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Das papillare Nierenzellkarzinom beim Kind ist eine seltene Erkrankung und sollte als eigenstandige Entitat betrachtet werden, da sie sich hinsichtlich Symptomatik, Verlauf und Prognose vom Erwachsenentyp unterscheidet. Es wird die klinische und diagnostische Problematik bei Diagnosestellung, Prognose und Therapie dieser im jugendlichen Alter sehr seltenen Erkrankung anhand der Literatur diskutiert.

In hospitals, nursing homes and home-care facilities the emergence and dissemination of antibiotic-resistant bacteria is causing increasing problems in wound care. Methicillinresistant Staphylococcus aureus (MRSA) is one of the most prevalent and recalcitrant pathogens compromising wound healing. Aside from the microenvironmental problem, it is having a big impact on health-care costs.

The purpose of this study was to examine the outcome of attempted radical surgical resection in patients with stage IV neuroblastoma. Between 1989 and 2003, 20 (median age 2.4 years, range 0.5-8.7 years) children with stage IV neuroblastoma were treated at the Department of Pediatrics. Surgery was performed in 7 consecutive children (6 male and 1 female) between July 1997 and February 2002 at the Department of Urology in Bonn. Mean age at diagnosis was 57 months (21-104 months). Mean age at the time of surgery was 54 months (8-390 months). Follow-up was available for all patients (100%) and mean follow-up after the operation was 32.5 months (4-56 months). Primary localization of the tumor was retroperitoneal in all cases; 4 out of 7 patients (57%) also had additional adrenal, 3 out of 7 (42%) paraganglion and 1 out of 7 (14%) thoracic primaries. Bone marrow and lymph node metastases were found in all patients (100%). Surgery led to complete tumor resection in 6 out of 7 patients (85%). Surgical approach was abdominal (chevron incision) in 6 out of 7 (85%) of the patients, in one patient the approach was thoraco-abdominal. After induction chemotherapy and delayed surgery, 6 out of 7 (86%) patients showed a complete remission (CR) and the mean CR lasted for about 27.7 months (range 3.1-55.4 months). At the last time of follow-up 5 out of 7 (71%) patients were alive, 2 had died due to recurrent disease. Mean time to recurrent disease was 24 and 51 months, respectively. Mean overall survival time since diagnosis was 38.3 months (11-64 months) and mean event-free survival was 34.5 months (11-60.3 months). The final outcome, overall survival and event-free survival time was influenced by metastatic or local relapse. Tumor resection is beneficial but the value of surgery can only be judged when we are able to control metastatic disease in stage IV neuroblastoma. The final outcome may rely on the extent of complete surgical resection, but is also related to treatment of metastases. A longer follow-up period is indicated to detect long term outcome.

