[Farewell to Professor Dr. Werner Brandeis, Heidelberg and Professor Dr. Malte Neidhardt, Augsburg].
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Germany, West↗
Biomedical subjects
D Niethammer
Publications and source records attributed to D Niethammer.
[Effect of cranial irradiation on rate of recurrence in children with acute myeloid leukemia. Initial results of the AML-BFM-87 study. The AML-BFM Study Group].
Study AML-BFM-87 compared prospectively if cranial irradiation could be abandoned by adding two blocks of intensification with high dose ARA-C and VP-16 after consolidation and furthermore, improve prognosis compared to study -83. 210 children were enrolled in study AML-BFM-87 until March 31, 1991. 164 (78%) achieved complete remission. Probabilities for event-free survival (EFS) and event-free interval (EFI) of 5 years were: .45 (SD .04) and .57 (SD .05). In the first 2.5 years of the study irradiation was randomized (n = 31), selected or refused (n = 24). However, during this period irradiation was mandatory in patients with leukocyte count greater than 70,000/mm3, and also in children with initial CNS involvement. Since July 1989 prophylactic cranial irradiation was abandoned. Patients of the group with mandatory irradiation (n = 39) presented with more unfavourable risk parameters than the group of non-irradiated children, who were enrolled in the study after randomisation had been stopped. Nevertheless, results showed in randomized and selected patient groups as well as in the total cohort a longer relapse-free interval (RFI) in irradiated (n = 66) compared to non-irradiated (n = 94) patients (RFI of 5 years: .70, SD .04 vs. .51, SD .07, p less than .05). Relapses in non-irradiated children occurred mainly in the bone marrow and less often in the CNS. The increase in relapse rate was seen especially in non-irradiated patients of the low risk group as defined in study AML-BFM-83 (RFI: .40, SD .14 vs. .79, SD .09 with irradiation, p less than .01). In the high risk group, however, the differences were not significant. Our results suggest that cranial irradiation is an important part of therapy in childhood AML, and that the good prognosis of the low risk group in study AML-BFM-83 was probably based on the combination of intensive chemotherapy and cranial irradiation.
Antineoplastic Combined Chemotherapy Protocols↗
[Treatment of soft tissue sarcomas in childhood and adolescence: results of the CWS-81 multicenter therapy study].
344 previously untreated patients, under 19 years of age, with soft tissue sarcoma (STS) entered the first German STS Study, CWS-81. 218 of them with chemosensitive STS (Group A: rhabdomyosarcoma [RMS], synovial sarcoma, extraosseous Ewing's sarcoma, undifferentiated sarcoma and malignant peripheral neuroectodermal tumor) were evaluable for this analysis after a minimum potential follow-up of 6 years. A staging system based on the extent of disease, defined post-surgically, was used. The chemotherapy for stages I-III (VACA cycle) consisted of vincristine, dactinomycin, cyclophosphamide and doxorubicin. Patients with metastatic disease as well as stage III patients who failed to respond to VACA, were given ifosfamide instead of cyclophosphamide. The definitive local tumor control procedure for patients in stages II-III depended upon the tumor status at second-look surgery after 16 weeks of chemotherapy (no irradiation, 40Gy or 50Gy). The DFS rate after 5 years for group A was 57 +/- 4% and for patients with non-metastatic tumors (Stages I-III), 69 +/- 4%. There was no difference in prognosis between stages I and II (DFS rate 88 +/- 5% and 88 +/- 6% respectively). The DFS rate for stage III was 54 +/- 5% and for stage IV, 11 +/- 5%. Lack of local tumor control was the main cause of therapy failure: 10% of patients with localized disease never achieved CR, 18% relapsed locally. The most important prognostic factors were tumor size (p = .0002) and the degree of tumor regression after primary chemotherapy (p = .02).(ABSTRACT TRUNCATED AT 250 WORDS)
Antineoplastic Combined Chemotherapy Protocols↗
[Treatment of non-testicular germ cell tumors in children and adolescents with BEP and VIP: initial results of the MAKEI 89 therapy study].
