Acute ascending motoric paraplegia following intrathecal chemotherapy for treatment of acute lymphoblastic leukemia in children: case reports and review of the literature.

Severe side effects of chemotherapy in pediatric patients with acute lymphoblastic leukemia are rare, but well-known. We present two pediatric patients who developed ascending motoric paraplegia (AMP) following intrathecal chemotherapy. Both patients suffered from progressive weakness of their lower extremities, neurogenic bladder dysfunction, autonomous neural dysregulation and minor sensory deficits. Despite an initially similar clinical picture, progression and outcome were fairly different. There is convincing evidence that AMP is caused by spinal cord toxicity of intrathecally applied toxic agents such as cytarabin and/or methotrexate leading to spinal demyelinisation as demonstrated by elevated myelin basic protein in cerebrospinal fluid.

Primary mediastinal large B-cell lymphoma with sclerosis in pediatric and adolescent patients: treatment and results from three therapeutic studies of the Berlin-Frankfurt-Münster Group.

PURPOSE: Primary mediastinal large B-cell lymphoma with sclerosis (PMLBL) is a rare entity of non-Hodgkin's lymphoma (NHL) arising from thymic mature B cells. Optimal treatment strategies remain to be established, especially in pediatric patients. PATIENTS AND METHODS: This study analyzes clinical characteristics and treatment outcome of 30 pediatric patients with PMLBL, diagnosed in multicenter therapy NHL-Berlin-Frankfurt-Münster Group (BFM) trials. Treatment was stratified by stage and serum lactate dehydrogenase (LDH) and consisted of four to six 5-day courses of chemotherapy using steroids, oxazaphosphorine alkylating agents, methotrexate, cytarabine, etoposide, and doxorubicin. Radiation was not part of the protocol. RESULTS: From April 1986 to August 1999, 1,650 patients with newly diagnosed NHL were enrolled in the NHL-BFM trials; 30 patients (1.8%) had PMLBL. Median age was 14.3 years (range, 1.4 to 16.7 years); 15 patients were male and 15 patients were female. With a median observation time of 5 years (range, 1 to 12 years), probability of event-free survival (pEFS) at 5 years was 0.70 (SE, 0.08). Two patients erroneously diagnosed as T-cell NHL received non-B-cell therapy and died from progress of disease. Events in 28 patients receiving B-cell therapy included early progress during therapy (n = 1) and relapse (n = 6). Residual mediastinal masses were present in 23 patients after two courses of therapy and in 15 patients after the end of therapy. LDH > or = 500 U/L was associated with increased risk of failure in multivariate analysis. CONCLUSION: PMLBL mainly is found in adolescents. Dose-intense chemotherapy including high-dose methotrexate yields a pEFS at 5 years of 0.70 (SE, 0.08). LDH is of prognostic value in pediatric patients with PMLBL.

[Improved results in the treatment of acute myeloid leukemia - Results of study AML-BFM-93 in East Germany with comparisons to the preceding studies AML-I-82 and AML-II-87]. / Verbesserte Ergebnisse in der Therapie der akuten myeloischen Leukämie - Ergebnisse der Therapiestudie AML-BFM-93 in den neuen Bundesländern im Vergleich mit den Vorgängerstudien AML-I/82 und AML-II/87 der DDR.

BACKGROUND: Three multicenter studies were conducted in East Germany on the treatment of acute myeloid leukaemia in children. The latest of the three studies (AML-BFM-93-OST) was part of the common German study AML-BFM-93. PATIENTS AND METHODS: The total number of registered patients was 262. The number and dosage of administered chemotherapeutic agents was elevated with each new study. RESULTS: Both the remission rate (85 %) and the likelihood of an event free survival (52 % after 5 years) could be improved significantly in study AML-BFM-93-OST. The results of the common German study AML-BFM-93 were identical to those of the East German part AML-BFM-93-OST. Compared with international studies it was one of the most successful treatment strategies in children with AML. Patients who showed toxic side effects to heart, liver, kidneys, skin or nervous system during the chemotherapy had a significantly lower risk of relapse, once they overcame the intensive therapy. During the five years of study AML-BFM-93-OST, treatment results could be improved despite an unchanged therapy strategy. This may partly be due to the modernisations and restorations that were carried out in many East German hospitals in this time. CONCLUSIONS: The therapy regimen of study AML-BFM-93 allowed a substantial improvement in the treatment of children with AML. Further intensification of chemotherapy should only be undertaken in accordance to the individual sensitivity of each patient.

