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T Klingebiel

Publications and source records attributed to T Klingebiel.

At least 181 records · Page 10Linked to original sources
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Immunotherapy in children: report from the Reisensburg-Symposium October 20-22, 2004 and recent advances.

Immunotherapy of childhood malignancies has a magic aura of promising an easy way to cure. It is not only the public, but also the medical community, which has caused this hope. Therefore, it was worthwhile to bring together a panel of experts working in the field of immunotherapy in order to discuss ongoing projects, and to show hopes and disappointments. The result was a fascinating symposium sponsored by The Kind Philipp Leukemia Foundation (Mönchengladbach, Germany). The symposium took place in the Reissensburg near Ulm (Germany) which gives the ideal location for such an event.

Age Factors↗
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[Regional hyperthermia with systemic chemotherapy in children and adolescents: feasibility and clinical follow-up of 34 intensively pretreated patients with prognostically unfavorable tumor diseases].

Temperature elevation for a few degrees (degrees C) increases significantly the cytotoxicity of several antineoplastic drugs under experimental conditions. An isolated elevation of the tumour temperature, which is possible since a few years, might be able to improve local tumour control without increasing the systemic toxicity. This study was performed to examine the feasibility of regional hyperthermia with systemic chemotherapy in pediatric patients. The special interests were the level of temperatures that could be achieved as well as the degree of toxicity and undesired side effects. Furthermore there was some hope to attain local tumour control in cases with very poor prognosis. 34 patients up to 18 years were treated in Munich and Essen until the end of 1992. 21 suffered of local relapse, in 11 cases it was the 2nd up to the 7th relapse. In another 11 cases the indication for the combined treatment was tumour progress or non-response to previous therapy. 33 patients were pretreated by aggressive chemotherapy, 20 patients had received radiotherapy before. In 28 cases the tumour was located in the pelvis. The heating device that we use is commercially available. It is based on external electromagnetic radiation which induces heat by absorption within the tissue. Since the temperature distribution inside the tumours is very heterogeneous thermometry is necessary which can only be performed invasively. For this sake we use closed tip catheters which are inserted into the tumour by puncture or surgically. The catheters remain in place for the whole treatment duration of several weeks. Chemotherapy was performed in treatment cycles (3.4/patient) mainly using etoposide, ifosfamide, and carboplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
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[Sonography of the larynx in children. New perspectives due to the use of computerized sonography: 2: Sonographic findings in a case of laryngeal papillomatosis].

On our opinion one important indication for sonographic diagnosis in future are masses in the larynx area: in infancy or childhood mainly laryngeal papillomatosis. In one of our boy patients with massive laryngeal papillomatosis laser surgery was first performed at 15 months of age. After a second and third procedure interferon-therapy was begun. Sonographically it was easily possible to follow the course in control examinations. Sonographic findings correlated well with laryngoscopic findings. Laryngoscopy could therefore be limited to a minimum.

Follow-Up Studies↗
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[Comparison of chemotherapy alone with allogeneic bone marrow transplantation in first full remission in children with acute myeloid leukemia in the AML-BFM-83 and AML-BFM-87 studies--matched pair analysis].

16 patients of studies AML-BFM-83 and -87 with allogeneic bone marrow transplantation (BMT) in first complete remission (CR) were compared with matched controls with postremission chemotherapy (CT-MC). CT-MC were selected from 250 non-grafted patients with a minimum of remission duration corresponding to the median interval between remission and allogeneic BMT (7.3 and 3.6 months in studies BFM-83 and BFM-87). Matched pair criteria according to prognostic significance were: blast cell reduction day 15 in bone marrow, FAB subtypes, white blood cell count, age, and time to CR. Therapy results in BMT and CT-MC groups were comparable: 2 relapses and 2 treatment-related deaths after BMT vs. 5 relapses. The probability for event-free interval of 9 years was: .73 (SD .12) in the BMT group vs. .67 (SD .12) in the CT-MC group. Early and late toxicity was higher in the BMT group. 3 children of the BMT group had tolerable or severe sequelae (convulsive seizures, hemiparesis). Currently, there is no advantage for allogeneic BMT in first CR according to our results. Only high risk patients should be grafted as soon as possible after achieving CR.