The pilot protocol of the German Society of Pediatric Oncology for treatment of non testicular germ cell tumors was initiated in November 1987. The final protocol was started at 1. 1. 89. Different therapy was administered depending on histology, primary localisation or stage of tumors. Patients with malignant germ cell tumors such as dysgerminomas, embryonal carcinomas, yolk sac tumors or chorio carcinomas received BEP (Bleomycin 15 mg/m2/days 1-3, Etoposide 100 mg/m2/days 4-8, Cisplatinum 20 mg/m2/days 4-8), followed by VIP (Vinblastine 3 mg/m2/days 1 + 2, Ifosfamide 1500 mg/m2/days 1-5 including Mesna uroprotection and Cisplatinum 20 mg/m2/days 1-5). Patients with ovary tumors of stage 1 were treated with 3 courses of BEP, patients with ovary tumors stage II and extragonadal localisation received 3 courses of VIP in addition to 3 courses of BEP. In cases of extended tumors 4 courses of BEP were followed by delayed resection of tumors and 4 courses of VIP. Patients with intracranial germinomas were treated with 30 Gy of craniospinal radiation therapy and additional 15 Gy as a tumor boost. Since some cases of spinal extension were reported a spinal radiation therapy seems to be indispensable. Patients with intracranial embryonal carcinomas, yolk sac tumors or chorio carcinomas tumors were given 2 courses of BEP and VIP followed by 30 Gy of craniospinal radiation therapy and additional 20 Gy as a tumor boost. Patients with immature teratomas of the ovary grade 1-3 and grade 3 of tumors with extragonadal localisation were treated with 3 courses of BEP after resection of tumors. Until 1. 1. 1991 92 patients were reported to the study--27 with intracranial and 65 with extracranial primary localisation of tumors. 43 patients suffered from teratomas (including 20 immature teratomas grade 1-3), 18 from germinomas (seminomas/dysgerminomas) and 31 from malignant non-seminomatous germ cell tumors. After an observation period of 29 months disease-free survival rate was 80% (79/92 patients, Kaplan-Meier Statistics). Outcome of intracranial tumors was death or relapse in 2/9 patients with malignant non-seminomatous germ cell tumors, in 2/14 patients with intracranial germinomas, in 2/4 patients with teratomas. Patients with extracranial localisation of tumors suffered from death or relapse in 1/21 cases with non-seminomatous tumors, in 0/4 cases with dysgerminomas and 5/39 cases with teratomas. During pilot study one infant with a malignant non-seminomatous germ cell tumor died of a pneumopathia. Therefore infants treated according to the final protocol did not receive Bleomycin.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
[The role of interferons in neuroblastoma. 1: Antiproliferative effects].
Antiproliferative effects of interferon alpha, beta and gamma were investigated on several human neuroblastoma cell lines using the soft agar colony forming assay and the MTT-test. Investigations were carried out in order to prove whether there is any relationship between antiproliferative effects, inhibition of N-myc expression and the 2-5A system. Growth of neuroblastoma cells was inhibited by all three kinds of interferons in a concentration-dependent manner, however, rather high concentrations were necessary in some cell lines. Expression of N-myc oncogen was not inhibited by interferon-beta and no relationship between antiproliferative effects and the 2-5A system was observed. A vector containing a small N-myc fragment in antisense direction was constructed and transferred into the interferon insensitive human neuroblastoma cell line LS. After transformation, LS cells became sensitive to interferon beta: Proliferation as well as N-myc expression were inhibited and these processes are most probably associated with activation of the 2-5A system.
2',5'-Oligoadenylate Synthetase↗
[The role of interferons in neuroblastoma. 2: Immunomodulatory effects].
The role of Interferon-gamma (IFN-gamma) in the immunotherapy of neuroblastoma was investigated. In vitro experiments showed that IFN-gamma augments the cytotoxicity of Natural Killer (NK) cells and of interleukin 2 (IL-2)-activated NK (LAK) cells against neuroblastoma target cells. Incubation of the neuroblastoma cells with IFN-gamma resulted in an increased susceptibility of these target cells to NK and LAK cells. Additionally, the IFN-gamma-treated neuroblastoma cells showed an increased susceptibility to the antibody-dependent cellular cytotoxicity (ADCC). In patients who have been treated with continuous infusions of IL-2, IL-2-induced secretion of IFN-gamma was detected by measuring the elevation of the 2-5 A synthetase activity in peripheral mononuclear cells or the 2-5 A oligoadenylates in the serum, although IFN-gamma itself was not detectable. From these results we conclude that IFN-gamma may play an important role in the immunotherapy of neuroblastoma in combination with IL-2 and/or with monoclonal antibodies.
