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W Siegert

Publications and source records attributed to W Siegert.

At least 73 records · Page 4Linked to original sources
PubMed1998

Detection of tumor cells in peripheral blood samples from patients with germ cell tumors using immunocytochemical and reverse transcriptase-polymerase chain reaction techniques.

The aim of this study was to establish sensitive techniques for the detection of residual germ cell tumor cells in peripheral blood and progenitor cell harvests. For this purpose, we used immunocytochemical staining for cytokeratin filaments and reverse transcriptase-polymerase chain reaction (RT-PCR) for epidermal growth factor receptor (EGF-R) and germ cell alkaline phosphatase (GCAP). Germ cell tumor lines Tera-1 and Tera-2 were titrated into normal peripheral blood. Immunocytochemical staining allowed detection of one cytokeratin-positive tumor cell in 10(5) cells. RT-PCR for EGF-R revealed one tumor cell in 10 cells for Tera-1 and one tumor cell in 10(3) cells for Tera-2, while RT-PCR for GCAP displayed a sensitivity of one tumor cell in 10(6) cells for Tera-1, one tumor cell in 10(4) cells for Tera-2, and no positivity in normal mononuclear cells (n = 20) and progenitor cell harvests (n = 5). The analysis of peripheral blood and progenitor cell harvests from 20 patients with germ cell tumors revealed tumor cell contamination in three patients using immunocytochemical staining and in seven patients by RT-PCR for GCAP. We conclude that RT-PCR for GCAP appears to be suitable for the sensitive detection of residual germ cell tumor cells in peripheral blood and progenitor cell harvests.

Alkaline Phosphatase↗
PubMed1998

Germ cell tumors: dose-intensive therapy.

Dose intensive chemotherapy in germ cell tumor patients has become a relatively safe procedure after the introduction of growth factors and the availability of autologous stem cells for hematopoietic rescue. Carboplatin and etoposide are the most active drugs available today, and are given in one or two subsequent cycles at dosages between 1000 and 2000 mg/m2 and 1200 and 2400 mg/m2, respectively. The potency of this approach is shown by the induction of long-term disease-free survival in a small proportion of patients with multiply relapsed or far advanced disease, deemed incurable with conventional chemotherapy. This observation indicates that cisplatin refractoriness can be overcome by high-dose carboplatin and etoposide. High-dose treatment (HDT) instituted earlier in the course of the disease, ie, for first-line salvage or even in first-line treatment of poor risk patients is better tolerated and is hoped to lead to superior tumor eradication. The value of HDT needs to be determined in randomized studies, some of which are under way.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Subclassification of diffuse large B-cell lymphomas according to the Kiel classification: distinction of centroblastic and immunoblastic lymphomas is a significant prognostic risk factor.

Among high-grade malignant non-Hodgkin's lymphomas the updated Kiel classification identifies three major B-cell entities: centroblastic (CB), B-immunoblastic (B-IB), and B-large cell anaplastic (Ki-1+) (now termed anaplastic large cell [CD30+], [B-ALC]). The clinical prognostic relevance of this distinction was evaluated in a randomized prospective treatment trial (COP-BLAM/IMVP-16 regimen randomly combined +/- radiotherapy in complete responders) conducted in adult (age 15 to 75) patients with Ann Arbor stage II-IV disease (n = 219) diagnosed by optimal histomorphology (Giemsa staining) and by immunohistochemistry. Overall survival was significantly better in CB lymphoma as compared to B-IB (P = .0002) or B-ALC (P = .046). Relapse-free survival was worse for B-IB (P = .0003) as compared to CB lymphomas. The prognostic differences between CB and B-IB were confirmed by multivariate analyses including the risk factors of the International Index. Overall survival was significantly determined by performance status (P = .0003), serum-LDH (P = .036), and B-IB histology subtype (P = .036). Relapse-free survival was influenced by age (P = .007) and histological subtype (P = .007). Thus, the diagnosis of the CB and B-IB lymphomas by the histological criteria of the Kiel classification was identified as an independent prognostic factor in diffuse large B-cell lymphomas.

Adolescent↗
PubMed1997

Long-term survival of patients with recurrent or refractory germ cell tumors after high dose chemotherapy.