Background Tumor-free survival from hepatoblastoma could be improved to 75 % of all patients by combining surgery with chemotherapy. This figure reaches 90 % for potentially resectable (SR, standard risk) tumors. The outcome of high risk (HR) hepatoblastomas with multifocally disseminating growth in the liver, invasion of large vessels, extrahepatic extension and metastases is still poor, especially since these tumors often rapidly develop resistance against cytotoxic drugs. In the Study HB 99 of the German Society for Pediatric Oncology and Hematology, it is attempted to reach an improved regression and thereby a better prognosis with inauguration of high dose (HD) chemotherapy. This first interim analysis shall evaluate the preliminary results of this strategy. Patients and methods 53 children with a hepatoblastoma have entered the study. 8 patients were excluded from this analysis because of different or not completed therapy. 10 SR-patients with a small tumor underwent a primary complete (stage I, n = 8) or microscopically incomplete (stage II, n = 2) resection. These received two courses of ifosfamide (3 g/m2), cisplatin (100 mg/m2), and doxorubicin (adriamycin, 60 mg/m2) (IPA). 26 patients with an extended, but potentially resectable tumor (stage III SR) were preoperatively treated with three courses of IPA, followed by a tumor resection and a 4th course of IPA. 9 patients with a HR-hepatoblastoma (3 x stage III HR, 6 x stage IV) were treated with two courses of carboplatin (800 mg/m2) and etoposide (400 mg/m2) (CARBO/VP16). In case of tumor response, they received one or two courses of HD-chemotherapy with carboplatin (2000 mg/m2) and etoposide (2000 mg/m2) after sampling of peripheral stem cells, followed by resection of the primary tumor and metastases, whenever possible. IPA therapy was administered in case of inadequate response to these drugs. The preliminary therapy results were analyzed in relation to the post-surgical stages (I-IV) and to the SIOPEL-PRETEXT (Pretreatment extend of disease) -grouping system (groups I-IV, V, P, E, M). Furthermore, the response of HR-hepatoblastoma to CARBO/VP16, the achieved resectability, and the acute toxicity were evaluated. Results 40 of 45 (89%) of all hepatoblastoma patients are in remission. 34/36 (94%) SR-patients (stage I - III-SR) are tumor-free, two died of therapy complications. 6 HR-patients are tumor-free, one alive with tumor and two died. In relation to the PRETEXT-grouping, a remission was achieved in 4/4 group I, 14/16 group II, 16/16 group III, 5/6 groups I-III, V, P, E, M, and 1/3 group IV tumors. 6/9 HR-hepatoblastomas were good responders to CARBO/VP16, 5 of these are in remission. 3/9 tumors did not respond, only one could be eradicated by a liver transplantation. In 5/9 HR-patients a R0-resection was possible after chemotherapy, in one a R1-resection, one received a liver transplant, and two tumors remained inoperable. In 4/6 cases lung metastases could be completely removed or, in one case, they had vanished in the CT-scan under chemotherapy. These 4 patients remained in remission. The most frequent severe toxicity of CARBO/VP16 concerned leucopenia (23% of courses) and thrombocytopenia (85% of courses). Under HD therapy severe infections (2/7, 28%) and elevation of transaminases occurred. There was no toxic death. Conclusions A cure rate of over 90% can be reached by conventional cisplatin and doxorubicin containing chemotherapy and radical surgery in SR-hepatoblastoma. 50-60% of all hepatoblastomas respond to CARBO/VP16. In these cases HD-therapy with these drugs is highly efficient and enables a remission in the majority of advanced and metastasised HR-hepatoblastoma. A larger number of patients and longer follow-up have to confirm these results. Therefore, the study will be continued.

PURPOSE Prenatal plasma concentrations of erythropoietin in fetuses with Rh disease should contribute information to the clinical course and therapeutic control of this disease. METHOD Fetal plasma erythropoietin (Epo) and haemoglobin (Hb) concentrations were measured in 145 umbilical venous blood samples of 30 fetuses with Rh disease at 20 to 38 weeks' gestation. RESULTS Both Epo and Hb concentrations were independent of the gestational age in red blood cell-isoimmunised pregnancies. The Hb concentration correlated significantly with Epo concentration without intrauterine transfusion (IUT) (r = -0.519, p = 0.005) and after IUT (i = -0.212, p = 0.01). A haemoglobin deficit of 3 g/dl at 20 weeks' gestation increased to 6 g/dl at 38 weeks' gestation in spite of IUT (p = -0.354, p < 0.001). CONCLUSION Even with IUT, Epo concentrations increase with gestational age during these pregnancies. This is due to increasing Hb deficits indicating fetal hypoxia which might be prevented by increasing volumes of transfusion.

More than half of the children and adolescents with malignant brain tumors will relapse following initial therapy. Irrespective of the therapeutic modalities the prognosis of patients with recurrent or metastatic brain tumors is still poor. New strategies such as high dose chemotherapy (HDCT) with autologous blood stem cell transplantation (ABSCT) offer the possibility to improve the longterm prognosis of these patients. Following conventional chemotherapy with carboplatin/etoposide and after achieving complete or partial remission (CR or PR) 10 patients aged from 3.2 to 25.5 years (median, 10.3 years) with refractory or recurrent malignant brain tumors (anaplastic astrocytoma/glioblastoma, n = 2; medulloblastoma/PNET, n = 6; ependymoma, n = 1; plexus carcinoma, n = 1) received in a pilot study one course of HDCT with ABSCT. The consolidation regimen consisted of thiotepa (400-600mg/m2/d, i.v. 6 h, d-9), carboplatin and etoposide (500mg/m2/d, CVI 24h, d-8 to d-5, respectively) and was followed by the retransfusion of autologous blood stem cells on day 0. Before starting HDCT 6 patients showed CR and 4 patients had PR or stable disease (SD). Following the HDCT 3 of the 4 patients with residual tumor had CR or PR. 6 patients have remained in continuous CR or SD 8 to 41 months (median 17.2 months) after the HDCT. 2 patients relapsed 8.5 and 9.5 months after HDCT and died from progressive disease. Two patients died therapy-related from systemic aspergillosis and were not evaluable for response. Hematological recovery with an absolute neutrophile count of > 0.5 x 10(9)/l and a platelet count of > 30 x 10(9)/l was reached on days +11 (median; range, +9 to +14) and +16 (median; range, +6 to +47), respectively. The main nonhematological toxic effects were infections, severe mucositis, and hyperbilirubinemia. Although the long-term efficacy of HDCT with ABSCT is still not evaluable and the toxicity of this regimen is high, a multicenter phase II trial seems to be justified in view of the poor prognosis of recurrent or refractory brain tumors in children and adolescents.

