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D Niethammer

Publications and source records attributed to D Niethammer.

At least 343 records · Page 19Linked to original sources
PubMedDate not supplied

[Adult form of chronic myelogenous leukemia in childhood--a retrospective analysis of 20 patients].

The initial findings and the course of 20 children and adolescents with adult CML from 10 children hospitals were analyzed retrospectively. The Philadelphia chromosome was found in 18 patients. Initial findings, the course and the prognosis were similar to those published from adult patients. 7 of the 11 children who received chemotherapy alone are still alive with a median survival time of 26 months (range: 14 to 68 months). One patient survived the third blast crisis. For 9 children with a bone marrow transplantation during the chronic phase (median time before transplantation 30 months) the follow-up of 7 months is still too short. 4 of these patients died following graft versus host reaction, 5 show no signs of a renewed occurrence of CML so far. Since CML is rare in children, there is little large scale experience. Hence, there is an urgent need for the prospective and cooperative study of these patients.

Adolescent↗
PubMedDate not supplied

[Acute myelogenous leukemia in children: results of the cooperative BFM-78 therapy study after 3 3/4 years].

Between December, 1978, and October, 1982, 151 children with acute myelogenous leukemia from 30 pediatric clinics entered the cooperative study. The treatment consisted of a 10-week intensive induction therapy and a subsequent maintenance therapy, which is terminated for children in complete continuous remission after 2 years. The induction treatment during the first 4 weeks consisted of a combination of prednisone, 6-thioguanine (TG), vincristine, adriamycin (ADR) and cytosine-arabinoside (ARA-C). In the following 4 weeks i.v. cyclophosphamide, i.th. methotrexate and prophylactic cranial irradiation were administered in addition to TG, ARA-C and ADR. 119 of the 151 patients (79%) achieved complete remission. 13 children (9%) died of early hemorrhages, 2 of them before onset of therapy. 5 patients died initially of other complications, another 6 after remission has been achieved. 13 children did not respond or responded poorly to the induction therapy. So far, 40 relapses occurred, mainly in the bone marrow. In 6 relapses the central nervous system was involved. The probability for a continuous complete remission for the total group is 0.41 +/- 0.05 (life table analysis) and for the total group 0.56 +/- 0.06 after 45 months. The corresponding probability for survival after 46 months are 0.43 +/- 0.06 for the remission group. The risk for occurrence of early fatal hemorrhages was higher in children with acute monocytic leukemia than in the other morphological subtypes. An initial leukocyte count of more than 100,000/microliters was found significantly more often in patients who did not achieve remission (early deaths and nonresponders) than in children of the remission group. So far, no factors could be identified which influence the risk for relapse. The present results of the study allow the conclusion, that with the applied treatment strategy it is possible to achieve not only in a high portion of children with AML remission but also to improve the chances for long-time remission and perhaps cure.

Adolescent↗
PubMedDate not supplied

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↗
PubMedDate not supplied

[After-care of children and young adults surviving cancer. Initial recommendations by the late sequelae study group].

An increasing number of children suffering from cancer has been treated successfully during the last 25 years using therapy protocols of the Gesellschaft für Pädiatrische Onkologie und Hämatologie. The patients had to undergo an interdisciplinary treatment modality and a mostly intensive chemotherapy. Late effects could result from this approach for the now 20,000 survivors in the Federal Republik of Germany. The executive committee of the GPOH founded a working group for the detection of late effects stretching over all therapy studies. The first report of this group describes a spectrum of relevant late effects and proposes investigations for their detection.

Adolescent↗
PubMedDate not supplied

[Reducing radiation dosage to 20-30 Gy in combined chemo-/radiotherapy of Hodgkin's disease in childhood. A report of the cooperative DAL-HD-87 therapy study].

