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T Klingebiel

Publications and source records attributed to T Klingebiel.

At least 127 records · Page 7Linked to original sources
PubMed1994

[Technical aspects of autologous bone marrow transplantation].

Autologous bone marrow transplantation has become an established procedure in the treatment of malignancies. Especially in patients with hematological malignant diseases, who have no compatible allogeneic bone marrow donor or in patients with solid tumors, in whom the threshold of irreversible bone marrow toxicity is reached by the intensified chemotherapy, this procedure allows the use of a myeloablative therapy. As stem cell sources, bone marrow (BM), peripheral blood-derived stem cells (PBSC), and umbilical cord blood can be used. The risk of contaminating malignant cells in BM or PBSC can be reduced by an in vitro purging of the stem cells. In principle, two different methods exist: one is the negative depletion of contaminating tumor cells and the other is the positive selection of non-malignant hematopoietic pluripotent stem cells. Which of the purging principles will be most effective can only be answered through clinical studies.

Bone Marrow Purging↗
PubMed1994

[Autologous bone marrow transplantation].

Autologous bone marrow transplantation (ABMT) is a treatment modality increasingly used to treat a growing number of malignancies both in children and in adults. The theoretical rationale is the transfer of dose-action relationship from pharmacological theory to clinical practice. The basic principles, the important indications and the problems of this particular approach are discussed. Normally bone marrow from the iliac crest is used as stem cell source, but the possibilities of the approach become broader by using peripheral blood stem cells (PBSC). This treatment modality and its particular use in neuroblastoma is described demonstrating also the results.

Adult↗
PubMed1994

Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: report from the European Group for Bone Marrow Transplantation.

A case control study was performed to investigate the potential advantage of allogeneic bone marrow transplantation in advanced or poorly responding neuroblastoma first remission patients using the European BMT Solid Tumor Registry. Seventeen allogeneic and 34 autologous bone marrow transplantation (BMT) cases were matched based on a number of prognostic factors including age, sex, prior treatment duration, pre-graft response status and bone and BM involvement before BMT. Only single BMT procedures are included. The median age at diagnosis was 47 months (range 18-113 months). The median follow-up time since BMT is 58 months (range 13-133 months). The only significant prognostic factor within the allogeneic BMT (p = 0.012) and autologous BMT groups (p = 0.025) was residual skeletal disease before BMT, detected by mIBG in 86% of the cases. However, the progression-free survival was not significantly different: 35% and 41% at 2 years, respectively. Only half of the allogeneic BMT patients had developed graft-versus-host disease (GVHD): 7 of 9 grade I-II and only 2 of 9 grade IV. The median donor age was very young with 74 months (range 20-240 months) and 10 of 17 were sex matched. Thus absence of GVHD risk factors in young children could be the major obstacle in achieving an anti-tumor effect with allogeneic BMT in neuroblastoma.

Bone Marrow Transplantation↗
PubMed1993

Aneurysmal bone cyst in early childhood. Ultrasound findings.

A 1-year-old child with an aneurysmal bone cyst in the scapula is presented. The sonographic examination showed a cystic formation with intraosseal fluid levels that shifted after repositioning of the child. Similar findings have been reported on CT scans and it is suggested that shifting fluid levels are an indicative feature of aneurysmal bone cyst.

Bone Cysts, Aneurysmal↗
PubMed1993

Impact of megatherapy on survival after relapse from stage 4 neuroblastoma in patients over 1 year of age at diagnosis: a report from the European Group for Bone Marrow Transplantation.

PURPOSE: Relapse from stage 4 neuroblastoma usually carries a poor prognosis. A retrospective study using the European Bone Marrow Transplant (EBMT) Solid Tumor Registry was undertaken to define the role of megatherapy (MGT) in relapsed patients. PATIENTS AND METHODS: After relapse, 33 boys and 15 girls with previous stage 4 neuroblastoma received intensification by MGT followed by either autologous (n = 42) or allogeneic (n = 6) bone marrow rescue in 11 European institutions. The median age at diagnosis was 47 months (range, 14 to 134) and the median interval from diagnosis to relapse was 16 months (range, 4 to 94). Thirty patients had received only conventional-dose primary treatments (group A), whereas 18 patients had previously received intensification with MGT (group B). The median follow-up time of the total group is 95 months (range, 25 to 185). RESULTS: The actuarial overall survival rate at 2 years after MGT for relapse is 27% for group A and 0% for group B (P = .02). Three adverse, independent prognostic factors were confirmed by multivariate analysis using the Cox proportional hazards regression model: an interval of less than 12 months between diagnosis and relapse (P < .0001), nonresponding or untreated relapse (P = .0002), and previous MGT during primary treatments (P = .055). None of the other variables analyzed, such as sex, age, bone or bone marrow involvement at diagnosis or at relapse, and type of MGT at relapse, influenced outcome in this patient cohort. CONCLUSION: Responding patients who relapse more than 12 months from diagnosis who had not received previous MGT appear to benefit from consolidation MGT. Relapse patients who do not fulfill these criteria gain no advantage from this cost-intensive procedure and should be treated differently.