Background The introduction of cranial radiotherapy (CRT) has provided efficient control of overt or subclinical meningeosis in acute lymphoblastic leukemia (ALL). Especially due to the long-term toxicity of CRT, reduction or elimination of radiotherapy appeared mandatory after cure rates of more than 70% had been achieved in ALL. The Berlin-Frankfurt-Munster (BFM) Study Group initiated several attempts in certain ALL subgroups to omit or reduce CRT while using more CNS-directed chemotherapy but without extended intrathecal treatment during maintenance therapy. This analysis summarizes the essential results that are in particular relevant because irradiation of the central nervous system (CNS) has been further reduced in the most recent trial ALL-BFM 95. Patients and methods More than 4000 patients enrolled between 1981 and 1995 in one of the last four ALL-BFM trials have been analyzed to demonstrate the efficiency of intensive systemic and intrathecal chemotherapy with or without reduced CRT in the prevention of CNS relapses. Results In trial ALL-BFM81, it was shown that only in low-risk (LR) patients preventive radiotherapy can be replaced safely by intermediate dose (0.5 g/m2) methotrexate (MHD-MTX). In intermediate risk (IR) patients this attempt failed: IR pts had 8 times more CNS relapses if treated by MHD-MTX without CRT. In the subsequent trial ALL-BFM 83, all pts received MHD-MTX. IR pts were randomly treated with 12 or 18 Gy of preventive CRT which did not result in a significantly different outcome. The results from the subsequent trial ALL-BFM 86, using a more intensive consolidation with high-dose methotrexate (HD-MTX), demonstrated that the elimination of CRT in low-risk ALL, the reduced CRT of 12 Gy for IR, 18 Gy for medium (MR), and the reduced CRT with 18 Gy for high risk (HR) ALL, respectively, was justified: the incidence of relapses with CNS involvement was reduced to less than 5% (Reiter et al. 1994, Blood 84: 3122). When even less intensive preventive CRT (12 Gy for all medium and high risk patients) was used in trial ALL-BFM 90, the rate of CNS-related relapses was again below 5%. HR patients now treated with more CNS-directed chemotherapy had the lowest rate of CNS-related relapses observed so far in the BFM trials, even though CRT was also reduced to 12 Gy. Patients with T-cell ALL were shown to be protected from CNS recurrence by the combination of CRT (12 Gy) and HD-MTX more effectively than by HD-MTX in consolidation and TIT therapy during maintenance, especially if they presented with high WBC as shown in a joint AIEOP/BFM analysis (Conter et al. 1997, JCO 15: 2786). Patients with overt meningeosis which are characterized by a high leukemic cell load at diagnosis had a rate of recurrences that was comparable to that of patients with high WBC but no CNS disease. Conclusion Low-risk ALL patients can be efficiently prevented from CNS relapse by intensive systemic and intrathecal chemotherapy without CRT. Patients with intermediate or medium risk ALL, including T-cell ALL, did not suffer from more CNS or systemic relapses when CRT was reduced to only 12 Gy. Patients with inadequate response to therapy are at particularly high risk for relapse with CNS involvement. Therefore, more CNS-directed systemic and intrathecal chemotherapy was applied in trial ALL-BFM 90, combined with only 12 Gy cranial irradiation, and improved the control of CNS recurrence. It seems likely that larger subsets of B-precursor ALL can be protected from CNS-related relapse by intensive chemotherapy without extended IT treatment and without CRT. This is being investigated in the ongoing trial ALL-BFM 95.