Thrombolytic therapy in children--clinical experiences with recombinant tissue-plasminogen activator.

For the improvement of thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA) in children, more clinical data are needed. We retrospectively analyzed the clinical course of 20 patients (age ranging from 1 day to 16 years) with venous thrombosis (n = 16), arterial thrombosis (n = 2), and purpura fulminans by meningococcosis (n = 2). The venous thromboses were localized in the iliac-femoral veins (n = 9), brachiocephalic-jugular-subclavian veins (n = 6), and the superior caval vein (n = 1). The arterial occlusions were localized in the abdominal aorta and in the left pulmonary artery. Central venous catheters were of pathogenetic importance in seven cases. The patients were treated with rt-PA for 3 hours to 13 days. The dose ranged between 0.2 and 0.5 mg/kg for the initial bolus and 1.0 to 2.0 mg/kg/d for the continuous infusion. Nineteen patients received simultaneously low-dose unfractionated heparin. Complete clot lysis was detected in 11 cases, a partial lysis in 1, and in 8 patients thrombolytic therapy was not successful. An episode of hematemesis in one patient represented the only serious side effect observed in our study. A systemic decrease in fibrinogen concentration was also rare. In conclusion, thrombolysis with rt-PA represents an effective and safe therapy for children at the dosage used.

Clinical importance of prothrombotic risk factors in pediatric patients with malignancy--impact of central venous lines.

UNLABELLED: To evaluate the role of inherited thrombophilia in the development of central venous line (CVL)-related thrombosis, the following parameters were determined in 77 pediatric-oncologic patients with CVL: activated protein C (APC)-ratio, factor V (FV) G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin, coagulation factor XII, lipoprotein (a) and homocysteine. An inherited prothrombotic risk factor was found in 17 patients (23%). Four out of 14 patients with a single detect (hyperlipoproteinemia, heterozygous FV G1691A and prothrombin G20210A mutation, protein C deficiency type I) and all three patients with combined defects (heterozygous FV G1691A mutation combined with heterozygous prothrombin G20210A variant, protein S deficiency or hyperlipoproteinemia) suffered from CVL-related thrombosis. In 11 out of 77 patients (14%) a CVL-related thrombosis was detected. In 2 children thrombosis occurred a few days after asparaginase therapy and in another three thrombosis was associated with CVL-related septicemia caused by Staphylococcus epidermidis. After removal of CVL, thrombosis was detected in 5 children, in 2 without clinical symptoms but in the presence of inherited prothrombotic risk factors. CONCLUSION: The present study demonstrates the clinical importance of CVL in combination with inherited thrombophilia in the development of thrombosis in pediatric-oncologic patients. Before or shortly after insertion of CVL, patients should be tested for the presence of factor V G1691A mutation, prothrombin G20210A variant and increased lipoprotein (a) values.

Non-Hodgkin lymphoma (NHL) as a second neoplasm occurring after neuroblastoma treatment.

As far as we know, this is the first report of a non-Hodgkin lymphoma developing after successful treatment of neuroblastoma. A boy was found to have a mediastinal T-cell lymphoma at the age of 5. He had been treated for a neuroblastoma of the left adrenal region 4 years before, when by intensive chemotherapy and radiation a complete remission of the primary tumor was achieved. The second malignancy has also been controlled without evidence of recurrence 1 year after termination of treatment. We conclude that treatment of a neuroblastoma by cytostatic drugs and radiation may lead to a non-Hodgkin lymphoma as a second malignancy.