UNLABELLED: The main objective of the multicenter study DAL-HD-87 was to evaluate for the involved-field irradiation a dose reduction by 5 Gy compared with the precursor studies HD-82 and HD-85. Moreover, the decisional strategy for selective laparotomy developed on the basis of retrospective analyses in study HD-82 was to be tested in a prospective design. Chemotherapy in group 1 (stages I, IIA) consisted in 2 OPA cycles (vincristine, prednisone, adriamycin). Group 2 (stages IIEA, IIB, IIIA) received 2 x OPA + 2 x COP(P), and group 3 (stages IIEB, IIIB, IV) 2 x OPPA (with procarbacine) + 4 x COP(P). For the subsequent radiotherapy, doses of 30, 25, and 20 Gy respectively were applied in the 3 groups. Fields with incomplete lymphoma regression were to receive an additional boost of 5-10 Gy. -Exploratory laparotomy was considered indicated in the event of abnormal findings in abdominal CT/ultrasonography and/or enlargement of lymph nodes at the pulmonary hilus. RESULTS: From Dec. 1986 to Sept. 1990, 204 pts from 51 centres were enrolled in the study. 196 were evaluable. 109 pts (55.6%) were laparotomized, 58 (29.6%) splenectomized. The accuracy for the prediction of an abdominal involvement was 72.3% in case of abnormal findings in abdominal CT/ultrasound but only 36.4% in case of enlarged lymph nodes at the pulmonary hilus without abdominal abnormalities. 91.2% of the removed spleens were proven involved. -2 out of 196 pts suffered progression under treatment, and 22 relapsed (as of 1 Jan, 1994). 6 pts died, 4 of whom succumbed to Hodgkin's disease, and 2 to intercurrent infections. 2 pts in first remission developed a secondary malignancy, namely 1 malignant histiocytoma in radiation field and 1 ANLL. Another patient developed a thyroid carcinoma following salvage therapy for a relapse. The probabilities of event-free survival (EFS) and survival after 7 years are for the total group: 85% and 97%, in group 1: 84% and 99%, in group 2: 82% and 93%, and group 3: 89% and 95%. Comparison with the precursor studies HD-82 and HD-85 reveals that the dose reduction in radiotherapy has not affected the results. Differences in EFS are exclusively correlated with changes in chemotherapy.

Adolescent↗
PubMedDate not supplied

[Improved local tumor control by early and risk-adjusted use of radiotherapy in primary non-resectable rhabdomyosarcomas: results of CWS 81 and 86 studies].

Since the lack of local tumor control was a major cause of therapy failure in the CWS-81 Study, the concept of the definitive local tumor control in patients with primary non-resectable RMS has been changed. In the CWS-81 Study RT was stratified according to the results of SL surgery at week 16-20 (after 2 cycles of CT), given only to patients who at this time stage had still microscopic or macroscopic tumor residuals. In the CWS-86 Study irradiation was given prior to SL surgery after one cycle of CT (7-10 weeks). The cumulative dose was stratified according to the degree of tumor volume reduction (32 Gy and 54.4 Gy) and given simultaneous to the second CT. The single dose was reduced (1.6 Gy) and given twice a day (accelerated hyperfractionation). This analysis excluded patients with parameningeal and extremity primaries since this group had special RT recommendation in both studies. 62% of patients had been irradiated in the CWS 81 Study and 70% in the CWS 86. The local tumor control improved dramatically in the CWS-86 Study in the group of patients who had been irradiated prior to SL surgery and still had macroscopic residues at the start of RT (rate of local tumor control 25% vs. 95%, p < .001). The average RT dose for this group was even lower in the CWS-86 Study (38.8 vs. 40 Gy). In the patients who were irradiated in clinical remission, no major change in local tumor control between studies was observed (CWS 81 82% vs. 75% CWS 86).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Human gammadelta T lymphocytes exert natural and IL-2-induced cytotoxicity to neuroblastoma cells.