β-Laktam-Antibiotikum allein oder in Kombination mit einem Glykopeptidantibiotikum oder einem Aminoglycosidantibiotikum konnte bei erwachsenen Patienten eine hohe Wirksamkeit in der Behandlung der febrilen Neutropenie belegt werden [8, 10, 18]. Umfangreiche klinische Studien zur Wirksamkeit gleichartiger Therapieschemata in der padiatrischen Onkologie sind selten. In einer Multizenterstudie wurde gepruft, ob eine Kombinationstherapie mit Ceftazidim und Teicoplanin als Initialtherapie einer antibiotischen Sequentialtherapie bei Kindern und Jugendlichen mit febriler Neutropenie effektiv ist.

The Cooperative German Paediatric Liver Tumour Study HB89 was conceived to evaluate the efficiency and toxicity of ifosfamide, cisplatin and doxorubicin (IPA) in children with resectable and non-resectable hepatoblastoma (HB) and to determine late sequelae including tubular nephropathy of tumour treatment. The study also assessed the results of a surgical strategy, which adapts the procedure at the initial operation to the tumour's extension in the liver. The relationship of the tumours' histological differentiation to response to chemotherapy was also examined. Patients with a HB restricted to one liver lobe underwent primary resection. Larger tumours were initially treated with IPA chemotherapy and resected at second-look surgery. All patients received IPA adjuvantly after tumour resection. The IPA regimen consisted of ifosfamide 3.5 g/m2 (over 72 h days 1-3), cisplatin 100 mg/m2 (over 5 days 4-8) and doxorubicin 60 mg/m2 (over 48 h, days 9-10). Median follow-up of survivors was 64 months (range 28-82). Long-term disease-free survival (DFS) was for stage I: 21/21; stage II: 3/6; stage III: 28/38; and stage IV: 2/7 (overall 75%). Severe surgical complications occurred in 15% (4/27) of primary and 21% (8/38) of secondary resections with no lethality. 44/45 stage III/IV HB displayed PR after two IPA courses. Drug resistance developed in 8/12 tumours after four or five chemotherapy courses. Acute toxicity was observed in 34/242 (14%) IPA courses. Late sequelae were found in 7/54 (13%) of survivors, and subclinical renal tubulopathy occurred in 7/41 investigated patients (17%). Despite a more favourable prognosis in pure fetal and predominantly fetal histology, statistical analysis revealed no relationship between tumour differentiation and response to chemotherapy. In conclusion, IPA chemotherapy in combination with delayed surgery was highly effective in the treatment of HB.

94 children with a primary liver neoplasm were registered in the Cooperative Pediatric Liver Tumor Study HB-89 of the GPOH from 1988 to 1992. 64 of these had a hepatoblastoma (HB), 12 a hepatocellular carcinoma (HCC), 2 a sarcoma and 16 a benign tumor. 51 (80%) patients with an HB were 6 to 36 months of age, 9 with an HCC above 10 years. Initial serum-alpha-fetoprotein (AFP) was elevated in 51 HB patients and exceeded the 3-fold of normal range in 45. Children with low ( 1,000,000 ng/ml) levels had a significantly worse prognosis than those with intermediate values (p = 0.0014). AFP was moderately elevated in 9 HCC patients. All other tumor markers were only irregularly above normal range. 48 (77%) of HB patients survived, 45 (73%) are tumor free. All of 18 stage I and 4/5 stage II patients are in remission. After chemotherapy 30/36 stage III HBs and 2/5 stage IV HBs could be resected, 9 of these patients suffered from tumor relapse. Disease-free survival was 100% for stage I, 80% for stage II, 68% for stage III and zero for stage IV HB (p = 0.0005). Surgical complications occurred after 8% of biopsies, 13% of limited primary resections and 25% of extended secondary resections. There was no perioperative death. The completeness of tumor resection at primary or delayed surgery correlated significantly with patients disease-free survival (p < 0.0001). Chemotherapy with ifosfamide, cisplatin and adriamycin was effective in HB. 203 courses were given in 61 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