Antibody-Dependent Cell Cytotoxicity↗
The role of chemotherapy in the treatment of children with neuroblastoma stage IV: the GPO (German Pediatric Oncology Society) experience.
340 consecutive patients with neuroblastoma stage IV were analyzed for the possible impact of chemotherapy on general condition, remission status, event free survival and survival. The children entered the trials NB 79, NB 82 and NB 85 of the German Pediatric Oncology Society (GPO). The patients did benefit from chemotherapy by considerable improvement of the general condition, by achievement of 30-40% complete and 60-70% partial remissions. The event free survival (EFS) rate 5-8 years after diagnosis was 13% for all 299 protocol patients, the survival (S) rate 10%. The median/mean EFS time were 11.6/23.8 months, the median/mean S time 17.0/29.4 months. The use of response rates as early predictors for long term survival is challenged. Addition of PCVm (cisplatinum, cyclophosphamide, Vm 26) to ACVD (adriamycine, cyclophosphamide, vincristine, dacarbazine) in trial NB 82 resulted in an improvement of the long term EFS rate from 5% to 18% (S rates 7----21%). The introduction of IVp (ifosfamide, VP16) and increase of doses (cisplatinum, Vm 26) did not further improve the results. Maintenance therapy (NB 82) revealed a positive influence on the outcome. Shorter intervals for realization of chemotherapy were associated with a trend for better EFS (NB 85). Although the group of children with bone marrow transplantation showed better EFS and S data compared to the unselected chemotherapy group, the advantage was less clear if matched pairs (remission status at the time of BMT) were compared.(ABSTRACT TRUNCATED AT 250 WORDS)
Antineoplastic Combined Chemotherapy Protocols↗
[Intensive combined drug therapy and beta-interferon in the treatment of children with metastasizing neuroblastoma: GPO-NB 79/82 study].
From June 1979 to June 1982 72 children with metastatic neuroblastoma older than 1 year of age at diagnosis were treated according to the protocol NB 79 of the German Society for Paediatric Oncology. The chemotherapy included three cycles of adriamycine, cyclophosphamide, vincristine, dacarbazine and five cycles of adriamycine and cyclophosphamide. 34 patients were randomized for additional beta-Interferon (Fiblaferon) treatment (10(5) U/kg daily for 3 weeks followed by 3 times a week for 21 weeks). 38 patients were not treated with Fiblaferon. The response rate was 96% including 35% complete and 61% partial remissions. Preoperative chemotherapy improved remarkably the resectability of the primary tumor without enhancing complication rates. The cumulative proportion surviving was 21% for the interferon group and 6% for the patients not treated with interferon. The cumulative recurrence free survival rate, however, was 5% for both groups. The median survival time was 19 months and the median recurrence free survival time 10 months. A serious side effect of chemotherapy was bone marrow depression (73%) resulting in 1 week delay of drug administration per cycle. The median of administered drug dosages was 87-100% of the recommended dosages. Side effects of beta-Interferon commonly decreased with time and were fever reactions (55%), shaking chills (29%), cardiovascular reactions (16%).(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
[Indications for autologous bone marrow transplantation in pediatric oncology. Results of the 5th meeting of experts of the Kind-Philipp Foundation, Riesensburg, November 1988].
In November 1988 experts from Europe and the United States of America have met at the Reisensburg near Ulm. The aim of this meeting was to discuss the value of autologous bone marrow transplantation for children with various malignant diseases. The paper summerizes the results of the different sessions. In this way the value of this therapeutic procedure at present time is defined. This is meant as help for those pediatricians who treat children with malignant diseases.
Bone Marrow Transplantation↗
[Special supportive measures in pediatric oncology].
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Bone Marrow Transplantation↗
[Results of the treatment of non-rhabdomyosarcomatous soft tissue neoplasms within the scope of the CWS 81 study].
