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Biomedical subjects

G Janka

Publications and source records attributed to G Janka.

36 records · Page 2Linked to original sources

[Initial treatment of acute childhood leukemia with extreme leukocytosis by blood exchange transfusion -- rheological aspects (author's transl)].

In leukemia patients with extremely high leukocytosis the great number of poorly deformable lymphoblasts compared to normally deformable red cells greatly influences the flow properties of leukemic blood. The increased blood viscosity implies a great risk of disturbance of the microcirculation by leukostasis and bleeding. Removal of large amounts of leukemic cells by exchange transfusion with fresh blood diminished leukemic cell burden and reduced the initial elevated leukocyte counts by more than 50% in 3 patients. In addition, anemia and thrombocytopenia improved and the disturbed plasma coagulation returned to normal. One of the patients with additional risk factors treated by exchange transfusion died 8 months after diagnosis in hematologic release. The two other patients perform well without relapse six and nine months after diagnosis, respectively. Exchange transfusion with 150 ml/kg of fresh blood is considered to be of value to avoid severe early complications as e.g. massive intracerebral hemorrhage observed in 3 other patients and to correct hematological and rheological abnormalities in childhood leukemia with extreme leukocytosis. Possible favourable effects as to long term prognosis have to be awaited.

Blood Viscosity↗

Antibody incubation of human marrow graft for prevention graft versus host disease.

An in vitro incubation of incompatible donor bone marrow by xenogenic anti-T-cell globulin (ATG) suppressed an otherwise lethal GvH reaction in animal models. An application of this principle to clinical bone marrow transplantation was successfully tried in three patients with acute lymphoblastic leukemia. Preparation of the specific anti-human T-cell globulin (ATCG-H) was carried out by absorption of anti-human thymocyte globulin with liver-kidney homogenate, chronic lymphocytic leukemia cells of B-cell type, and erythrocytes. Subsequent testing revealed that the serum still reacted with human T-cells but no longer reduced the number of colony-forming units in culture (CFU-C). All three bone marrow recipients were treated by chemotherapeutic conditioning and total body irradiation followed by grafting of in vitro treated bone marrow from HLA-identical siblings. The transplantation of the bone marrow was well tolerated and no major side effects were encountered. No patient so far (24, 7, 6 months) has shown any signs of GvHD. The in vitro pretransplantation treatment of bone marrow with anti T-globulin may be a new approach to the prevention for GvHD in man.

Adolescent↗

[Radiation therapy of the renal tumor in children (author's transl)].

Close cooperation of pediatric surgeons and pediatric oncologists with radiotherapists, using coordinated treatment schedules conformable to the stage of the disease, and combining tumor nephrectomy, postoperative irradiation and the treatment with AMD and Vincristine, has increased the 3-year survival rate from 27% (13 of 49) up to 67% (14 of 21) for children with Wilm's tumor.

Child↗

Osteosarcoma: histological evaluation and grading.

With 60 cases of osteosarcomas a histological evaluation from + to +++ carried out for mitoses, osteoid formation, presence of multinucleated giant cells, and tumor necrosis. A subclassification in osteoblastic, chondroblastic, and fibroblastic type of osteosarcoma (according to Dahlin) and a histological grading from + to +++ based on degree of cellular atypism was also done. In our material no relations between these three types of osteosarcoma and chance for survival became evident. There was, however, a significant correlation between grade of atypism and rate of mitoses. Grading of oestosarcomas from + to +++ showed that cases with grade III osteosarcoma remained only seldomly without metastases during the course of the disease. Grade I osteosarcomas and also grade II tumors showed a higher number of patients with 2-year survival. However, neither correlation between tumor grade and incidence of metastases, nor with chances for survival were statistically significant. Nevertheless, characterization of osteosarcomas, by a histological grading from + to +++ based on cellular atypism and mitotic count is advisable, in addition to the TNM stages. This histological grading appeared to be more practicable than subclassifications of osteosarcoma by type which had been tested by us in a previous study (Konrad et al., in press).

Humans↗

[Neuroblastoma in children. Clinical staging and management (author's transl)].