During or immediately following L-asparaginase (L-asp) therapy especially intracranial thromboembolic or hemorrhagic complications due to hemostatic imbalance have been observed. We report about 6 children who had intracranial thrombosis or hemorrhage after 3 to 8 doses of L-asp. Initial symptoms of the cerebral events were similar--seizure, coma, hemiparesis and disorientation. All patients were examined by cerebral computerized tomography (CT) or/and magnetic resonance imaging (MRI). Three patients had a dural sinus thrombosis, one had an intracranial hemorrhage and two a hemorrhagic infarction with typical findings in the cerebral CT or MRI. Two other patients were interpreted as having peripheral thrombosis. They showed nontypical hypodense cortical and subcortical areas without any contrast medium enhancement in CT and hyperintense areas in T2-weighted MRI scan. All patients recovered from neurological symptoms, and showed obvious regression of CT and MRI findings which correlate with the good prognosis of these complications. Both CT and MRI are useful in diagnosis and follow-up of cerebrovascular complications of L-asp therapy. The CT and MRI findings of the reported cases seem to reflect different appearances of the same entity, i.e. thrombosis of venous vessels of different size with or without congestive edema and hemorrhagic complication.

We report a 3 year-old boy in Tanzania with an abdominal mass and isosexual precocity due to an hCG-secreting hepatoblastoma. Due to the limited availability of local diagnostic testing, surgery and chemotherapy were completed before immunohistochemical and endocrine results were available.

Background Hepatoblastoma (HB) is the most common liver tumor of childhood, and comprises approximately 1% of all pediatric malignancies. Although recent data from multicenter trials of GPOH, SIOP, CCG and POG indicate a remarkable improvement of therapy results, the prognosis of advanced or recurrent HB is still not satisfying. Patients and methods During 1989 and 1997, the German Cooperative Pediatric Liver Tumor Studies HB 89 and HB 94 registered 141 patients with HB, who were treated according to the study protocols. These patients received standard chemotherapy with ifosfamide, cisplatin and doxorubicin (IPA) pre-operatively and/or post-operatively. Fourteen children with recurrent or advanced HB were additionally treated with carboplatin and etoposide (CARBO/VP 16), the reason being observations of drug resistance in children with HB after four or more courses of IPA-therapy in the HB 89 study. The clinical data and course of these patients were evaluated to investigate the efficiency of CARBO/VP 16 chemotherapy and for analyzing the role of surgery. Results Mean follow-up for survivors was 4.3 years (range 13 months-8 years). Tumor resection was attempted in 13 children but, in only 3 cases, was a complete tumor resection achieved in one operation. There was no perioperative death, and 7 of the patients (50%) are in remission. Two patients underwent adjuvant chemotherapy with CARBO/VP 16 for advanced HB at first operation: all are alive and well. Five patients with local relapse and/or distant metastases responded partially to CARBO/VP 16 therapy, and a complete remission was achieved in one patient. In five patients, progressive disease was observed during therapy with CARBO/VP 16. One patient, stable while on chemotherapy, had a successful resection. Acute toxicity of chemotherapy was observed in 7 patients (50%). Conclusion An aggressive approach using IPA and CARBO/VP 16 chemotherapy and highly developed surgical techniques may improve the prognosis of advanced or recurrent HBs.

Clinical data and tumor histology of 37 patients with advanced and/or metastatic hepatoblastoma (32 stage III and 5 stage IV) treated according to the protocol of the German Cooperative Pediatric Liver Tumor Study HB-89 from 1988 to 1992 were studied for prognostic factors. Twenty-three patients (73%) were free of tumor 9 months to 5 years (median, 36 months) after treatment, whereas 4 experienced progressive disease, 7 had local relapse, and 3 had recurrent metastases. None of 2 patients with primary lymph node involvement or 5 with primary metastases remained disease-free. Chemotherapy with ifosfamide, cisplatin, and adriamycin was effective in reduction of tumor to resectability in 33 (89%) patients. Drug resistance developed in 6 of 11 patients treated with four or more courses of chemotherapy as could be shown by monitoring of serum-alpha-fetoprotein (AFP) and serial investigations of tumor expansion with sonography and computed tomographic (CT) scan. Only 1 of these patients survived after a liver transplantation. Completeness of tumor resection at second- or third-look laparotomy was significantly related to disease-free survival (P.0001). Patients with initial serum-AFP values100 ng/mL or1,000,000 ng/mL had a worse outcome than those with immediate levels (P = .044). The rate of decrease of serum-AFP during chemotherapy was significantly related to prognosis (P = .003). Growth pattern of tumor within the liver (ie, defined nodes versus diffusely disseminated) (P = .011) and vascular tumor invasion (P = .026) were valuable prognostic factors, whereas tumor volume, local infiltration of surrounding tissue, histological subtypes, and epithelial differentiation were not significantly related to the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunsupprimierte Patientinnen nach Nierentransplantationen erkranken 10–20 x haufiger an Ca. colli und seinen Vorstufen als die Normalbevolkerung (Halpert 1986). Die Grunde hierfur sind unbekannt.