Human gammadelta T lymphocytes play an important role in nonadaptive reactions to infection and early tumor defense. This is the first report that freshly isolated, native gammadelta T cells of some healthy donors can kill human neuroblastoma cells to varying degrees. Their killing ability was increased and maintained during expansion and cultivation with interleukin-2 (IL-2; 400 IU/mL) for as long as 30 days (100% specific lysis at an effector-to-target cell (E:T) ratio of 20:1). gammadelta T lymphocytes without this spontaneous killing ability gained a specific cytolytic activity of 81% +/- 10.4% SD after stimulation with IL-2 for 24 hours. gammadelta cells were isolated from peripheral blood by positive enrichment (using a magnetic cell sorting system; purity, 95.2% +/- 3.2% SD, n = 21). High natural cytotoxic activity against human neuroblastoma cell lines (>50% specific lysis at an E:T ratio of 20:1) was exhibited by one of 11 donors, whereas two of 11 showed medium cytotoxicity (30% to 50% specific lysis). Eight of 11 donors showed very slight or no lytic activity against human neuroblastoma cells (<30% specific lysis). gammadelta T cells were also cytotoxic against Daudi (32.7% specific lysis at an E:T ratio of 20:1), Raji (10.3%), Colo 205 (23.1%), A 204 (54%), K 562 (100%), and SK-N-MC (100%) cells. Isolated gammadelta T cells were grown in Iscove modified Dulbecco medium with IL-2 (400 IU/mL). Increased cell proliferation (38.5% to 182%) was induced with phytohemagglutinin, IL-15, Clodronat, OKT3, or various combinations of these. Results of cold target inhibition assays suggest a natural killer-like activity of the gammadelta T-cell killing mechanism. Peptidase or papain render neuroblastoma cells unsusceptible to gammadelta T-cell killing, suggesting the involvement of antigen peptide(s) in the process of neuroblastoma cell killing. Treatment with acid phosphatase reduced specific lysis by 66.5% +/- 34.1% SD, which suggests a binding to phosphorylated neuroblastoma cell-surface structures in the killing mechanism of gammadelta T cells. Heat shock did not affect the extent of neuroblastoma killing by gammadelta cells. Recognition of neuroblastoma cells by gammadelta cytotoxic T lymphocytes is negatively regulated by major histocompatibility complex I receptors. Evidence for natural and inducible cell cytotoxicity of gammadelta T cells against human neuroblastoma cells, easy propagation, purification, and missing alloreactivity in mixed lymphocytes cultures indicates a role for this subpopulation of T lymphocytes in adoptive immunotherapy.

Adult↗
PubMedDate not supplied

Orointestinal yeast colonization of paediatric oncologic patients during antifungal prophylaxis: results of quantitative culture and Candida serology and comparison of three polyenes.

The orointestinal yeast colonization of 46 children with newly diagnosed malignancies was studied prospectively and longitudinally with quantitative cultures during remission induction chemotherapy. The initial colonization rate was 24%; only 28% of the patients remained free of yeasts during their entire treatment although all of them continuously received oral polyenes as antifungal prophylaxis. A randomized comparison of natamycin (suspension, lozenges), nystatin (suspension) and amphotericin B (suspension, lozenges) failed due to serious problems with patient compliance. Natamycin was best accepted by the patients and natamycin lozenges were the most efficacious drug in the oral cavity. The effectivity of the suspensions of nystatin and amphotericin B was similar; both were equally efficacious in the oral cavity and the gut. Assessment of faecal polyene concentrations by HPLC showed the highest results for amphotericin B (mean 6808 microgram(-1)). Regularly performed Candida serology (indirect haemagglutination, indirect immunofluorescence and immunodiffusion precipitation) revealed significant titre increases in 63% of the patients. In six cases, the synopsis of clinical picture, culture and serology strongly suggested systemic yeast invasion.

Adolescent↗
PubMedDate not supplied

Orointestinal yeast colonization of paediatric bone marrow transplant recipients: surveillance by quantitative culture and serology.

We quantitatively studied the orointestinal yeast colonization of 15 consecutive paediatric patients who underwent 16 bone marrow transplantations (BMT). Cultures were performed initially, longitudinally weekly during the period of aplasia (in-patient treatment) and, if possible, also during out-patient follow-up. With one exception, all patients received fluconazole as antifungal prophylaxis. Patients remained free of yeasts during the complete observation period only in six out of 16 cases (38%). Non-albicans species of Candida were isolated in six out of 16 cases (38%), mainly C. glabrata (five out of 16; 31%). All of these patients had undergone allogeneic BMT. In one case, there was indirect evidence of systemic invasion by C. glabrata. Even combined prophylaxis with fluconazole and and amphotericin B suspension could not reliably prevent yeast colonization but this combination at present appears to be the optimal regime. Regular concomitant Candida serology (determination of specific antibodies by three methods) proved to be a valuable additional surveillance method.

Adolescent↗
PubMedDate not supplied

Retrospective analysis of yeast colonization and infections in paediatric bone marrow transplant recipients.