BACKGROUND: The optimal treatment of patients with recurrent or refractory germ cell tumors is still a debated topic. High dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) might be promising for intensification of first or subsequent salvage treatment. However, the long-term results of this approach remain largely unknown. METHODS: Between August 1989 and September 1992, 74 patients with recurrent and/or refractory germ cell tumors were treated in a Phase I/II trial with HDCT consisting of carboplatin (1500-2000 mg/m2), etoposide (1200-2400 mg/m2), and ifosfamide (0-10 g/m2). In September 1995 all patients were reevaluated to determine overall response, late toxicities, and survival. RESULTS: Two patients died from treatment-related toxicity shortly after HDCT, and 47 had recurrence or progression of disease after a median of 3 months (range, 1-44 months). Of these latter patients, three were living continuously disease free at the conclusion of this study after a second HDCT regimen, salvage surgery, or chronic oral etoposide treatment. The results were an overall survival of 38% (95% confidence interval, 27-50%) and a failure free survival of 31% (95% confidence interval, 21-43%) at 5 years. There were no long-term survivors among patients whose disease progressed while they were receiving conventional doses of cisplatin before HDCT. Late toxicities consisted mainly or renal impairment (in 21% of patients), paresthesias (in 29%), and ototoxicity (in 18%). CONCLUSIONS: HDCT can be curative for patients with germ cell tumors who do not become disease free after conventional dose chemotherapy but respond to this treatment.

Adult↗
PubMed1997

[High-dose chemotherapy and reinfusion of hematopoietic stem cells in advanced germ cells tumors with poor prognosis--the position in 1996].

High-dose chemotherapy (HDCT) is a promising treatment for patients with germ cell tumours and a poor prognosis. The selection of patients who may profit from this intervention is challenging for the urologist, as the indication has to be carefully established. Exclusion criteria primarily concern impaired organ functions. Prior to HDCT haematopoietic stem cells are obtained after the administration of conventional-dose chemotherapy plus G- or GM-CSF stimulation. HDCT consists of a combination of carboplatin, etoposide and ifosfamide or cyclophosphamide. After HDCT, haematologic monitoring and maximal supportive care are essential. It is therefore recommended that HDCT only be administered at specialized centres.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Nephrotoxicity after high-dose carboplatin, etoposide and ifosfamide in germ-cell tumors: incidence and implications for hematologic recovery and clinical outcome.

High-dose carboplatin, etoposide and ifosfamide (CEI) is an active chemotherapy regimen (HDCT) in solid tumors and lymphomas. In patients with previous exposure to cisplatin, its nephrotoxicity is dose-limiting. To determine the implications of nephrotoxicity on hematological recovery and clinical outcome, we analyzed 150 consecutive patients with germ cell tumors treated between August 1989 and September 1995 with carboplatin 1500-2000 mg/m2, etoposide 1200-2400 mg/m2, and ifosfamide 0-10 g/m2 followed by either BM or PBPC rescue. Five patients died (3%), three in the context of severe renal toxicity and early multiorgan failure. Overall, acute nephrotoxicity occurred in 43/150 (29%) patients, particularly at doses of carboplatin >1500 mg/m2. Hemodialysis was required in 12/150 (8%) patients, but could be discontinued until discharge in all except two survivors. Nephrotoxicity did not delay hematologic recovery when adjusted for the use of PBPC and hematopoietic growth factors by multivariate analysis, but resulted in higher transfusion requirements, more overall toxicities and a longer hospital stay. There were no differences in the response rates or survival in patients with or without nephrotoxicity. Acute nephrotoxicity is a frequent and clinically relevant complication of CEI in germ cell tumors. The acute side-effects from CEI are reversible in the majority of patients.

Acute Kidney Injury↗
PubMed1997

Herpes simplex infection of the jejunum occurring in the early post-transplantation period.

Reactivation of infections with herpes viruses is a frequent and major cause of morbidity after bone marrow transplantation. In this case report we stress that HSV infections of the colon and small intestine should be considered in the differential diagnosis of diarrhea and intestinal bleeding in the early post-transplantation period. Severe acute GVHD and subsequent intensive immunosuppressive treatment may increase the risk for reactivation of HSV infection particularly in situations in which acyclovir prophylaxis has been omitted.

Adult↗
PubMed1997

High-dose chemotherapy with carboplatin, etoposide and ifosfamide followed by autologous stem cell rescue in patients with relapsed or refractory malignant lymphomas: a phase I/II study.