Sixty-four children with neuroblastoma stage I to III c are presented. The coordinated management utilizing surgical excision, irradiation (2--5.000 rad) in stage II and III and multiagent chemotherapy is described. Favorable sites were abdomen (30) and thorax (22). In ten cases the primary site was unknown. The prognosis is influenced by several factors: Patients under 1 year of age without evidence of bone or bone marrow metastases have a favorable outcome (13/15). Nearly all patients with lesions of bone or generalized tumor in bone and/or bone marrow (stage III b and III c) failed to attain long term disease free survival despite combination chemotherapy and the use of radiation therapy (33/34). No relation between histological or biochemical characteristics and prognosis could be found. Biochemical determinations however are useful as an index of response to treatment. Prognosis was independent from sex. A review of the literature and on attempt to improve the therapeutic efficancy in stage III are reported.

Abdominal Neoplasms↗

[Juvenile rhabdomyosarcoma. Diagnosis and new therapeutic possibilities].

Seventeen children with rhabdomyosarcoma stage I to III diagnosed since 1973 are presented. The coordinated management utilizing surgical excision, irradiation (5000 rad) and systemic adjuvant multiagent chemotherapy is described. The favorable sites were head and neck sites and genitourinary region. The mean survival is at present 19 months. 14 children are alive and well. 13 children had no tumor recidivation, 1 child had 8 months after beginning of the therapy lung metastases which after irradiation with 2000 rad disappeared. 3 children (stage III) died 9, 14 and 20 months after diagnosis during therapy by metastases. Acute and late effects on normal tissues from radiation and chemotherapy were noted in 12 cases. A review of the literature and therapeutic alternatives in the future are indicated.

Child↗

[Neuroblastoma: paraneoplastic diseases and late complications (author's transl)].

Only 40 out of 104 patients with neuroblastoma survived moronger than 5 years, and 7 longer than 10 years. This indicates a 2 year remission period of 38.4%. Of the 40 surviving children, only 11 (10,4%) showed no further complications, while 29 (72,5%) children suffered from severe later complications originating from the tumor or the therapy. The skeletal system was affected in 42.9%, the peripheral nervous system in 21.5%, and the central nervous system in 19.6%. In 4 patients, we observed a statomotoric retardation and intelligence deficiency, and in 3 other children, an Australian antigenemia. The possible reason of these later complications are discussed in the paper. The high number of such complications in patients with neuroblastoma raises the question whether or not a less radical therapeutic procedure would be more advisable for differentiated tumors.

Age Factors↗

[Minimal residual disease analysis in acute lymphoblastic leukemia of childhood within the framework of COALL Study: results of an induction therapy without asparaginase].

UNLABELLED: The detection of minimal residual disease (MRD) is a major prognostic factor for treatment in acute lymphoblastic leukemia (ALL) of childhood. Several groups showed the predictive value of MRD after 5 weeks of chemotherapy (at the end of induction therapy). Patients with more than 1 leukemic cells in 100 cells (> or = 10(-2)) at this time-point have a significantly higher relapse rate. The MRD measurement has been shown to be an independent prognostic factor at several time points in the BFM study (ALL-BFM 90) as well as in the EORTC study. The aim of our investigations was the detection of MRD at the end of induction therapy within the COALL studies which is different from the above studies. In the COALL studies, therapy starts with a 1 week DNR prephase (24 h infusion on day one) and i.th. MTX. Induction therapy consisted of 3 drugs over a period of 4 weeks (Prednisolone, Vincristine and Daunorubicin), asparaginase is given later in consolidation. At the end of induction therapy, bone marrow was obtained for cytomorphologic and molecular analysis. PATIENTS AND METHODS: We investigated bone marrow samples from 76 patients. All patients were in morphologic remission at the end. of induction therapy. For MRD analysis, DNA was isolated from bone marrow mononuclear cells. Clonal T-cell-receptor (TCR) or immunoglobulin gene (IgH) rearrangements were identified by PCR. Monoclonal products were either sequenced directly (TCR) or after excision from high resolution agarose gels. Subsequently patient-specific oligonucleotides for allele-specific PCR were generated. PCR analysis was performed with 1 microgram DNA for each reaction within a semiquantitative matter. This method reached sensitivities down to 10(-5). RESULTS: Eighty-four percent of the analysed samples were MRD positive at the end of induction therapy. 20 out of 76 patient samples (26%) were highly positive (> or = 10(-2)), 28 patients had levels of about 10(-3) (37%), 16 had levels around 10(-4) (21%) and 12 patients had no detectable residual cells (16%). All analysed 15 T-ALL patients had detectable residual disease at this timepoint. Until now, 5/20 patients with very high MRD level at the end of induction therapy suffered a relapse. DISCUSSION: Patients with very high MRD level at the end of induction therapy showed an elevated risk of relapse, but the predictive value is much poorer than for example in the BFM 90 MRD-study. We suggest, that a high MRD level at this timepoint results from a different induction therapy compared to the BFM 90 study. In the COALL studies asparaginase is given only after induction therapy to decrease the risk of thrombosis. We would like to conclude that this differences were compensated later during therapy as the event free survival of both studies is similar. In conclusion, an optimal information from MRD studies is strongly associated with the given therapy. Therefore we initiated an additional MRD time-point after the first chemotherapy block in consolidation.

