PubMed Health⌕ Search

Biomedical subjects

W Siegert

Publications and source records attributed to W Siegert.

At least 109 records · Page 6Linked to original sources
PubMed1994

Molecular characterization of illegitimate TCR delta gene rearrangements in acute myeloid leukaemia.

Recently, we and others have shown the occurrence of TCR delta gene rearrangements in acute myeloid leukaemia (AML). In this study we describe the molecular characteristics of these rearrangements by the polymerase chain reaction (PCR) and the direct sequencing of PCR products. 11 rearrangements were characterized in blast cell samples from six patients. We found a heterogenous pattern of TCR delta gene rearrangements with involvement of V delta 1-5 regions. These findings differ from observations in T-ALL and B-cell precursor ALL, where predominantly usage of V delta 1 and V delta 2 regions has been described. Furthermore, extensive diversity of junctional sites was observed, including addition of up to 37 N nucleotides, nucleotide deletions at junction sites of V delta and J delta segments and usage of up to three D delta segments. The D delta 3 fragment was the most frequently used diversity element and was found in 10 rearrangements. Nine of the 11 rearrangements were non-functional, either incomplete or out of the reading frame. Therefore a functional TCR delta cannot be expressed in these myeloid blast cells.

Adult↗
PubMed1994

Detection of herpesvirus type 6 by polymerase chain reaction in blood donors: random tests and prospective longitudinal studies.

In order to evaluate the prevalence of HHV-6 in blood donors, we examined 112 persons by polymerase chain reaction (PCR) and ELISA. HHV-6 antibodies could be detected in 107/111 (96.4%) of the donors. The median ELISA antibody level was 0.451 (range 0.056-0.914). 14 individuals (12.5%) were PCR positive in either oral lavage fluid, urine or buffy coat. Six persons (5.4%) were PCR positive in buffy coat samples. The prospective longitudinal analysis of 11 donors for periods between 7 and 13 weeks revealed that 4/6 persons who were initially PCR negative had positive tests in 9/63 weeks studied. Two persons were consistently PCR positive over the whole observation period of 12 and 13 weeks. HHV-6 variants could be determined in 14 persons as variant A in nine and variant B in five cases. These observations emphasize the high prevalence of HHV-6 and suggest that some blood donors carry detectable concentrations of the virus and therefore may be a source for transmission of HHV-6. The finding of positive PCR in antibody negative individuals suggests that antibody determination may not be sufficient to identify potentially infectious persons.

Antibodies, Viral↗
PubMed1994

Peripheral T-cell non-Hodgkin's lymphomas of low malignancy: prospective study of 25 patients with pleomorphic small cell lymphoma, lymphoepitheloid cell (Lennert's) lymphoma and T-zone lymphoma. The Kiel Lymphoma Study Group.

Peripheral T-cell lymphomas comprise a heterogenous group of low- and high-grade malignancies differing in their histopathological appearance and also in clinical and prognostic aspects. We prospectively studied 25 patients with low-grade peripheral T-cell lymphomas: pleomorphic, small cell lymphoma (PSC) (n = 9), lymphoepitheloid (Lennert's) lymphoma (LEL) (n = 12) and T-zone lymphoma (TZL) (n = 4). The median patient age was 55 years (range 19-75 years); the male to female ratio was 1.5. 13 patients (52%) had limited stages (I+II), 12 patients (48%) had advanced disease (stage III+IV). 21 patients received the COPBLAM/IMVP-16 regimen. Two patients received more intensive treatments; two received less intensive therapy. Complete remissions were achieved in 16/25 patients (64%). The median observation time of surviving patients was 30 months (range 5-72 months). The actuarial overall survival and event-free survival at 2 years of 21 patients receiving COPBLAM/IMVP-16 were 69% and 35%, respectively. Intensive chemotherapy led to complete remissions in about 60% of the patients and to long-term disease-free survival for one-third. The observed clinical courses illustrate the aggressive nature of PSC, LEL and TZL.

Adult↗
PubMed1994

Microbiologic contamination of peripheral blood stem cell autografts.