Sixty-four paediatric patients who underwent allogeneic (n = 35), autologous (n = 28) or syngeneic (n = 1) bone marrow transplantation (BMT) between 1992 and 1994 were evaluated retrospectively. As antifungal prophylaxis, all patients received amphotericin B tablets and 62 of 64 (96.9%) received oral fluconazole. Weekly surveillance cultures revealed fungal colonization in 35 patients (54.7%). Six patients (9.4%) were colonized before BMT only, 17 (26.6%) after BMT only and 12 (18.8%) both before and after BMT. Candida albicans was the most frequently isolated fungus [21 of 46 fungal isolates (45.7%)], followed by C. glabrata [14 isolates (30.4%)]. Non-albicans species of Candida were most frequently isolated after BMT from the faeces, often in high numbers. Autologous marrow recipients had a higher fungal colonization rate both before and after BMT than allogeneic marrow recipients. One patient suffered from invasive pulmonary aspergillosis after BMT. No fungaemias or deep-seated yeast infections were observed. Six of the seven patients who had to be treated with intravenous amphotericin B because of antibiotic-refractory fever had undergone autologous BMT. Multivariate analysis of various parameters showed only pre-BMT yeast colonization to be independently associated with post-BMT colonization. Thus, systemic mycoses occurred only rarely in this study population; however yeast colonization after BMT (especially with non-albicans species) was a frequent event in spite of double prophylaxis with oral amphotericin B and fluconazole.

Adolescent↗
PubMedDate not supplied

Report on the international workshop of the Kind Philipp Foundation on late effects after bone marrow transplantation in childhood malignancies.

This report is a short summary of an international workshop on late effects after bone marrow transplantation in pediatric patients. Main topics of the report are chronic GVHD and immune reconstitution and the late effects of this kind of treatment on growth, respiratory function, the endocrinological system, teeth, and eyes. The development of secondary tumors is discussed as well as the influences on the central nervous system and behavior of children.

Bone Marrow Transplantation↗
PubMedDate not supplied

Expression analysis of multidrug resistance associated genes in neuroblastomas.

In a series of 40 neuroblastomas we analyzed the relative mRNA levels of the MDR associated genes encoding MDR1/P-glycoprotein (MDR1), multidrug resistance associated protein (MRP), lung cancer resistance related protein (LRP) and topoisomerase IIalpha (TOPO IIalpha) by cDNA-PCR. Cyclin A (CYCA) was included to examine cellular proliferation activity. MYCN gene expression was analyzed as it was recently shown to be associated with enhanced MRP gene expression in neuroblastomas. We found that tumors with MYCN gene amplification exhibit significantly increased MYCN and MRP gene expression levels. Tumors with an allelic loss of the chromosomal 1p region showed significant (P<0.05) lower MDR1 gene expression (MDR1: 50+/-29, n=4) than tumors without (MDR1: 117+/-81, P<0.05, n=36). Moreover, significant positive correlations were found for MYCN/TOPO IIalpha (P<0.0001), MYCN/CYCA (P<0.05), TOPO IIalpha/CYCA (P<0.01), MRP/CYCA (P<0.0001) and MRP/LRP (P<0.05). Our results give evidence that MDR in neuroblastomas might be caused by multiple resistance factors and that a higher proliferation rate of neuroblastoma cells possibly based on altered MYCN gene expression is associated with enhanced MRP, CYCA and TOPO IIalpha gene expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Effect of amifostine on neuroblastoma during high dose chemotherapy: in vivo and in vitro investigations.

Amifostine (Ethyol, WR-2721) has been clinically used in combination with high dose therapy of neuroblastoma stage 4 with melphalan, carboplatin and VP-16 in 14 patients. The amifostine group was compared to a historical control group of 24 comparably-treated patients. There were no significant differences regarding the time of hematological recovery, the duration of hospitalization, the duration of antibiotic treatment and the extent of renal toxicity. However, in contrast to four patients of the control group, no patient in the amifostine group developed such severe mucositis that artificial ventilation became necessary. Pretreatment of neuroblastoma cell lines for 30 minutes with amifostine and the free thiol(WR-1065) did not reduce the cytotoxic effects of melphalan, carboplatin and VP-16. Evidence was obtained that the uptake of the activated thiol could be achieved by a polyamine transporter. Taken together, the data do not support the use of amifostine in high dose chemotherapy of neuroblastoma prior to autologous stem cell transplantation. However, amifostine may be more effective in conventional neuroblastoma therapy where protection of bone marrow stem cells is necessary.