Patients with relapsed or refractory non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) with recurrences after an anthracyclin-containing regimen only have a chance of cure of below 10% with conventional chemotherapy. In order to improve their prognosis, we started a phase I/II trial using high-dose therapy comprising carboplatin, together with etoposide and ifosfamide (CEI), followed by autologous stem cell rescue (ASCR) as consolidation after salvage treatment. Since September 1990, 40 patients with intensively pretreated advanced NHL (n = 24) or HD (n = 16) received one cycle of high-dose therapy (HDT) consisting of carboplatin 1500 mg/m2, ifosfamide 10 g/m2 and etoposide in escalating doses from 1200 mg/m2 to 2400 mg/m2 followed by ASCR. Thirty-nine patients were assessable for toxicity and response. The following doses appeared to be safe: carboplatin 1500 mg/m2, etoposide 2400 mg/m2 and ifosfamide 10 g/m2. All patients developed grade 3 nausea and grade 3 or 4 mucositis. Granulocytopenic fever occurred in 100% with grade 4 infections in 15%. Mild transient kidney toxicity was noted in 36% and liver toxicity in 20% of patients. One toxic death occurred (2.5%). Objective responses were obtained in 36 of 39 patients (92%) with complete remissions (CR) in 24 patients (61.5%) and partial remissions (PR) in 12 (30.7%). Median observation time for surviving patients was 23.3 months (range 3.4-52.3). The probabilities of overall, event-free and relapse-free survival at 2 years are 62, 39 and 55%, respectively. Patients with primary refractory disease or resistant relapse had a poor prognosis. High-dose carboplatin, etoposide and ifosfamide plus autologous stem cell rescue represents an effective, potentially curative salvage treatment with acceptable toxicities.

Adolescent↗
PubMed1997

Peripheral blood progenitor cell collection during hematopoietic recovery following autologous blood progenitor cell transplantation.

BACKGROUND AND OBJECTIVES: Peripheral blood progenitor cells (PBPC) are increasingly used for autologous transplantation after high-dose radio/chemotherapy in patients suffering from cancer. PBPC are usually collected after mobilization with conventional-dose chemotherapy plus growth factor. However, it is conceivable to perform leukapheresis for the second autograft during recovery of hematopoiesis after the first course of HDCT/ABPCT. MATERIALS AND METHODS: We treated two patients this way. In the first, with germ cell cancer, six 12-liter leukaphereses yielded 1.8 x 10(6) CD34+ cells/kg after mobilization with cis-platinum, etoposide and ifosfamide (PEI) plus granulocyte colony-stimulating factor (G-CSF). The second patient, with relapsed Hodgkin's disease, underwent PBPC collection after treatment with dexamethasone, carmustine, etoposide, cytarabine and melphalan (DexaBEAM) plus G-CSF. Due to excellent mobilization, 8.5 x 10(6) CD34+ cells/kg were collected by one 12-liter leukapheresis. Both patients then underwent PBPC collection during hematopoietic recovery following HDCT and ABPCT. RESULTS: In patient 1, following HDCT and ABPCT, three 12-liter aphereses resulted in 0.7 x 10(6) CD34+ cells/kg. In patient 2, also after HDCT and ABPCT, a second autograft with 3.2 x 10(6) CD34+ cells/kg was harvested by a single 10-liter apheresis. No adverse effects were seen in either patient during apheresis following ABPCT. To our knowledge this is the first report dealing with PBCT collection during hematopoietic recovery following HDCT and ABPCT. CONCLUSIONS: (1) PBPC harvesting is feasible and well tolerated in this setting. (2) In appropriate patients with efficient PBPC mobilization after conventional-dose chemotherapy, a further PBPC autograft can be collected during recovery of hematopoiesis after ABPCT, serving as a rescue for a second course of HDCT.

Adult↗
PubMed1997

Chronic lymphatic leukemias of T and NK cell type.

T cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) and large granular lymphocyte leukemia of T or NK cell type (T-LGL or NK-LGL leukemia) are chronic lymphoproliferative diseases derived from post-thymic immunocompetent lymphoid cells. T-PLL is morphologically characterized by a prominent central nucleolus in a medium-sized cell expressing a mature T cell immunophenotype. Clonal genetic changes involving chromosome 14 and T cell receptor gene rearrangements are characteristics of these diseases. They are usually progressive and there is no efficient treatment available. The classification of some cases presenting with a morphological picture similar to B-CLL, but with immunophenotypic and clinical features resembling T-PLL, as T-CLL is still controversial. The phenotypic profiles and the establishment of clonality are the hallmarks of defining T-LGL leukemia and NK-LGL leukemia. The CD3+/CD57+/CD56- immunophenotype and the clonal rearrangement of the T cell receptor genes characterize T-LGL leukemia, which presents clinically with a rather indolent course of disease, complicated by frequent infections secondary to neutropenia. NK-LGL leukemia cells express CD3-/CD56+/CD57-, but in most cases clonality cannot easily be established. Clinically the patient may either present with constitutional symptoms and suffer a short and aggressive course of disease or may have a more chronic disease similar to T-LGL leukemia. Therefore, it may be reasonable to subdivide NK-LGL proliferation into the more aggressive 'NK-LGL leukemia/lymphoma' and 'chronic NK cell lymphocytosis'.

Antigens, CD↗
PubMed1996

A prospective study of human herpesvirus type 6 detected by polymerase chain reaction after liver transplantation.

Human herpesvirus type 6 (HHV-6) causes roseola infantum (exanthema subitum) upon primary infection in young children. Thereafter it persists lifelong in the organism. Like other herpesviruses, HHV-6 can be reactivated in periods of immunosuppression - e.g., after organ transplantation. In order to study the incidence and the time to reactivation after orthotopic liver transplantation (OLT) we tested buffy coat lysates before and up to 10 weeks after transplantation for the presence of HHV-6 DNA by polymerase chain reaction (PCR). Forty-six patients (male n=27, female n=19) with a median age of 48 years (range 20-66) were studied. Altogether, 30 of 287 (10.5%) buffy coat samples were PCR-positive. Before OLT 2 of 21 (9.5%) patients were positive. This ratio is not different from healthy blood donor controls. After OLT 13 of 46 (23.8%) patients were positive on one or more occasions. However, there was no statistically significant difference before and after OLT. Ten patients were analyzed for HHV-6 variants by restriction enzyme digestion of PCR products. One patient carried variant A and 9 variant B. In conclusion, HHV-6 can be detected in buffy coat cells after OLT. Our observations do not argue in favor of a reactivation.

Adult↗
PubMed1996

Acute myeloid and T-cell acute lymphoblastic leukaemia with aberrant antigen expression exhibit similar TCRdelta gene rearrangements.

TCR delta gene recombination patterns were analysed by Southern blot, polymerase chain reaction and nucleotide sequencing in acute myeloid leukaemias, with coexpression of lymphoid antigens (Ly+ AML, n=10) as well as in early T-cell acute lymphoblastic leukaemias with (My+ T-ALL, n=10) and without coexpression of myeloid antigens (My(-) T-ALL, n=9). These 29 acute leukaemias exhibiting TCR delta gene rearrangements were selected from 66 Ly+ AML, 14 My+ T-ALL and 12 My(-) T-ALL cases. Similar recombination patterns, namely D delta 2J delta1 and V delta 1J delta1 gene rearrangements, were observed in Ly+ AML and My+T-ALL. In contrast to V delta2 D delta3 rearrangements in B-cell precursor ALL, these rearrangements require activation of a T-cell-specific TCR delta enhancer. Comparison of My+ T-ALL and Ly+ AML with My(-) T-ALL exhibited a higher incidence of incomplete D delta 2J delta1 rearrangements in My+ T-ALL and Ly+ AML. Since a D delta 2J delta1 rearrangement is an early event in TCR delta recombination, these leukaemias seem to be arrested at an earlier stage of differentiation. Similar patterns of TCR delta rearrangements in My+ T-ALL and Ly+ AML suggest existence of a common myeloid/T-lymphoid progenitor cell. Although weak or missing expression of terminal deoxynucleotidyl transferase (T delta T) was found in 7/10 Ly+ AML cases, no difference was observed in numbers of N-nucleotides inserted in junctional regions when comparing with 3/10 cases exhibiting TdT expression. Since TdT activity is necessary for N-nucleotide addition, this finding suggests down-regulation of T delta T expression after rearrangement took place in these Ly+ AML cases.

Acute Disease↗
PubMed1996

Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia. Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incidence at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts < 3% prior to transplant (P = n.s.). However, relapse incidence differed significantly in patients with non-T-cell-depleted transplants and high basophil counts (> 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy.

