisolon compared with the results during maintenance therapy. The examination of lymphocyte stimulation by conserved autologous blasts in the mixed lymphocyte culture-test yielded positive results in one of three children at the beginning of remission and in 2 of 3 children during the consolidated remission period.

Prevention of meningeal leukaemia and relapses by cranial irradiation and intrathecal MTX in acute lymphatic leukaemia.

Experience with CNS prophylaxis in 35 children with acute lymphatic leukaemia is reported. Before prophylactic irradiation of the skull was given the average survival time in 36 children was 2,8 (2,7) years. Menigeal leukaemia preceeded bone marrow relapse in 9 cases and followed relapse in a further 5 cases (39%). Between 1971 and 1973 Pinkel's treatment scheme VII was given to 35 children. This included prophylactic skull irradiation and intraspinal MTX injections. 29 children are still in their first remissions which range from 10 - 35 months in length. Meningeal leukaemia has not so far been observed, in this latter group.

[Spontaneous radial segmentation of the nuclei of myeloblasts in a case of chronic granulocytic leukemia during blastic crisis. an electromicroscopical study (author's transl)]. / Spontane radialsegmentation de myeloblastenkerne einer chronis"h-myeloischen leukämie im blastenschub eine elektronenmikroskopische studie

By means of electron microscopy, myeloblasts with spontaneous radial segmentation of the nuclei from a patient with micromegakaryotic chronic myelosis in the blastic crisis were analysed. The centriol was found in the center of the cells and microtubules were found between the segments of the nucleus. These observations support the hypothesis that spontaneous radial segmentations of the nuclei of tumor cells is associated with a contractile process of the microtubules with split the nucleus.

[The use of the cell separator in the treatment of leukemia]. / Der Einsatz des Zellseparators in der Leukämiebehandlung

In order to provide leukemic patients during the critical granulocytopenic stage with a sufficient amount of granulocytes a blood cell separator with a continuous extracorporeal circulation was developed. This permits to obtain up to 3.0-10(10) leukocytes during a 4---5 hours period from a single donor. According to our own experiences with 20 leukophereses performed in 13 healthy donors by the use of the AMINCO cell separator an average of 1.17-10(10) leukocytes with a granulocytic portion of 61% was collected per run. In two cases of agranulocytosis and septic fever (one case of pseudomonas septicaemia) the repeated administration of leukocyte concentrates, while specific antibiotic therapy was continued, led to a marked improvement over a longer period of time. Furthermore thrombocyte concentrates up to 7.0-10(10) platelets can be obtained by the cell separator. Applied as depletory method in the treatment of CML and CLL leukopheresis may rapidly diminish the peripheral leucocyte count while spleen and lymphomas decrease in size at the same time. A 20% reduction in cell count may be achieved by a serie of 3---4 leukophereses. Also the use of the cell separator in the treatment of makroglobulinemia by plasmapheresis is discussed.

[Immunologic parameters in acute lymphatic leukemias in the course of different types of chemotherapy (author's transl)]. / Immunologische parameter bei akuten lymphatisechen Leukämien während verschiedener Chemotherapieschemen

In 2 groups of patients under treatment with acute lymphatic leukemia and undifferentiated leukemia, apart from the lymphocyte count, a number of immunologic parameters were examined during the various stages of treatment. These parameters were related to the type of chemotherapy as well as the stages of treatment. This paper deals with the values of lymphocyte counts, of gammaglobulin, IgG, IgM and IgA and the results of the DNCB skin-tests, as a parameter for cellular immunity. The determination of gammaglobulin using the acetate sheet electrophoreses, showed no significant change. However a significant reduction of the IgG was shown during the periods of prophylactic reinduction with Vincristin in the Pinkel VII scheme. IgM quantities were significantly raised in the initial stage before treatment and in all periodes of treatment both in the Pinkel VII group and in an earlier therapeutic group with methotrexate two weekly and Vincristin pulses every 6 weeks. IgA was raised in both groups before treatment but significantly reduced during maintenance and reinduction phases. About 50% of the P VII cases had negative DNCB skintests during maintenance therapy, while all long term survivors in the earlier methotrexate treatment group had positive skintests. The 2 following papers deal with the results of PHA stimulation and the B and T cell determinations.

Clinical trials with bis-dioxopiperazine propane (ICRF 159; NSC 129, 943) in acute leukaemias.

Clinical experience is reported with bis-dioxopiperazine propane (ICRF 159) in 20 children with acute leukaemia in relapse. They were resistant to most of the generally used cytotoxic drugs. Despite the unfavourable selection of cases, two complete and seven incomplete remissions lasting from 1 to 6 months were obtained.