Actuarial Analysis↗
PubMed1992

Case report 756: Chronic multifocal osteomyelitis.

We report the case of a young boy referred to our Department of Nuclear Medicine under the suspicion of a malignant tumor. The leading clinical symptoms were pain in the joints and loss of weight and vitality. Radiographic findings were suggestive of osteogenic sarcoma, but bone scans showed multiple increased tracer depositions along the cortex of femur and tibia, and in the lower and upper jaw. The enrichment pattern was not typical for metastases, but more probably demonstrated the multiple foci of osteomyelitis. This assumption was confirmed by the histological findings, which were diagnosed as primary chronic osteomyelitis. This rare pediatric bone disorder has been described by Giedion et al. The etiology of the disease is unknown, and therapy is discussed controversely in literature.

Child↗
PubMed1992

A phase I study of neuroblastoma with the anti-ganglioside GD2 antibody 14.G2a.

Nine patients with neuroblastoma stage IV were treated with the murine monoclonal antibody 14.G2a, directed against disialoganglioside GD2. The antibody was injected daily for 5-10 days and the total applied dosage ranged between 100 mg/m2 and 400 mg/m2. The peak serum levels of mAb 14.G2a ranged from 28 micrograms/ml to 61 micrograms/ml. Pharmacokinetic data obtained in three patients indicated that the serum elimination of mAb 14.G2a fits a two-compartment model, with an alpha-half-time (t1/2 alpha) between 0.66 h and 1.98 h and a beta-half-time (t1/2 beta) between 30.13 h and 53.33 h. All patients presented with a human anti-(mouse IgG) antibody response either during or shortly after therapy. Eight patients showed a continuous decrease in complement component C4 during therapy, as well as an initial decrease in C3c and an initial increase in C3a, all suggesting an activation of the complement cascade. Side-effects consisted of allergic reactions like pruritus, exanthema, urticaria and of severe pain, predominantly located in the abdomen and lower extremities, which required the use of continuous intravenous morphine. Four patients additionally developed a transient hypertension and one patient experienced a transient nephrotic syndrome. Three patients were treated in an adjuvant setting and are not evaluable for tumor response. Of the remaining six patients, two had a complete remission, two showed a partial remission, and two patients did not respond to treatment.

Antibodies, Anti-Idiotypic↗
PubMed1992

Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase pi gene expression in primary and relapsed state adult and childhood leukaemias.

In a variety of adult and childhood leukaemia cell samples collected at different states of the disease, we analysed in a series of sequentially performed slot-blot or Northern-blot hybridisation experiments the expression of genes possibly involved in multiple drug resistance (MDR) (mdr1/P-glycoprotein, DNA topoisomerase II, glutathione-S-transferase pi), and the expression of the DNA topoisomerase I and histone 3.1 genes. Occasionally, P-glycoprotein gene expression was additionally examined by indirect immunocytofluorescence using the monoclonal antibody C219. No significant difference in mdr1/P-glycoprotein mRNA levels between primary and relapsed state acute lymphocytic leukaemias (ALL) was seen on average. Second or third relapses, however, showed a distinct tendency to an elevated expression of this multidrug transporter gene (up to 10-fold) in part well beyond the value seen in the moderately cross-resistant T-lymphoblastoid CCRF-CEM subline CCRF VCR 100. Increased mdr1/P-glycoprotein mRNA levels were also found in relapsed state acute myelogenous leukaemias (AML), and in chronic lymphocytic leukaemias (CLL) treated with chlorambucil and/or prednisone for several years. Topoisomerase I and topoisomerase II mRNA levels were found to be very variable. Whereas in all but one case of CLL topoisomerase II mRNA was not detected by slot-blot hybridizations, strong topoisomerase I and topoisomerase II gene expression levels, frequently exceeding the levels monitored in the CCRF-CEM cell line, were seen in many cell samples of acute leukaemia. If topoisomerase II mRNA was undetectable, expression of topoisomerase I was clearly visible throughout. These observations might be valuable considering the possible treatment with specific topoisomerase I or topoisomerase II inhibitors. Significant positive correlations were found (i) for topoisomerase I and histone 3.1 gene expression levels in general (P less than 0.001), and (ii) in the CLL samples additionally for the expression levels of the mdr1 gene, and the histone 3.1, topoisomerase I, and glutathione-S-transferase pi genes, respectively.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

[Follow-up evaluation of metastatic neuroblastoma using high dose [131I-meta]iodobenzylguanidine].

Between 1989 and 1990 nine children with neuroblastoma stage IV (according to Evans) have been treated with high-dose [131I-meta]Iodobenzylguanidine (HD-mIBG). The total HD-mIBG dose administered to each child was at mean 699.3 +/- 111 MBq/kg body weight. Prior to (median 28 days) and after (median 50 days) HD-mIBG treatment a diagnostic scan with [123I-meta]Iodobenzylguanidine ([123I-m]IBG) was performed. Scans performed with HD-mIBG were superior to diagnostic scans for the detection of bone lesions in 8/9 children, for the detection of soft tissue lesions in 4/9 children, and for a more precise diagnosis of the primary tumor in 1 child. In 4 children lesions which were primarily identified in the therapeutic scan could be further observed in posttherapeutical examinations.