Amifostine↗
PubMedDate not supplied

Treatment of neuroblastoma with [131I]metaiodobenzylguanidine: long-term results in 25 patients.

From 1984 to 1990 we have treated altogether 25 children with [131I]metaiodobenzylguanidine (131I-MIBG) for a refractory, relapsed or metastasized neuroblastoma. Three children had stage III and 22 children had stage IV of the disease; at diagnosis their ages were between 4 months and 10 years. Children with stage III disease had at diagnosis a median age of 3.0 years and at treatment 3.8 years. After first-line chemotherapy 2 children had achieved a complete remission (CR), while in 1 child the tumor did not respond (NR) to the initial treatment. At the time of 131I-MIBG treatment 2 children had relapsed and in the other one no further response was achievable. The children were treated by a 13.5 +/- 12.9 mCi/kg BW per course with a mean total dose of 280.7 +/- 243.9 mCi. One child achieved CR by 131I-MIBG alone, while in 2 cases no measurable success was observed. All 3 children were treated additionally by surgery, chemotherapy and bone marrow transplantation (BMT). Two children have died but one is alive and in CR. The 22 children with stage IV disease were treated in two different study groups. In group A, 14 children were studied for side-effects and response to 131I-MIBG. All children were pretreated with standard chemotherapy. Five were treated in relapse, 5 in progression and 3 at a refractory state of the disease; only 1 child was in complete remission when being treated with 131I-MIBG. Group A patients were treated with a mean of 2.4 courses, with 10.3 mCi/kg BW for each course.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗
PubMedDate not supplied

Ascorbic acid induces lipid peroxidation on neuroectodermal SK-N-LO cells with high endogenous ferritin content and loaded with MAb-ferritin immunoconjugates.

Neuroblasma-and other malignant cells often contain elevated amounts of iron-rich ferritin and H2O2 and may therefore be a potential target for pro-oxidative effects of ascorbic acid (AA), generating cytotoxic products e.g. by lipid peroxidation (LPO). The influence of H2O2 and iron, either in its free form or bound to ferritin, on AA induced LPO was first investigated using erythrocyte ghosts as a model system. Results of these experiments showed that AA induced LPO not only in the presence of free available iron but also in the presence of ferritin. Similarly, AA induced significant LPO in neuroectodermal SK-N-LO cells with elevated intracellular ferritin levels. These LPO promoting effects of ferritin in the presence of AA on SK-N-LO cells could also be observed using ferritin-immunoconjugates: for this purpose, ferritin was bound to human monoclonal antibodies (MAb-ferritin) recognizing ganglioside GD2 which is present in large quantities on cell surfaces of SK-N-LO and many neuroblastoma cells. We conclude that the pro-oxidative effects of AA could be exploited in the treatment of ferritin rich neuroblastoma in combination with chemotherapy or with MAb-ferritin immunoconjugates.

Antibodies, Monoclonal↗
PubMedDate not supplied

Uptake and cytotoxicity of ascorbic acid and dehydroascorbic acid in neuroblastoma (SK-N-SH) and neuroectodermal (SK-N-LO) cells.

Ascorbic acid (AA) was found to be cytotoxic to neuroblastoma cells in vitro and in vivo. In the present, study we investigated whether the reduced--(AA) or oxidized form (dehydroascorbic acid, DhAA) and its rapidly formed metabolites were the main cytotoxic agents. In neuroblastoma SK-N-SH cells, AA was found to be more cytotoxic than DhAA, although considerably higher amounts of [14C]DhAA than of [14C]AA were incorporated. In contrast, SK-N-LO cells derived from neuroectodermal tissue in fact showed a similar uptake but were much less injured by both substances. We observed that uptake of [14C]AA and [14C]DhAA was impaired in the presence of dithiothreitol and glutathione. Once inside the cell, [14C]DhAA was partially reduced to [14C]AA. From these data we conclude first that at least part of AA is oxidized prior to its uptake, and second that the reduced form of AA and perhaps ascorbyl radicals but not DhAA or its metabolites are the most important forms in mediating cytotoxic reactions in neuroblastoma cells. Furthermore, the results strengthen the previous assumption that AA acts as a pro-oxidant in neuroblastoma cells and supports its use in the treatment of neuroblastoma, especially in combination with existing chemotherapeutics.

Ascorbic Acid↗