Anthracyclines are among the most useful drugs in the treatment of both lymphoblastic (ALL) and nonlymphoblastic (ANLL) acute leukemias of childhood. However, the benefit of the most commonly used anthracyclines daunorubicin and doxorubicin is limited by their cardiotoxicity [1] and by resistance against these compounds. The daunorubicin analog idarubicin (4-demethoxydaunorubicin) might be less cardiotoxic and has shown greater antileukemic efficacy in some preclinical and clinical trials [2]. In addition, the chemical structure of idarubicin leads to appreciable resorption of active drug after oral application [3, 4], allowing therapy in an outpatient setting. We therefore conducted an open, multicenter trial assessing the toxicity and efficacy of oral idarubicin in refractory acute leukemia in children.

The clinical pharmacokinetics of mitoxantrone in hyperthermic, isolated perfusion of the leg were studied in five patients exhibiting solitary, localized malignant melanoma. Mitoxantrone was given as four 1-min infusions at 15-min intervals into the arterial line of the perfusion system at a total dose of up to 14 mg/m2. The mean half-lives for mitoxantrone in the blood circulation of the leg were: t1/2 alpha (distribution phase), 25.5 s, and t1/2 beta (elimination phase), 14.9 min. The mean volume of distribution at steady state in the leg was 25.6 1. In the arterial part of the perfusion, the mean AUC was 155.9 mg min l-1, and that in the corresponding venous part was 91.6 mg min l-1. Leakage of the drug from the leg into the systemic circulation amounted to 1.2% of the total delivered dose; 91% of the delivered dose remained in the leg after the perfusion had been completed. The mean elimination half-life of mitoxantrone in the systemic circulation was 123 min and the corresponding AUC for systemic concentrations was 8.59 mg min l-1. The present data revealed a high uptake of mitoxantrone into the leg and low systemic drug concentrations due to minor leakage, suggesting that mitoxantrone might be a good candidate for use in isolated, hyperthermic limb perfusion.

During the past 5 years, in the German Berlin-Frankfurt-Mimster (BFM) study group a standard treatment has been established for relapse of childhood acute lymphoblastic leukemia (ALL) [1]. In study ALL-REZ BFM 85 remission rates were improved compared with the preceding study ALL-REZ BFM 83. Furthermore, by use of methotrexate (MTX) given at a dose of 1 g/m2 for 36 h there is good evidence for more effective control of bone marrow leukemia (G. Henze et al., this volume). No clear improvement was found, however, in terms of long-term event-free survival of these children, so far, because of an inappropriate high incidence of second extracompartmental relapses, especially in the CNS. The purpose of this report is to evaluate the impact of secondary CNS relapses on the prognosis of children with first isolated marrow relapse and the interrelationship between the duration of systemic disease control and the risk of subsequent extracompartmental leukemia.

Im Rahmen der AML-Rezidivstudie BFM-85 wurden 19 Kinder mit AML mit der Kombination von hochdosiertem Cytosin-Arabinosid und Mitoxantron behandelt. Alle Kinder waren initial entsprechend dem AML-BFM-83 Protokoll behandelt worden. 6 Kinder waren durch dieses Protokoll nicht in Remission gelangt; 9 Kinder hatten wahrend oder nach der Erhaltungstherapie ein Rezidiv erlitten. Bei 4 Kindern waren nach Induktions- und Konsolidierungstherapie AML-BFM-83 noch residuale Blasten im Knochenmark vorhanden (Ml/2-Mark). 6 der 15 therapierefraktaren Kinder und alle 4 Kinder mit ungenugen-dem Ansprechen auf die Induktions- und Konsolidierungstherapie AML-BFM-83 erreichten durch die Rezidivtherapie eine Vollremission. 2 Kinder verstarben in Knochenmarkaplasie, 1 Kind sprach nicht auf die Rezidivtherapie an. Ein Kind erlitt nach weiterer Therapie mit Mitoxantron eine todliche Kardiomyopathie, alle Kinder gelangten in eine im Median 27 Tage anhaltende Knochenmarkaplasie. Unsere Daten zeigen, das HD-ARA-C in Kombination mit Mitoxantron eine hohe antileukamische Aktivitat bei Kindern mit refraktarer AML besitzt.