We have determined the incidence and clinical significance of positive microbiologic cultures in a series of 290 peripheral blood stem cell concentrates in 95 patients undergoing multiple apheresis procedures for autologous stem cell rescue. Specimens for bacterial cultures were obtained after processing of the autografts just prior to freezing. The incidence of microbial contamination was 4.5% (n = 13). The predominant pathogenic microorganism cultured was coagulase-negative Staphylococcus (n = 11). From 8 patients with contaminated leukapheresis products 6 underwent autologous stem cell transplantation. Five patients received 1-5 culture-positive stem cell concentrates without serious sequelae, whereas the sixth patient was autografted with noncontaminated leukapheresis products, 1 concentrate contaminated with Aspergillus fumigatus being not reinfused. No microorganism present in the stem cell autograft was recovered in vivo in the posttransplantation period, although fever as a sign of infection occurred in all but 1 patient. Peripheral blood stem cell collection and ex vivo processing for cryopreservation may result in microbiologic contamination. However, our data show that infusion of contaminated stem cell autografts does not play a significant role as a source for infections in the clinical setting of autologous stem cell rescue.

Adolescent↗
PubMed1994

High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The German Testicular Cancer Cooperative Study Group.

PURPOSE: This trial evaluated the toxicity and efficacy of high-dose carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in patients with refractory or relapsed germ cell cancer. PATIENTS AND METHODS: Between August 1989 and September 1992, 74 patients with refractory or recurrent germ-cell tumors received one cycle of escalating doses of carboplatin (1,500 to 2,000 mg/m2), etoposide (1,200 to 2,400 mg/m2), and ifosfamide (0 to 10 g/m2). Before high-dose therapy, two cycles of conventional-dose cisplatin, etoposide, and ifosfamide were administered to assess tumor responsiveness. Seventy-four patients were assessable for toxicity and 68 for response. RESULTS: The doses of carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 appeared to be safe. At this dosage, we treated 20 patients and observed World Health Organization (WHO) grade 3 and 4 hematotoxicity (100%), nausea (100%), diarrhea (30%), and hepatotoxicity (10%). All patients developed granulocytopenic fever. At carboplatin doses of 1,500 mg/m2, kidney toxicity was mild, with a median maximum creatinine level of 1.4 mg/dL (range, 1.1 to 3.0 mg/dL). However, at carboplatin doses of 1,750 and 2,000 mg/m2, we observed nonacceptable nephrotoxicity and neurotoxicity. Two (3%) patients died of treatment-related complications. Six patients required hemodialysis, which was temporary in five patients and permanent in one. Objective responses were obtained in 43 of 68 (63%) patients, including 21 (31%) complete remissions (CRs) and 14 (20%) inoperable partial remissions (PRs) with marker normalization. The median observation time of surviving patients was 12 months (range, 2 to 32). The probabilities of overall survival, event-free survival, and the relapse-free survival at 2 years were 44% (SD 8%), 35% (SD 6%), and 67% (SD 9%), respectively. Patients with disease refractory to conventional-dose pretreatment had a poor prognosis, with only one of 23 patients surviving event-free at 7 months after high-dose chemotherapy (HDT). In contrast, 24 of 45 (53.3%) patients with sensitive disease survive event-free with a probability of event-free survival at 2 years of 50% (SD 8%). CONCLUSION: High-dose carboplatin, etoposide, and ifosfamide plus autologous stem-cell transplantation can be used in refractory and relapsed germ cell cancer with acceptable toxicity, and represents an effective, potentially curative salvage treatment.

Adult↗
PubMed1994

Heterogeneity of V delta 2 TCR delta gene rearrangements in acute myeloid leukemia.