Adolescent↗
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[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↗
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[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↗
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[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↗
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[131(I)-meta-iodobenzylguanidine treatment of 32 children with therapy-refractory neuroblastoma].

The selective uptake and accumulation of 131J-Metaiodobenzylguanidine in neuroblastoma cells in vivo may be utilized for targeted irradiation. The experience with 32 neuroblastoma patients refractory to conventional high dose chemotherapy is reported. At diagnosis 8 patients had Evans stage III and 22 stage IV. 11/32 experienced recurrences after complete tumor disappearance and before mIBG treatment, 16/32 progressed from residual or nonresponding tumor and in 3/32 insufficient tumor regression by chemotherapy was observed. 2 children received one mIBG course each with no evidence of disease. Mean applied activity was 128 mCi per course (35-300 mCi), 360 mCi per patient (80-1033 mCi) and 19.2 mCi/kg per patient (3.2-37.9 mCi/kg), respectively. A total of 84 courses was given (mean 2.6 per patient). Pain relief was noticed in 14/14 patients with bone pain. Complete or very good partial remission was achieved in 5/32, partial remission in 11/32 and stable disease in 6/32 patients. In 8 children progression occurred and 2 patients were not evoluable. 20 children died, 12 are still alive (6 patients with initial stage IV, 6 with stage III disease). Main side effect was transient thrombocytopenia, which became more severe with increasing number of courses. We conclude that mIBG treatment is effective in some patients with refractory neuroblastoma and may be utilized in the future as front line therapy for patients achieving only incomplete regressions after high dose chemotherapy.

3-Iodobenzylguanidine↗
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[EICESS 92 (European Intergroup Cooperative Ewing's Sarcoma Study)-- preliminary results].

BACKGROUND: Ewing tumor patients' outcome is 50% to 60% with current treatment strategies. Questions concerning toxicity and secondary malignancies are of increasing importance. PATIENTS AND METHODS: 631 patients were registered with the German EICESS study center of the European Intergroup Cooperative Ewing's Sarcoma Study, 369 patients were randomized. Treatment apart from local therapy consisted of 14 courses of Vincristine, Actinomycin D, Cyclophosphamide or Ifosfamide, Adriamycin (Doxorubicin), with or without Etoposide. First results concerning event-free survival (EFS), toxicity, and the rate of secondary malignancies three years after diagnosis are presented. RESULTS: Three year EFS was 0.66 for patients with localized tumors, 0.43 for patients with primary pulmonary/pleural metastases, and 0.29 for patients with other metastases, respectively. Large tumor volume or pelvic site, especially if inoperable, were adverse prognostic factors. Both histological and MRT-defined response were positively correlated to outcome. Up to 67% of patients experienced WHO grade IV toxicity, mostly related to bone marrow depression. The treatment related mortality was 1% (6/631). Until 15.02.1999, six of 687 patients have suffered secondary malignancies, two of six after (additional) myeloablative therapy. CONCLUSIONS: EICESS 92 treatment is toxic, but manageable and compares favorably to international results. New strategies must be sought for certain risk groups of patients.

Adult↗
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[High-dosage chemotherapy in primary metastasized and relapsed Ewing's sarcoma. (EI)CESS].