Since the long-term disease-free survival rate in adjuvantly treated osteosarcoma has nowadays reached a level of about 70%, increasing interest is also being directed towards primarily disseminated forms of the disease. Primary metastases, which were confined to the lungs in 42 cases, were detected in 59 out of 421 patients from the prospective therapy trials COSS-80 and COSS-82. The primary tumors were more frequently localized in the proximal femur and flat bones as compared to patients without detectable metastases at diagnosis. Following chemotherapy and surgery of the primary tumor, 15/31 (48%) patients whose metastases were excised have survived for 4-8 years, in contrast to only 1/22 (5%) of those patients whose metastases could not be removed for a variety of reasons. Clinical or histological evidence of tumor response after primary chemotherapy significantly influenced the outcome of the metastasectomized patients.

11 patients with refractory acute leukemia of childhood were treated with idarubicin per os. Bone marrow toxicity which was observed at a dose level of 60 mg/m2 p.o. (3 x 20 mg q 24 hrs p.o.) per 3 weeks was found to be the dose limiting factor. In contrast to the first phase I study of Tan et al. (16) the maximal tolerated dose in the present study was found to be lower at a level of 90 mg/m2 p.o. (3 x 30 mg/m2 p.o. q 24 hrs) per 3 weeks. Therefore, we recommend a dosage of 60 mg/m2 p.o. (3 x 20 mg/m2 p.o. q 24 hrs) per 3 weeks as a starting dose for phase II/III studies. 2 out of the 11 anthracycline pretreated patients (91-880 mg/m2) with acute leukemia reached a complete remission undergoing idarubicin p.o. as a single therapy.

Children receiving cytotoxic drugs were given 7 S IgG or placebo before the period of neutropenia (less than 500/mm3 neutrophils) in a double-blind study. Though the IgG levels differed significantly, fever as the most reliable sign of infection occurred not less often than in the placebo-group. There is no indication for the routinely prophylactic administration of immunoglobulins to oncological patients. The therapeutic benefit of immunoglobulin substitution in cancer patients needs verification.

Retinal medulloepithelioma is a very rare form of neoplasm generally occurring in infancy; it is congenital in most cases [1, 15]. About 100 cases have been described so far. Some time ago, we had the opportunity of diagnosing a growth of this kind in a 10-year-old girl.

Children with leucemias or solid tumors receive intensive chemotherapy for periods of several months. Frequent infectious episodes require antimicrobial therapy for days or weeks. Surveillance cultures of pharynx, urine, vagina, rectum, and surface lesions as well as the antibiotic sensitivities were obtained three-weekly. In case of fever these specimen and multiple blood cultures were taken again. If physical examination and chest X-ray showed no signs of infection but neutropenia (500 granulocytes/mm2 or less) the patients are started on broad spectrum antibiotic coverage. The regimen was changed if bacteriological results or clinical deterioration required it. Otherwise the patients was treated until neutropenia and fever subsided for at least two days.

To elucidate the mechanism of cyclophosphamide (CTX)-induced antidiuresis, plasma and urine volume as well as serum electrolytes, creatinine, osmolality, and appropriate hormones were monitored serially during 19 courses of chemotherapy. In spite of plasma hypotonicity and urinary hypertonicity, the plasma vasopressin concentrations were unaltered. Intravenous isotonic hydration did not prevent water retention, but did not lead to plasma hypotonicity, and compensated for modest urinary sodium losses. Furosemide diuresis did not prevent the development of hyponatremia in patients receiving hypotonic hydration. The results indicate that the origin of this self-limited syndrome is a direct effect of CTX on the renal tubule, permitting increased water reabsorption and sodium loss. The likelihood that water and salt imbalance will develop after CTX administration can be reduced by vigorous isotonic hydration, and pharmacological diuresis.

In a retrospective study, 108 thoracic CT-scans of 18 patients aged 5–25 who had received cytotoxic treatment for solid tumors were evaluated. The thymic size decreased in 15/17 patients during treatment and increased in 14/15 after the end of therapy. In 5/5 patients, the change could also be detected with relapse therapy. These changes have to be considered in the evaluation of a mediastinal mass suspected of metastasis during and following cytotoxic therapy.