347 children with all types of soft tissue sarcoma (STS) have been entered between 1981 and April 1986 into the CWS-81 study. Excluding 229 patients with rhabdomyosarcoma, 118 patients with other STS were analysed in the histological subgroups, separately. 33 synovial sarcomas (SyS), 15 undifferentiated sarcomas (US) and 13 extrasceletal Ewing's sarcoma (EES) were treated with a multimodale trial including chemotherapy and radiotherapy after initial not-mutilating resection or biopsy only, Relapse-free survival rate by Kaplan-Meier was 66% in SyS, 48% in EES and 38% in US, respectively. Patients treated according to the guidelines of the CWS-protocol showed better prognosis than patients with major protocol violations or patients with recurrence when entered into the trial. In SyS only 2 of the 7 patients with recurrence developed metastases. The tumor response rate within 7-9 weeks chemotherapy exclusively given was 71% in patients with stage III and IV. Non-responding tumors to chemotherapy had bad prognosis, irrespective of histological subtype or further treatment. EES and US developed earlier recurrence and more often metastases than SyS or rhabdomyosarcomas. The administered VACA-chemotherapy seems not to be very effective in EES and US. In all other varieties of STS recurrence at the primary site assumed relatively greater importance. Chemotherapy and radiation were not administered in all patients. Fibrosarcoma (FS) was diagnosed in 13 patients. Six of these were entered in the trial at the time of local recurrence and 4 of these 6 relapsed again locally, one with metastasis concurrently.(ABSTRACT TRUNCATED AT 250 WORDS)
Antineoplastic Combined Chemotherapy Protocols↗
[Bone marrow transplantation in leukemias in the absence of HLA-identical siblings--results of the 4th meeting of experts of the Kind-Philipp Foundation at Reisenburg 11/12 November 1985].
During recent years allogeneic bone marrow transplantation has been shown to be of clear value in the therapy of childhood leukemia. Presently the availability of an HLA identical sibling is necessary. Recently there are several attempts to pass this natural barrier. Possible alternatives are autologous transplantation or the use of an nonidentical family member or an identical unrelated person as a donor. Members of 17 bone marrow transplantation teams of the western world discussed during two days the various possibilities and the results obtained up to now. The paper reflects the state of the art as it was represented during the meeting. This is meant to help advice patients with leukemia and their parents on the further therapeutic proceedings.
Bone Marrow Transplantation↗
[Current results of cooperative AML therapy studies in children: BFM-78 and 83].
271 children with AML entered the cooperative studies BFM-78 (151 pat.) and BFM-83 (120 pat.) since Dec. 1, 1978. In the second study BFM-83 the 8-10 week intensive induction/consolidation therapy of study BFM-78 was preceded by an 8-day intensive therapy consisting of cytosine arabinoside, daunorubicin and VP-16. 10 children died prior to starting the protocol therapy from hemorrhage and/or leukostasis. 80% of the 261 protocol patients achieved a complete remission. 7% were early deaths by hemorrhage and/or leukostasis 3% died of other complications. 10% were partial or nonresponders. 54 relapses, 11 with CNS involvement have occurred in study BFM-78 after a follow up of 2.10-6.7 years (median 4.10 yrs.). The life table probabilities for event free survival (EFS) and event free interval (EFI) after 6.7 years are 37% (SD 4%) and 47% (SD 5%) respectively. The results of study BFM-83 after a follow up of 0.3-2.8 years (median 1.8 yrs.) are: 23 relapses, EFS 40% (SD 10%) and EFI 48% (SD 12%). So far, the overall results of both studies are nearly identical. The analyses of the prognostic factors show that initial hyperleukocytosis (greater than or equal to 100 X 10(3)/mm3) represents a high risk for early fatal hemorrhage and/or leukostasis, for nonresponse and for the incidence of relapses. Initial deaths caused by hemorrhage and/or leukostasis occur also significantly more often in patients with M5-subtype and extramedullary organ involvement. Additional strategies for achieving a better prognosis in high risk patients are necessary.
Adolescent↗
[Results of treatment of rhabdomyosarcomas (RMS) in children. A report of the Cooperative Soft Tissue Sarcoma Study (CWS-81) of the Society of Pediatric Oncology].