Adolescent↗
PubMed1996

High-dose chemotherapy as salvage treatment in germ cell tumors: a multivariate analysis of prognostic variables.

PURPOSE: To identify prognostic variables for response and survival in male patients with relapsed or refractory germ cell tumors treated with high-dose chemotherapy (HDCT) and hematopoietic progenitor cell support. PATIENTS AND METHODS: Three hundred ten patients treated with HDCT at four centers in the United States and Europe were retrospectively evaluated. Univariate and multivariate analysis of patient, disease, and treatment characteristics were used for comparisons of response rates and failure-free survival (FFS). RESULTS: The actuarial FFS rate was 32% at 1, 30% at 2, and 29% at 3 years. Multivariate analysis identified progressive disease before HDCT, mediastinal nonseminomatous primary tumor, refractory or absolute refractory disease to conventional-dose cisplatin, and human chorionic gonadotropin (HCG) levels greater than 1,000 U/L before HDCT as independent adverse prognostic variables for FFS after HDCT. These variables were used to identify patients with good, intermediate, and poor prognoses. In the good-risk category, the predicted FFS rate at 2 years was 51%, compared with 27% and 5% in the intermediate-risk and poor-risk categories (P < .001). The increased risk for treatment failure was due to both a significantly lower rate of favorable responses and a significantly higher rate of relapses. Within the prognostic categories, the particular HDCT regimen or higher dosages of carboplatin or etoposide did not have a significant influence on treatment outcome. CONCLUSION: Prognostic variables for treatment response after HDCT can be identified. The proposed prognostic model might help to optimize the use of HDCT in germ cell tumors and warrants validation in future trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Impact of preleukapheresis cell counts on collection results and correlation of progenitor-cell dose with engraftment after high-dose chemotherapy in patients with germ cell cancer.

PURPOSE: To identify predictive factors for a good leukapheresis yield and to determine peripheral-blood progenitor cell (PBPC) dose requirements for rapid hematopoietic engraftment. PATIENTS AND METHODS: Seventy-one patients with germ cell cancer (GCC) underwent PBPC harvest for autologous transplantation following high-dose therapy. Aphereses were performed after chemotherapy during granulocyte colony-stimulating factor (G-CSF) administration. RESULTS: A median of two aphereses (range, two to five) resulted in 4.6 x 10(8) mononuclear cells (MNC)/kg, 15.7 x 10(4) colony-stimulating units granulocyte-macrophage (CFU-GM)/kg, and 6.0 x 10(6) CD34+ cells/kg. Peripheral blood MNC count correlated significantly with number of harvested CD34+ cells per kilogram (r = .49; P < .0001) and with CFU-GM count per kilogram (r = .35; P < .002). Circulating CD34+ cells from peripheral blood gave the best correlations to collected CD34+ cells per kilogram (r = .92; P < .0001), as well as to harvested CFU-GM per kilogram (r = .48; P < .0001). A preleukapheresis number of CD34+ cells greater than 4 x 10(4)/mL was highly predictive for a PBPC collection yield that contained more than 2.5 x 10(6) CD34+ cells/kg harvested by a single leukapheresis. After autologous transplantation, 41 patients were assessable for hematopoietic engraftment. They engrafted in a median time of 9 days (range, 7 to 18) to a WBC count greater than 1.0 x 10(9)/L, 10 days (range, 7 to 18) to an absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L, and 11 days (range, 7 to 62) to a platelet (PLT) count greater than 20 x 10(9)/L. Good correlations were seen between reinfused CD34+ cell count and recovery of WBC count, ANC, and PLT count, with r values of .65 (P < .001), .65 (P < .001), and .45 (P < .03), respectively. Patients reinfused with a PBPC dose greater than 2.5 x 10(6) CD34+ cells/kg recovered hematopoiesis in a significantly shorter time than patients who received less than 2.5 x 10(6) CD34+ cells/kg. CONCLUSION: Rapid hematopoietic engraftment can be achieved by a PBPC dose of greater than 2.5 x 10(6) CD34+ cells/kg. When circulating preleukapheresis CD34+ cell counts are greater than 4 x 10(4)/mL, a PBPC autograft that contains more than 2.5 x 10(6) CD34+ cells/kg can be collected by a single leukapheresis.

Adult↗