Antineoplastic Combined Chemotherapy Protocols↗

[The Munich study on the treatment of acute lymphoblastic leukemia in childhood (ALL 77-02)].

149 children with acute lymphocytic leukemia (ALL) were admitted to a prospective therapeutic regime. Remission induction was achieved by vincristine, daunorubicine, L-asparaginase and prednisone. During consolidation the patients received three intermediate dose methotrexate (MTX) infusions over 24 hours combined with intrathecal MTX, followed by L-asparaginase. High-risk patients were treated in addition with high dose cyclophosphamide and ARA-C over 3 weeks. Standard risk patients received cranial irradiation with 18 Gy, high-risk patients with 24 Gy. Maintenance therapy was performed with 6-mercaptopurine and MTX orally. Immunologic phaenotyping revealed: c-ALL 73%, pre-T or T-ALL 15%, c/T-ALL 4% and undifferentiated leukemia (AUL) 8%. Only 1 patient was nonresponder, 7 patients died during induction therapy, 5 patients during continuous complete remission (CCR). 18 relapses occurred, 12 of which were systemic, 8 CNS and 2 testicular relapses. In the total group the 54 months probability of CCR is 0,68 +/- 0,05 (life-table-analysis), for the reduced group 0,75 +/- 0,05. In the reduced group the probability of CCR at 54 months for standard risk patients is 0,86 +/- 0,06; for high-risk patients 0,60 +/- 0,09; for patients with c-ALL 0,73 +/- 0,08; for patients with c/T-ALL 1,0 +/- 0,0; for patients with pre-T or T-ALL 0,58 +/- 0,2 and for patients with AUL 0,45 +/- 0,25. For the reduced group the CCR probability at 54 months in relation to the leukocytes (WBC) at diagnosis is in patients with WBC less than 25 X 10(3)/mm3: 0,80 +/- 0,06; for patients with WBC greater than 25 X 10(3)/mm3: 0,63 +/- 0,11.

Antineoplastic Combined Chemotherapy Protocols↗

[Malignant testicular tumors in children and adolescents: concept of the MAHO 82 cooperative therapeutic study of the Society for Pediatric Oncology].

The German Society of Pediatric Oncology (GPO) designed a cooperative study to improve the outlook of patients with malignant (testicular) germ cell tumors. According to stage and histology of the tumor different surgical approaches to retroperitoneal lymphadenectomy are suggested. Local radiotherapy is not recommended. Adjuvant chemotherapy with Vinblastine, Bleomycin and Cis-Platinum according to stage of disease, histologic classification and age of the patient is outlined. For non-responders or patients with only partial response an alternative aggressive chemotherapy with VP 16, Ifosfamide and Cis-Platinum is guidelined.

Adolescent↗

[Treatment strategy in non-testicular malignant germ cell tumors in children and adolescents--concept of the MAKEI 83 cooperative therapeutic study of the Society for Pediatric Oncology].

In December 1982 the German Society of Pediatric Oncology (GPO) has initiated a cooperative study for non-testicular malignant germ cell tumors with initial vinblastine, bleomycin and cisplatinum chemotherapy depending on stage and histological grading, followed by ifosfamide, cisplatinum and VP 16 chemotherapy. Dysgerminoma patients with advanced disease are also treated with primary chemotherapy including vinblastine, bleomycin and cisplatinum; radiotherapy is limited to current disease. Patients with more differentiated teratomas receive combination chemotherapy with vinblastine, actinomycin D and cyclophosphamide.

Adolescent↗