This analysis refers to 129 children with RMS who were treated between 1981 and 1985 according to the protocol guidelines of the CWS-81 study. The duration of chemotherapy depended on the initial post-operative stage. Patients with stage I and IIA were not to receive any radiotherapy, and patients with primary stage III were treated according to the results of a 16-week chemotherapy treatment: either without radiation (stage Ipc), or with radiotherapy using 40 Gy (stage (IIpc) or 50 Gy (stage IIIpc). The median time of observation was 27 months (Juni 1985). The essential results of the study are as follow: RMS of the extremities in stages I and IIA need radiotherapy, contrary to all other localisations with the same stages. Patients with RMS stage III who are tumor-free after initial chemotherapy (histologically checked) do not need radiotherapy. Patients with microscopic residue (IIpc) or macroscopic residue (IIIpc) after pretreatment showed no difference in their local relapse rate, whereas metastases were found only in the group having macroscopic tumor residue up to week 16. An additional examination of this study observed tumor response during initial chemotherapy and its relationship to prognosis. This analysis showed that the degree of tumor regression per unit of time permits the most favorable prognostic statement. Patients with clinical complete remission after 7/9 weeks showed a 100% relapse-free chance of survival, independent of localisation, tumor size or histological subtype. Those with a tumor reduction of greater than 2/3 but no complete remission showed 67% chance of survival, and those with greater than 1/3-2/3 tumor reduction had 25%. Tumor response kinetics under initial chemotherapy allows better individual therapy in the future. The overall result of the study concerning localisation and stage corresponds to that of the IRS I and II studies. Patients with undifferentiated sarcomas, extraossary Ewing's sarcoma and synovial sarcomas can be treated according to the same principles as RMS, since no significant differences in prognosis could be found.
Antineoplastic Combined Chemotherapy Protocols↗
[Initial experiences in the treatment of children with metastatic and recurrent neuroblastoma using meta-iodobenzylguanidine].
At four involved hospitals 16 children were treated with Metaiodobenzylguanidine (131J-MIBG). These children had a relapse of neuroblastoma stage III or IV or did not respond sufficiently to chemotherapy. In 10 children extreme bone pain disappeared and they became free of fever during the MIBG-treatment. 10 children responded to the therapy demonstrated either by decrease of the solid tumor part or by decrease of catecholamines in urine or plasma or by decrease of bone-marrow involvement. One patient reached a complete remission continuing up to present time (longer than 180 days). 9 patients died meanwhile of tumor progression. 131J-MIBG is an effective instrument, to get a decrease of the tumor up to a complete remission in extensively pretreated patients with tumor relapse, which are refractory to chemotherapy.
3-Iodobenzylguanidine↗
[Significance of procarbazine in the chemotherapy of Hodgkin's disease--a report of the Cooperative Therapy Study DAL-HD-85].
It was the objective of the DAL study HD-85 to examine the possibility of a reduction of chemotherapy, compared to the study HD-82 which had applied a combined treatment strategy resulting in a relapse rate of only 2.5% after 4 years, and a proportion of intercurrent deaths of 1.5%, in a total of 203 patients. Procarbazine was eliminated in the OPPA-therapy (OPA) and replaced by methotrexate in the COPP-cycles (COMP). Chemotherapy consisted in 2 cycles of OPA for stage I/IIA (group 1), 2 cycles of OPA and 2 cycles of COMP for stage IIB/IIIA (including IEA/IIEA) (group 2), and 2 cycles of OPA and 4 cycles of COMP for stage IIIB/IV (group 3). The subsequent radiotherapy was limited to the initially involved fields, the dosage of 35, 30 or 25 Gy depending on the extent of chemotherapy. Regions showing incomplete tumor regression after chemotherapy received another 5 Gy, in patients of groups 2 and 3. Between Jan. 1985 to Nov. 1986, 103 children with Hodgkin's disease from 42 participating hospitals were enrolled in this study. 98 patients were treated according to protocol (59 boys, 39 girls). A specific strategy for the selective indication of laparotomy and splenectomy was applied. With this strategy no laparotomy was performed in 39/98 patients (40%). 67 patients (68%) retained their spleen. 4 patients showed progression of the disease under chemotherapy, all others achieved remission. 16 patients relapsed before Dec. 31, 1987. So far no child of this study has died.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Acute lymphoblastic leukemia therapy study BFM 79/81 in children and adolescents: intensified reinduction therapy for patients with different risk for relapse].
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Adolescent↗
[Neuroblastoma study NBL 79 of the German Society for Pediatric Oncology. Report after 2 years].
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Child↗