In a previous study, we described the occurrence of T-cell receptor (TCR)delta gene rearrangements in 9/100 acute myeloid leukemia (AML) cases. In this study, we further characterized these rearrangements by Southern Blot hybridization using a V delta 2 specific probe and polymerase chain reaction (PCR). Southern Blot analysis revealed that rearrangements involved the V delta 2 gene segment in four patients. Interestingly the restriction fragments detected by the V delta 2 probe differed markedly in size. PCR analysis revealed a complete V delta 2(Dn)J delta 1 gene rearrangement, an incomplete V delta 2D delta 3 rearrangement and a large amplification product, which cannot be explained with normal VDJ recombinatorial processes, in one case each. Furthermore although V delta 2 and J delta were rearranged, no comigration of rearranged fragments was observed and no PCR product was obtained in one case. Obtained results in AML differ from findings in acute lymphoblastic leukemia (ALL) of B-cell lineage, where a more homogeneous pattern of rearrangements has been described. This heterogeneity might be related to the illegitimate occurrence of TCR delta gene rearrangements in AML.

Adult↗
PubMed1994

The role of granulocyte-macrophage colony-stimulating factor in the treatment of germ cell tumors. German Testicular Cancer Study Group.

Hematopoietic growth factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), may gain increasing importance in the treatment of patients with malignant germ cell tumors. For patients with far advanced testicular cancer, who only have a chance of long-term cure in the range of 40% to 50% by standard induction chemotherapy, the German Testicular Cancer Study Group has shown that the application of GM-CSF after PEI chemotherapy has allowed the increase of dose intensity of this three-drug regimen by a factor of 1.4. In 75 evaluable patients an overall survival rate of 79% after a median follow-up of 27 months was achieved. The dose-limiting toxicity of this stepwise dose escalation protocol of the PEI regimen was severe mucositis/enteritis (World Health Organization [WHO] degrees 3/degrees 4) in 33% of the patients and prolonged thrombocytopenia (< 20,000/microL for more than 10 days). In future trials, hematopoietic growth factors will be used in the treatment of far-advanced testicular cancer to generate peripheral blood stem cells (PBSC) that can be used to overcome both granulocytopenia and thrombocytopenia. This approach with the use of PBSC and hematopoietic growth factors will allow us to apply multiple cycles of up-front dose-intensified PEI chemotherapy in this unfavorable subgroup of patients. However, with the establishment of an optimal hematopoietic support in these studies, the value of dose-intensified chemotherapy in advanced testicular cancer will have to be tested against standard dose regimens in prospective randomized trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Successful treatment of chronic graft-versus-host disease with extracorporeal photopheresis.

A 43-year-old woman who had undergone allogeneic bone marrow transplant for chronic myeloid leukemia developed chronic GVHD. Despite cyclosporine A and low-dose glucocorticoids and later concomittent PUVA-therapy, chronic GVHD with severe sclerodermatous manifestations including joint contracture and liver damage progressed. The Karnofsky performance score dropped to under 50%. Extracorporeal photopheresis (ECP) instead of PUVA-therapy was started. To our knowledge, we here report the first case of successful treatment of extensive chronic GVHD with ECP.

Adult↗
PubMed1994

Demonstration of cytomegalovirus after bone marrow transplantation by polymerase chain reaction, virus culture and antigen detection in buffy coat leukocytes.

We prospectively monitored buffy coat leukocytes of 47 patients after 50 marrow transplantations (autologous n = 18, allogeneic n = 32) by polymerase chain reaction (PCR) for the presence of cytomegalovirus (CMV). None of the 18 autologous graft recipients (9 seropositive, 9 seronegative) had positive PCR results or CMV disease throughout the post-transplantation course. Six of 32 allograft recipients (19 seropositive, 13 seronegative) became PCR positive, four of whom developed CMV disease. PCR positive patients were found more often (5 of 10) in the group with acute GVHD grade II-IV compared with 1 of 22 in the group without or with grade I acute GVHD (p = 0.002). Comparison of PCR with antigen assay and virus culture showed an agreement in 90 of 96 (94%) samples. Discordant results were due to a higher sensitivity of the PCR compared with antigen assay (n = 4) and virus culture (n = 6). In conclusion, PCR helps to identify those patients who will not develop CMV disease and narrows down the number of patients who eventually will suffer symptomatic CMV infection. Furthermore, PCR is a useful tool for following the post-transplantation course with respect to CMV and for judging the effect of antiviral treatment.