[Carl Christian Wilhelm Juch (1772-1821). His biography and his scientific work]. / Carl Christian Wilhelm Juch (1772-1821). Ein Beitrag zu seiner Biographie und seinem wissenschaftlichen Werk.

This article introduces Carl Christian Wilhelm Juch, Pharmacist, Doctor and Chemist, who, now almost forgotten, was well known in his time for his numerous works and essays on Natural Science. Some new biographic findings are disclosed. Juch's work covers a series of writings on Natural Science, in which he put great emphasis on economic and technological themes. His translation of and commentary on the Pharmacopoea Borussica 1805 provided an important contribution to pharmacy. In 1801 Juch was appointed Professor of Medicine and Chemistry at the University of Altdorf. In his position as University Professor he went 1805 to the Munic Lyceum and in 1808 to the Augsburg Realinstitut in order to teach Chemistry, Natural History and Dietetics. In 1816/17 he retired due to poor health. Juch died in Augsburg in 1821 at the age of forty-eight.

[Detection of Exophiala dermatitidis (Kano) De Hoog 1977 in septicemia of a child with acute lymphatic leukemia and in patients with cystic fibrosis]. / Nachweis von Exophiala dermatitidis (Kano) De Hoog 1977 bei Septikämie eines Kindes mit akuter lymphatischer Leukämie und bei Patienten mit Mukoviszidose.

In 1992 black yeasts of the species Exophiala dermatitidis were isolated for the first time from patients at the University Clinics in Dresden. Since that time this relatively rarely detected fungus has been frequently cultivated from clinical specimens. Our observations were: Patient with acute lymphatic leukaemia: In a 3 1/2 years old boy E. dermatitidis was isolated from 8 blood cultures during a septicaemic phase. Elimination of the fungus and decreasing of the fever were reached after removing a central venous catheter and treatment with amphotericin B and 5-fluorocytosine for 3 weeks. In this patient E. dermatitidis was assessed to be the cause of the septicaemia setting in via catheter. Patients with cystic fibrosis: In 8 of 51 mycologically surveyed patients E. dermatitidis was frequently - in 2 cases for a long time up to 7 months - isolated from sputum specimens. The occurrence of this fungus was considered to be a colonization with subclinical development. In these patients no fungal invasion or systemic mycosis were seen. The administration of itraconazole for 4 respectively 7 months did not succeed in eliminating E. dermatitidis out of the respiratory tract. It is recommended to include mycological longtime cultures in the surveillance of cystic fibrosis patients for detection of E. dermatitidis.

[Encephalopathy in leukemia treatment in children]. / Enzephalopathie während der Leukämiebehandlung bei Kindern.

Side effects on the central nervous system by antileukemic treatment have been well known for a long time. We report on 2 patients suffering from a severe encephalopathy during antileukemic therapy. Furthermore the results of cerebral computer tomography in 50 children with acute leukemia have been analysed. In 21 patients morphological findings were evident. Four patients had CCT-changes already before the beginning of their treatment. Initially in 2 patients leukemic cerebral infiltrations were detected. The importance of the computer tomography for the detection of cerebral affections by disease and treatment is demonstrated.

[Thrombocytopenia after autologous bone marrow transplantation in in acute lymphatic leukemia]. / Thrombozytopenie nach autologer Knochenmarktransplantation bei akuter lymphatischer Leukämie.

There is reported about the treatment of refractory thrombocytopenia in a 9 years old boy following the autologous bone marrow transplantation for acute lymphoblastic leukaemia. The megakaryocytes were found diminished in the bone marrow smears. Controls of the thrombocyte count and the kinetics with radioactively labeled platelets of a donor spoke in favour of immunothrombocytopenia. Threatening bleeding complications challenged the use of all treatment possibilities. The irradiation of the spleen was without any success. After the splenectomy the thrombocyte count increased slowly, but after a remarkable lag phase, however. A diminished reproduction capacity of the bone marrow graft for special cell sorts has to be taken into account in such cases. The usual cytodynamics after splenectomy cannot be expected at all.