BACKGROUND: Patients (pts) with primary metastatic Ewing tumours (ET) have a poor prognosis for event free survival (EFS) compared to pts with localised disease. Following relapse the prognosis is extremely poor. Therefore these primary metastatic and relapsed pts were piloted for high dose therapy (HDT) for the last years. PATIENTS AND METHODS: Between April 1984 and May 1997, 131 ET pts who underwent HDT were registered in the German CESS/EICESS office: 79 pts with primary metastases and 52 pts with relapsed tumours. After induction therapy, consisting of chemotherapy and local therapy, pts received high dose regimens, mainly based on melphalan and/or etoposide (92%). Stem cell rescue was applied from allogeneic bone marrow (n = 13), autologous bone marrow (n = 17), or peripheral blood stem cells (n = 95). The date of analysis was September 1st, 1998. Outcome was calculated by Kaplan-Meier-analyses. RESULTS: The median time under study since high dose therapy was 3.7 years. 35/131 pts (26.7%) were in continuous complete remission, 80/131 pts (61.1%) had relapsed or progressed, 11/131 pts (8.4%) died of complications and 5/131 pts (3.8%) presented with secondary malignancies. For the total group of primary metastatic pts, EFS five years after diagnosis was 19% for pts with HDT and 27% for those without (p = 0.9209). The subgroup of pts with primary lung and bone metastases seemed to benefit from HDT (EFS five years after diagnosis: 34% versus 5%, p = 0.0001). Outcome of pts with an early ET relapse (< 2 years) was also improved by HDT (EFS four years after relapse: 17% versus 2%, p = 0.0001). CONCLUSIONS: The total group of primary metastatic ET pts showed no obvious benefit from HDT, based on melphalan and/or etoposide. Pts with metastases to multiple organ systems, and early relapse seemed to benefit from HDT. The value of HDT should be assessed in prospective clinical trials.

Adolescent↗
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Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience. German/Austrian Pediatric Aplastic Anemia Working Group.

Since the introduction of combined immunosuppressive therapy (IST) into management of aplastic anemia (AA) in childhood response and probability of survival improved. In contrast to bone marrow transplantation (BMT), however, patients after IST are not considered cured as high rates of relapse and development of clonal disease demonstrate. From 11/93 to 9/97 114 children (65 m, 49 f; median age 9.5 y.) from 37 centers in Germany and Austria were registered in the SAA 94 study. 86 patients lacking a matched sibling donor received IST. Most of the patients suffered from very severe (VSAA: PMN < 200/microliter) or severe AA (SAA: PMN < 500/microliter). All patients were treated with combined IST consisting of ALG and Cyclosporin A (CSA). VSAA and SAA patients were additionally treated with G-CSF. Therapy response was evaluated at day 112, after 6, 12 and 18 months. 8/86 patients died, the probability of survival being 87% after 4 years. At d 112 61% of evaluable patients became independent of transfusions (IST response: CR + PR), 13% with normal blood counts (CR). After 6 months 33% showed CR. At 12 and 18 months response improved to 74% resp. 80%, 39% resp. 55% CR. The best response was achieved in the subgroup of VSAA with 90% (PR + CR) and 65% CR after 18 months. 4 patients developed AML 3-19 months after the beginning of IST. In 2/4 pts. an aberrant clone (-7; 5q-) could be detected retrospectively in BM at diagnosis of AA. 3 nonresponders developed chromosomal aberrations (+19; -7, +12; +8) after 4, 12 and 16 months without morphological signs of AML or MDS. Overall 11 relapses occurred at a median time of 12 months (range 5-27 months) after the beginning of IST. 2 of them relapsed under CSA therapy, 2 under tapering of CSA and 7 after cessation of CSA. 7 patients responded again to CSA monotherapy. Overall response rate is 77% with a probability of event free survival (EFS) of 54% after 4 years regarding all complications mentioned as events.

Adolescent↗
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Does megatherapy contribute to survival in metastatic neuroblastoma? A retrospective analysis. German Cooperative Neuroblastoma Study Group.