Adolescent↗
PubMed1994

Low-dose natural interleukin-2 and recombinant interferon-gamma following autologous bone marrow grafts in pediatric patients with high-risk acute leukemia.

Twenty-two patients with high risk hematologic malignancies (13 c-ALL, two B-ALL/NHL, four T-ALL, two AML M2, one pre-pre B-ALL) entered a phase I/II trial with cyclic administration of low dose natural interleukin-2/recombinant interferon-gamma (nIL-2/rIFN-gamma) following autologous bone marrow transplantation (ABMT), in order to induce a cytotoxic antileukemic effect. Eighteen patients subsequently relapsed, corresponding to a Kaplan-Meier estimate of disease-free survival (DFS) of 18%. Compared with a historical group of autologous bone marrow recipients who have not received immunotherapy, there is no significant difference according to DFS. Immunophenotyping of peripheral lymphocytes at the onset and end of therapy cycles revealed the most significant mean increase among the NK cell population (262/microliters +/- 51 vs. 354/microliters +/- 36, p = 0.004). However, even CD3 positive T cells rose significantly (591/microliters vs. 689/microliters, p = 0.04). In vitro NK cell activity tested against the NK sensitive myeloid leukemic cell line K562, and LAK cell activity tested against the LAK sensitive Burkitt lymphoma cell line Raji, was only low. An additional in vitro stimulus with nIL2, however, led to a therapy-dependent increase of cytotoxicity which was significant against Raji cells (25% +/- 4 vs. 41% +/- 5, p = 0.0124) indicating that low dose nIL2/rIFN-gamma enhances precursors of potentially cytotoxic cells in vivo.

Acute Disease↗
PubMed1994

Ondansetron for efficient emesis control during total body irradiation.

Ondansetron is a 5-hydroxytryptamine receptor antagonist which has shown activity in the prevention of emesis following cytotoxic and radiation therapy for cancer. We describe our experience using ondansetron in 25 patients undergoing fractionated total body irradiation (TBI) 12 Gy/3 days as conditioning for bone marrow transplantation. Antiemetic efficiency was investigated during the 3 days of TBI prior to high-dose cytotoxic chemotherapy. Twenty-two of the 25 patients (88%) achieved sufficient emesis control with less than three emetic episodes whereas the remaining 12% experienced three to five emetic events during their worst 24-h period. Eleven patients (44%) had complete control with no vomiting at all. Of 75 'patient days', 52 (69%) were without any emesis, 20 (27%) were associated with one to two and only three (4%) with three to five emetic episodes. Headache occurred in four patients (16%). No other significant adverse effects were seen, in particular no extrapyramidal reactions due to ondansetron. Our data confirm that ondansetron plays a major role in the antiemetic management of patients undergoing TBI.

Adolescent↗
PubMed1994

Ras point mutations occur in acute myeloid leukemia with illegitimate T-cell receptor delta gene rearrangement.

Mutations in the ras proto-oncogenes are the most frequently observed molecular alteration in acute myeloid leukemia (AML). Whether ras mutations occur as late or relatively early events in the multistep process of myeloid transformation, remains an open question. We previously described illegitimate T-cell receptor (TCR)-delta gene rearrangements in a subset of AML. These recombinations were detected in 9 out of 100 de novo AML cases. Southern blot analysis suggested the presence of these recombinations in the vast majority of AML cells and thus could be used as clonal markers. In order to more accurately define the role of ras proto-oncogene mutations in the multistep process of malignant transformation in myeloid leukemias, we performed single strand conformation polymorphism (SSCP) assays, slot blot and direct sequencing analysis on these nine cases with illegitimate TCR delta gene rearrangements. Ras proto-oncogene mutations were found in three of nine cases. Interestingly, SSCP, slot blot and sequencing suggested the presence of the respective mutations in most of the leukemic cells. Thus, ras mutations presumably occurred early in the process of transformation in these three cases.

