[Analysis of the porphyrins of erythrocytes].
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Chemistry, Clinical↗
Biomedical subjects
U Bode
Publications and source records attributed to U Bode.
Donor toxicity in granulocyte collections: association of lichen planus with the use of hydroxyethyl starch leukapheresis.
A normal male volunteer developed lichen planus in association with leukapheresis, with HES used to increase granulocyte yield. Although there is no direct proof of a causative relationship, the temporal association of the onset of initial symptoms and HES infusion strongly supports such a conclusion.
Adult↗
Boswellic acids in the palliative therapy of children with progressive or relapsed brain tumors.
19 children and adolescents with intracranial tumors received a palliative therapy with H 15 at a maximum dose of 126 mg/kg BW/day. All patients had previously been treated with conventional therapy. No side effects were observed during a median 9 months application. The recently reported antiedematous effect of H 15 was documented by MRI in one patient with a peritumoral edema, thus sparing steroid therapy with its typical side effects. Five/19 children reported an improvement of their general health status; this might be a psychological effect of hope for tumor response during palliative care. Three/17 patients with malignant tumors showed a mainly transient improvement of neurological symptoms such as pareses and ataxia. Three further patients showed an increased muscular strength and one cachectic patient achieved a weight gain. These improvements might be attributed to the antiedematous effect of H 15. Because of the palliative situation of these patients, H 15 application was performed without prior rebiopsy for histological evaluation. Overlapping effects with a previous radiotherapy or chemotherapy may have occurred. An antiproliferative effect cannot be stated. To prevent an uncritical use of H 15, further studies with prospective central documentation have to be initiated to evaluate the clinical indications for H 15 in palliative therapy, optimal dosage and duration of application.
Adolescent↗
[Differentiated treatment protocols for high- and standard-risk hepatoblastoma--an interim report of the German Liver Tumor Study HB99].
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.
Adolescent↗
Results of the SIOP 93-01/GPOH trial and study for the treatment of patients with unilateral nonmetastatic Wilms Tumor.
BACKGROUND: The treatment of Wilms Tumor is integrated into clinical trials since the 1970's. In contrast to the National Wilms Tumor Study Group (NWTSG) the SIOP trials and studies largely focus on the issue of preoperative therapy to facilitate surgery of a shrunken tumor and to treat metastasis as early as possible. PATIENTS AND METHODS: In the SIOP 93-01/GPOH trial and study 1 020 patients with a newly diagnosed renal tumor were registered. 847 of them had a histological proven Wilms Tumor, of whom 637 were unilateral localized, and 173 tumors had an other histology [40 congenital mesoblastic nephroma (CMN), 51 clear cell sarcoma (CCSK), 24 rhabdoid tumor (RTK) and 58 other tumors]. Preoperative chemotherapy in benign tumors was given to 1.3 % of the patients. The main objective of the trial was the randomized question, if the postoperative two drug chemotherapy for stage I in intermediate risk or anaplasia can be reduced from conventional 3 courses to an experimental 1 course without loss of efficacy. RESULTS: 519 patients with unilateral nonmetastatic Wilms did receive preoperative chemotherapy. The histology in this group of patients was of intermediate risk in 469 (90 %) patients, 14 (3 %) tumors were low risk and 36 (7 %) high risk. The stage distribution of the tumors was stage I in 315 (61 %), stage II N- in 126 (24 %), stage II N+ in 25 (5 %) and stage III in 36 (7 %) patients. In 17 (3 %) patients the tumor stage remained unclear. Tumor volume was measured in 487 patients before and in 402 after preoperative chemotherapy. The median tumor volume did shrink from 353 to 126 ml. The amount of volume reduction depends on the histological subtype. The event free survival (EFS) after 5 years was 91 % for all patients with unilateral Wilms tumor without distant metastasis. Randomisation was done in 43.7 % for stage I patients and there was no difference in EFS for both treatment arms (90 versus 91 %). The EFS is identical for patients with stage I and II N- (0.92), as well as for stage II N+ and III (0.82). The tumor volume after chemotherapy is a prognostic factor for intermediate risk tumors with the exception of epithelial and stromal predominant tumors. These two subtypes often present as large tumors, they do not shrink during preoperative chemotherapy but they still have an excellent prognosis. On the other hand the prognosis of patients with blastemal predominant subtype after preoperative chemotherapy is worse than in any other patient group of intermediate risk tumors. There are less blastemal predominant tumors compared to primary surgery, but they are chemotherapeutic resistant selected by the preoperative chemotherapy. CONCLUSION: Patients with unilateral Wilms tumor without metastasis have an excellent prognosis. The post-operative chemotherapy in stage I can be reduced to 4 weeks without worsening treatment outcome. The reduction of the tumor volume could be identified as a helpful marker for stratification of post-operative treatment. Post-chemotherapy blastemal predominant subtype of Wilms tumor has to be classified as high risk tumor. Focal anaplasia has a better prognosis than diffuse anaplasia and will be classified as intermediate risk tumor.