To evaluate the impact of megatherapy on the outcome of high risk neuroblastoma, 39 patients with stage IV neuroblastoma, who underwent megatherapy, were analyzed retrospectively and compared to 49 patients, who continued chemotherapy according to the German cooperative trial NB85. The groups were comparable concerning age, primary localisation, pattern of metastases, clinical risk groups and response to induction therapy. Overall survival of the megatherapy group was 0.23 +/- 0.07 compared to 0.14 +/- 0.05 of the chemotherapy group (p = 0.0149). In particular patients with partial response to induction chemotherapy appeared to gain from megatherapy, while patients in complete remission did not benefit. Subset analysis confirmed the superiority of megatherapy in patients with bone marrow infiltration at diagnosis, in patients with or without bone metastases at diagnosis and in patients older than 2 years. On the background of the poor prognosis of stage 4 neuroblastoma and lack of other effective treatment modalities these data support the utilization of megatherapy in treatment strategies for stage IV neuroblastoma.

Bone Marrow Transplantation↗
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[Prognosis of children with chronic myeloid leukemia: a retrospective analysis of 75 patients].

UNLABELLED: As the probability of survival of patients with chronic myelocytic leukemia (CML) gradually decreases over a period of 10 years, long-term follow-up is mandatory. Between 1977 and 1994, 68 children and adolescents between 1.0 and 18 years of age with CML in chronic phase and 7 presenting with blast crisis at diagnosis were reported to the study center in Münster. The Philadelphia-chromosome and/or BCR/ABL rearrangement could be detected in 66 children. The 4 Philadelphia-negative patients and 5 patients without karyotyping fulfilled the morphological criteria of CML. Clinical symptoms and hematological findings at presentations were similar to adult patients. THERAPY: Until 1985 chemotherapy consisted predominantly in busulfan (BU), later in hydroxyurea (HU) or a combination of both and since 1987 increasingly in HU plus interferon-alpha. 47 patients (6 in blast crisis) were allografted once or twice (n = 4) (27 HLA-identical, 16 unrelated, 4 haplo-identical) within 2.3-135 months (median 12 months) after diagnosis. RESULTS: 38 of 75 patients (3 in blast crisis at diagnosis) were alive after a median follow-up of 5.5 years. The probability of 12 years survival was 27%, SE 9% for patients in chronic phase. All deaths (n = 19) were leukemia-related in the 27 non-transplanted children. A comparison of survival for patients with or without bone-marrow transplantation (BMT) showed a significant difference in favour of the BMT-group (42%, SE 13% vs. 10%, SE 8%, p log-rank 0.003). The probability of survival increased to 62%, SE 10%, if patients transplanted later than 3 years after diagnosis were excluded. Only few patients (4/39 with information about the cause of death = 10%) died due to recurrent CML after BMT. CONCLUSION: Our data confirm the unfavourable outcome of CML in pediatric patients if treated with chemotherapy alone. With early BMT high cure rates can be achieved. If transplant-related mortality which in our patient group was 21% (8/39) can be reduced, even a higher cure rate appear realistic for the future.

Adolescent↗
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[Treatment of chronic myeloid leukemia in children and adolescents--concept of the multicenter pilot study CML-ped].

CML is a rare malignancy in childhood not yet being treated by an established protocol of the Society of Pediatric Oncology and Hematology (GPOH). Up to now only allogeneic bone marrow transplantation (BMT) offers a curative treatment option. After being enrolled into the study "CML-päd" patients with a matched sibling donor should undergo BMT within six months after diagnosis and within one year if an unrelated donor can be identified. Progress in palliative therapy results from the experience in adult patients: Hydroxyurea in combination with interferon alpha (IFN) is the treatment of choice. One aim of the study is to monitor quantitatively in bone marrow aspirates the activity of the disease in all patients on treatment every three months by performing cytogenetics and molecular analysis. As a pilot protocol intensification of treatment by idarubicine and cytarabine is scheduled one year after diagnosis for those patients not undergoing BMT and exhibiting after IFN treatment less than partial response. After progress to the accelerated phase of the disease a decision has to be made on an individual basis whether the patient should undergo new experimental treatment approaches.

Adolescent↗
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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↗
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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↗
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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↗