3-Iodobenzylguanidine↗
PubMed1992

[Juvenile chronic leukemia and chronic myelomonocytic leukemia. Experiences with bone marrow transplantation in childhood in 5 cases].

Chronic leukemias of early childhood (JCML/CMML) are rare malignant diseases for which effective regimens of chemotherapy have not been established. However, some of these patients may be cured by BMT. We report on 4 children with JCML and one child with CMML undergoing BMT from HLA-identical siblings and from matched unrelated donors. 3 of 5 patients are disease-free 9 to 37 months post BMT. According to our observations an effective reduction of blastic cells before BMT seems to be necessary for a sustained remission of these diseases. This reduction can be reached by intensive chemotherapy and by splenectomy before BMT. Moreover, we stress the need for total body irradiation (TBI) during BMT in order to eradicate residual malignant cells.

Blood Cell Count↗
PubMed1991

Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM- and CoALL-protocols: results of the German Cooperative Study.

Fifty-one children between 26 and 214 months of age (median, 100 months) with acute lymphoblastic leukemia (ALL) were grafted in second remission from HLA-identical sibling donors (except for two patients who were grafted with a marrow with 1 antigen-mismatch). Initial treatment and relapse therapy were similar in all patients according to the BFM- and CoALL-protocols (front line: 38 patients according to BFM-protocols and 13 patients according to CoALL-protocols; relapse: 12 patients in study ALL-REZ-BFM 83, 17 in ALL-REZ-BFM 85, 20 in ALL-REZ-BFM 87, and two in ALL-REZ-BFM 90). The conditioning regimens were different, consisting of cyclophosphamide (CY) total body irradiation (TBI) plus (n = 27), VP-16-TBI (n = 23), and CY-TBI and ARA-C (n = 1). Three patients had a second graft after conditioning with CY-TBI for the first transplantation. The second ablative regimen consisted of CY plus VP-16 in the first patient and CY plus busulfan in the two other patients, one of whom relapsed again. All patients but three had bone marrow (BM), either isolated or combined, relapses. Twenty-nine of the patients are in continuous complete remission (CCR), ranging from 1 to 67 months after transplantation with a median time of 30 months. One patient was lost to follow-up in continuous remission. Nine patients died from treatment-related complications (infections and graft-versus-host disease) and 12 patients suffered a leukemic relapse; three of them received a second graft and two are in CCR. Kaplan-Meier analysis yields an event-free survival (EFS) of 0.52 +/- 0.08. The probability of a 7-year relapse-free interval (RFI) is 0.68 +/- 0.08. EFS for patients with late relapses is 0.47 +/- 0.12 and for patients with early relapses 0.56 +/- 0.1. The RFI for patients with late relapses is 0.65 +/- 0.12 and for patients with early relapses 0.69 +/- 0.11. There is a nonsignificant trend towards superior results for patients grafted after conditioning with VP-16 plus TBI. When all patients who are not in CCR at day +125 (which is the median interval between relapse diagnosis and BM transplantation [BMT]) are excluded from the chemotherapy results, there is no significant difference between the results of BMT and chemotherapy for late relapses. On the other hand, there is a significant advantage between chemotherapy and BMT for early relapses over chemotherapy (P less than or equal to .01).

Adolescent↗
PubMed1991

Metaiodobenzylguanidine (mIBG) in treatment of 47 patients with neuroblastoma: results of the German Neuroblastoma Trial.

From 1984 to 1989, 47 children with relapsed, refractory, and/or metastasized neuroblastoma were treated with 131I-metaiodobenzylguanidine (mIBG) in several different treatment combinations. At initial diagnosis, 36 children had Evans stage IV and 11 stage III disease. In 16 of the 47 children, tumor recurred after complete remission prior to mIBG treatment, 26 of 47 progressed from residual or nonresponding tumor, and in 5 of 47 tumor progression during chemotherapy was observed. Altogether the children were treated with a total of 112 courses (range 1-6) with a mean dosage of 8.9 +/- 6.7 mCi/kg body weight/treatment course. Total dose was 283.2 +/- 203.7 mCi for stage III and 388.9 +/- 218.6 mCi for stage IV. Nine of 47 children reached a complete or a very good partial remission (CR and VGPR) from mIBG treatment alone, 13 of 47 achieved partial remission (PR). In an early analysis, 10 patients treated with mIBG in the neuroblastoma trial NB 85 of the German Society of Pediatric Oncology showed no significant difference in survival time compared with 30 conventionally treated children. However, the recent therapy series has been done with higher doses of mIBG, and during improved therapeutic scanning many more bone lesions could be detected than during earlier diagnostic scanning. We conclude that mIBG treatment has not yet fulfilled the expectations for it but still seems for certain indications to be a promising tool to treat neuroblastoma in the future. Moreover, the frontier of neuroblastoma detection is still advancing.

3-Iodobenzylguanidine↗