Adolescent↗
[Visceral leishmaniasis. Personal observation and review of epidemiology, clinical aspects and therapy].
A 5 year old German girl contracted visceral leishmaniasis during a vacation in Spain, either 32 or 20 month prior to the manifestation of disease. She presented with fever, hepatosplenomegaly and pancytopenia. A bone marrow aspirate proved the diagnosis. Therapy with a pentavalent antimony drug brought about immediate improvement. Visceral leishmaniasis has to be suspected in individuals with fever, hepatosplenomegaly and pancytopenia who have resided in endemic areas (Mediterranean countries, India, East Africa, South America) during the previous years. If untreated, visceral leishmaniasis runs a fatal course. Therefore, early diagnosis by morphological and serological means and specific therapy with pentavalent antimony drugs are mandatory.
Animals↗
[Hypersensitivity to VM-26].
Life-threatening anaphylactic reactions to VM-26 are rare. In this report two patients with anaphylactic reactions after the first VM-26 applications in the German neuroblastoma therapy protocol GPO-NB-82 are described. After combination of VM-26 with dexamethasone, repetition of these reactions did not occur any more.
Adrenal Cortex Neoplasms↗
[Langerhans cell histiocytosis in childhood--results of the DAL-HX 83 study].
Owing to the unclear and mostly unknown etiology of Langerhans' cell Histiocytosis (LCH) and the unsatisfactory results in treating disseminated LCH a prospective multicentric study DAL-HX 83 was commenced, including 45 different clinics of West-Germany, Austria and Netherlands. From June 1st, 1983 to October 31st, 1986, 97 patients (pts) were involved in this study. 35 pts (9 females, 26 males, medium age 6 2/12 years, age range 0/12-14 2/12 years) suffering from localized disease (28x unifocal bone, 6x isolated skin, 1x isolated lymphnode involvement) were treated by surgery and/or radiation or were just kept in observation. 2 children (1 pt with primary localized bone lesion, 1 child with isolated skin rash) developed a new bone lesion after 1/2 year and 1 1/2 years respectively. 62 pts (33 females, 29 males, medium age 2 years, range 0/12-17 1/2 years) with previously untreated disseminated disease were assigned to 3 different risk groups (A, B and C) and were treated according to a standardized induction and risk adapted maintenance protocol. The whole treatment period was limited to 1 year. 19 pts with multifocal bone involvement (group A, medium age 6 1/2 years) were allocated to regimen A, 30 pts with bone and soft tissue involvement or soft tissue involvement alone (group B, medium age 1 8/12 years) to regimen B and 13 pts with dysfunction of the liver, lungs and/or haematopoietic system (group C, medium age 1 year) to regimen C. So far, 1 pt of group A (19 available pts) developed a new bone lesion after 10 months, another pt a suspicious bone involvement 16 months after diagnosis. A 4 months old girl of group B (27 available pts) died 11 months after diagnosis with progressive organ dysfunction, 2 pts are still alive with recurrent multifocal bone lesions and 1 pt achieved stable 2nd clinical remission after a local relapse (mediastinum). 4 pts of group C (11 available pts) died because of progressive disease between 5 days and 3 years after diagnosis, 3 pts are in partial remission after persistent and recurrent disease episodes. All the others are in clinical remission. The medium observation time of the whole group of pts with disseminated LCH is 1 9/12 years (range 0/12-3 5/12 years). The worst prognostic criteria were found to be the presence of organ dysfunction at diagnosis or its development during the course of disease and the age under two years.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
[Permanent central venous access in chronically-ill children].