Adult↗
PubMed1993

Randomized, double-blind, placebo-controlled, phase III study of recombinant human granulocyte-macrophage colony-stimulating factor as adjunct to induction treatment of high-grade malignant non-Hodgkin's lymphomas.

We evaluated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; Sandoz Pharma [Basel, Switzerland]/Schering-Plough [Kenilworth, NJ]) as an adjunct to a modified (mainly cyclophosphamide and doxorubicin increased 1.5-fold) COP-BLAM regimen in the primary treatment of high-grade malignant non-Hodgkin's lymphomas (NHL). Patients (n = 182; stage II-IV; age, 15 to 73 years) were randomized to rhGM-CSF (400 micrograms) or placebo for 7 days subcutaneously after chemotherapy. Efficacy was analyzed for patients receiving at least 70% of study medication (n = 125). The frequency of clinically relevant infection was reduced by rhGM-CSF (28 v 69 infections, 16 v 30 patients, P = .02) with a cumulative probability of remaining infection free in 70% versus 48% (P = .05 log rank test at 190 days). Periods of neutropenia (P = .01 in 5 of 6 courses), days with fever (2.1 v 4.0, P = .04) and days of hospitalization for infection (3.5 v 8.0 days, P = .01) were significantly reduced. Complete response (CR) rates, assessed by prognostic risk, were 15 of 19 (79%) in treated versus 20 of 21 (95%) in controls in the low-risk group (P = .12). In the high-risk group, 31 of 45 (69%) treated patients achieved CR versus 25 of 52 (48%) of controls (P = .04). No difference in survival has been seen after 1 year. Only injection site reactions (45% treated v 7% controls) and rash (26% v 2%) occurred more frequently in treated patients (n = 176). These data show that rhGM-CSF is well tolerated in most patients with NHL, significantly reduces infection, and improves response.

Adolescent↗
PubMed1993

Diffuse pulmonary alveolar hemorrhage after allogeneic bone marrow transplantation.

Diffuse pulmonary alveolar hemorrhage (DAH) is a life-threatening complication following bone marrow transplantation (BMT). So far it has been seen preferentially after autologous BMT. Here, we describe a patient who presented with the picture of DAH after allogeneic BMT. We draw attention to the fact that the syndrome may occur after allogeneic BMT, too.

Adult↗
PubMed1993

A phase I/II study of a stepwise dose-escalated regimen of cisplatin, etoposide and ifosfamide plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with advanced germ cell tumours.

In order to improve the survival of patients with metastatic advanced disease germ cell tumours (according to Indiana University classification), 77 patients were treated by a stepwise dose-escalated combination regimen of platinum (P), etoposide (E) and ifosfamide (I) (PEI) followed by application of granulocyte-macrophage colony-stimulating factor (GM-CSF) (10 micrograms/kg subcutaneously per day at levels 2 and 3) starting the first day after chemotherapy for 10 consecutive days. The maximally tolerated dose was reached at the third dose level with P 30 mg/m2, E 200 mg/m2 and I 1.6 g/m2, all given for 5 days, once every 21 days, for a total of four cycles. Sixty-seven per cent of patients had three or more metastatic sites. Twenty-two per cent of patients had extragonadal primary tumours. 49 (65%) patients achieved complete remission, and 9 additional patients (12%) achieved marker normalisation with unresectable residual disease. After a median follow-up of 27 months, the overall survival is 80%, with 67% of patients remaining free from progression. The dose-limiting toxicities were WHO grades 3/4 mucositis/enteritis in 33% of patients and prolonged thrombocytopenia < 20.000/microliters (> 10 days). Adverse reactions to GM-CSF occurred in 13% of patients. The use of a single haematopoietic growth factor allowed only a moderate increase in dose intensity (factor 1.37). Peripheral blood stem cells will be additionally incorporated into the treatment protocol in order to deliver multiple cycles of an upfront dose-intensified PEI regimen in patients with "poor risk" germ cell tumours with less toxicity.

Antineoplastic Combined Chemotherapy Protocols↗