15 patients aged 8 months to 18 years received implanted venous access catheters. Blood sampling and continuous infusions up to 52 days were performed via these devices. The systems were used for 18-166+ days and implanted for 18-635+ days. The complication rate was low and seems to be dependent on the experience of the caretaker. The systems are a valuable addition in the care of chronic sick children and offer new perspectives of therapy.
Adolescent↗
[Fluorescence cytophotometric DNA studies of Ewing and osteosarcomas].
The single-cell fluorescence cytometric data presented in this study basing on measurements on 6 osseous Ewing's-Sarcoma and 17 classical osteosarcoma are showing a mirrorlike behaviour to cytological and histological appearance. The cellular monotony in Ewing's-Sarcoma and the polymorphic appearance of osteosarcoma are represented by typical aneuploid DNA-histograms. Ewing's-Sarcoma histogram's show a large peak between the diploid and tetraploid region and little deviation to the octoploid value. The conventional osteosarcomas are characterised by a very polyploid and changeable DNA-histogram with variable blocks and peaks and deviation up to 34c. Special trends in the subtypes are remarkable, but depend on further investigations. DNA-measurements support objectivization of histological appearance on the one hand and the controlling of therapeutical responses on the other hand.
Adolescent↗
[Antineoplastic effectiveness and toxicity of idarubicin (4-demethoxy-daunorubicin) in recurrent acute leukemias in childhood].
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.
Adolescent↗
[Continuous doxorubicin infusions. A pilot study in young patients].
Eleven young patients with relapsed childhood malignancies received continuous infusions of 5-10 mg/m2/day doxorubicin. 30 infusions were given via a central venous access until signs of mucositis showed up (7-52 days). Other toxicity was low, both bone marrow depression and fever and neutropenia occurred in 7/30 and 5/30 courses of therapy, respectively. No signs of liver or cardiac toxicity were seen in these heavily pretreated patients. In 8/11 patients tumor regression was documented, though only two partial remission were noted. Continuous infusions of doxorubicin are an effective and relatively non-toxic treatment for relapsed childhood malignancies. Since this form of therapy enables good quality of life and medical care on ambulatory basis, a phase II-study of low-dose doxorubicin for relapsed tumors is justified.
Adolescent↗
[Side effects of antineoplastic therapy on the nervous system in children].
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Alkylating Agents↗
[Immunoglobulin administration as infection prevention in oncologic patients].
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.
Adolescent↗
[Role of chemotherapy in the treatment of malignant liver tumors in childhood].
Primary liver tumors in childhood should be resected totally whenever possible. The chances of long term survival of these patients improved considerably since postoperative chemotherapy has become obligatory. In the treatment of primarily inoperable tumors, initial chemotherapy is given to decrease the size of the tumor and thus achieve conditions for complete resection. For hepatoblastomas, chemotherapy should consist of vincristine, cyclophosphamid, adriamycin and actinomycin-D whereas the hepatocellular carcinoma responds best to anthracyclines. The most effective form of their application will have to be established.
Adult↗
Analysis of treatment efficiency of carboplatin and etoposide in combination with radical surgery in advanced and recurrent childhood hepatoblastoma: a report of the German Cooperative Pediatric Liver Tumor Study HB 89 and HB 94.
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.
Antineoplastic Combined Chemotherapy Protocols↗
Recancostat compositum therapy does not prevent tumor progression in young cancer patients.
Stimulated by the public discussion about an antimalignant effect of the supplement drug Recancostat compositum (200 mg glutathione, 40 mg cysteine, 50 mg anthocyanin) the drug was given in high doses to 16 young patients with intensively pretreated and measurable solid tumors for 1-30 weeks. In all patients the disease progressed, and they died 1-48 weeks following the start of the therapy. Side effects were not seen. This observation does not support the claim of an antitumor effect of Recancostat compositum.
Adolescent↗
Prevention of CNS recurrence in childhood ALL: results with reduced radiotherapy combined with CNS-directed chemotherapy in four consecutive ALL-BFM trials.
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-Münster (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.
Adolescent↗