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W Siegert

Publications and source records attributed to W Siegert.

At least 91 records · Page 5Linked to original sources
PubMed1996

Preliminary results of stem cell mobilization in chronic myeloid leukemia with a moderate intensity chemotherapy regimen and G-CSF or G-CSF plus IL-3.

Mobilization of Philadelphia chromosome (Ph) negative peripheral blood stem cells has been reported subsequent to intensive chemotherapy. We asked whether peripheral blood stem cells can be harvested subsequent to a less toxic chemotherapy regimen. Patients were treated with idarubicin 12 mg/m2 on day 1 and 2 and ara-C 100 mg/m2 days 1-5 and 5 or 10 micrograms/m2 G-CSF. In case of insufficient yield chemotherapy was repeated using IL-3 and G-CSF for mobilization of stem cells. Fourteen patients received 18 cycles of chemotherapy. The majority of patients were in late chronic phase and treated after secondary (interferon-alpha) IFN-alpha resistance. sufficient numbers of peripheral blood stem cells were harvested in 11 out of 14 patients. Although mixed Ph positive/Ph negative leukaphereses were harvested in the majority of patients, in no case were sufficient numbers of purely Ph negative progenitor cells for transplantation obtained. No toxic deaths were observed during the aplasia and the toxicity was acceptable. These preliminary results demonstrate that this procedure can be safely applied in patients with chronic phase CML and allows the harvesting of sufficient numbers of peripheral blood stem cells. The efficacy of this regimen for the mobilization of Ph negative cells should be further explored in patients at an earlier stage of the disease.

Adult↗
PubMed1995

Human herpesvirus type 7 in blood donors: detection by the polymerase chain reaction.

In order to evaluate the prevalence of human herpesvirus type 7 (HHV-7) in adult blood donors oral lavage fluid, buffy coat, and urine samples from 112 persons were examined by the polymerase chain reaction (PCR) at one time point. In addition, 11 donors were studied longitudinally over 11 weeks. When the results of the initial and the longitudinal study were combined HHV-7 DNA was found in samples from 109 of 112 (97.3%) adult blood donors. On the basis of different sensitivity levels of the first and the nested PCR differences were detected in the viral DNA load in the samples. It was found that lavage fluid regularly carried significantly higher DNA concentrations than buffy coat. Out of 112 donors, 102 (91.1%) and 8 (7.1%) were positive in the first, less sensitive PCR in lavage fluid and buffy coat, respectively (P < .0001). After nested PCR, 107 (95.5%) and 74 (66.1%) were positive in lavage fluid and buffy coat, respectively (P < .0001). Urine samples were found positive only sporadically. The longitudinal study showed that the oral lavage fluid of most of the donors consistently carried HHV-7 over up to 53 weeks, whereas buffy coat samples were positive less often. In conclusion, HHV-7 is found frequently in adult blood donors in the oral lavage fluid and buffy coat, which are, therefore, potential sources of HHV-7 transmission.

Adult↗
PubMed1995

Autografting with blood progenitor cells: predictive value of preapheresis blood cell counts on progenitor cell harvest and correlation of the reinfused cell dose with hematopoietic reconstitution.

One hundred and nine patients suffering from various malignancies underwent 285 apheresis procedures for PBPC collection. A median of two leukaphereses (range: 2-5) resulted in median numbers of 4.6 x 10(8) MNC/kg, 14.1 x 10(4) CFU-GM/kg, and 6.0 x 10(6) CD34+ cells/kg. Preleukapheresis peripheral blood CD34+ cells correlated significantly with collected CD34+ cells/kg (r = 0.94; p < 0.0001) and with CFU-GM/kg (r = 0.52; p < 0.0001). A value > 4 x 10(4) CD34+ cells/ml was highly predictive for a collection yield > 2.5 x 10(6) CD34+ cells/kg harvested by a single leukapheresis. Sixty patients were evaluated for hematologic reconstitution and engrafted in a median time of 10 days for WBC > 1.0 x 10(9)/l (range: 7-21 days), 10 days for ANC > 0.5 x 10(9)/l (7-20) and 11 days for PLT > 20 x 10(9)/l (7-62). Reinfused CD34+ cells/kg correlated significantly with hematologic engraftment (r = 0.44-0.52 and p < 0.006-0.001) as well as CFU-GM/kg (r = 0.36-0.44 and p < 0.007-0.001). A progenitor cell dose > 2.5 x 10(6) CD34+ cells/kg or > 8.0 x 10(4) CFU-GM/kg led to a significantly faster recovery for WBC, ANC, and PLT when compared with patients receiving < 2.5 x 10(6) CD34+ cells/kg or < 8.0 x 10(4) CFU-GM/kg. We conclude that rapid hematopoietic engraftment after high-dose therapy and PBPC reinfusion correlates well with a progenitor cell dose > 2.5 x 10(6) CD34+ cells/kg or > 8.0 x 10(4) CFU-GM/kg, and that above a preleukapheresis threshold of 4 x 10(4) CD34+ cells/ml a PBPC autograft containing > 2.5 x 10(6) CD34+ cells/kg can be collected by a single leukapheresis. We suggest that patients recovering from myelosuppression should be monitored for CD34+ cells in serial blood samples to determine the course of circulating hematopoietic progenitor cells. This issue will help to define the optimal time point to start apheresis and to predict a PBPC autograft harvested by a single leukapheresis, which will lead to rapid and stable hematopoietic reconstitution following transplantation.

Adolescent↗
PubMed1995

Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma: prognostic impact of clinical observations and laboratory findings at presentation. The Kiel Lymphoma Study Group.

BACKGROUND: In order to establish the clinico-pathological properties of angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma, we evaluated the type, incidence and prognostic significance of clinical and laboratory symptoms. PATIENTS AND METHODS: Sixty-two consecutive patients diagnosed at the Kiel lymph node registry participated in the study. The median patient age was 64 years (range 21-87 years) and the female to male ratio was 1:1.4. Ninety percent of the patients were in stage III and IV and B-symptoms were observed in 68%. At diagnosis patients presented with skin rash (49%), pruritus (32%), edema (38%), pleural effusion (37%), arthritis (18%) and ascites (23%). Furthermore, they exhibited autoimmune phenomena such as cold agglutinines, circulating immune complexes, a positive Coombs test, smooth muscle antibodies, rheumatoid factors, immune hemolysis, a paraprotein, antinuclear antibodies and cryoglobulins. RESULTS: In univariate analysis, survival was significantly related to age (p=0.032), stage (p=0.037), B symptoms (p=0.007), rash/pruritus (p=0.038), edema (p=0.030), ascites (p=0.013), number of clinical symptoms including B symptoms (p=0.004) and excluding B symptoms (p=0.017), lactate dehydrogenase (p=0.007) and hemoglobin (p=0.020). CONCLUSIONS: AILD type T-cell lymphoma characteristically differs from other non-Hodgkin's lymphomas in its clinical signs and laboratory symptoms.

Adult↗
PubMed1995

TCR delta gene rearrangements in acute myeloid leukemia with T-lymphoid antigen expression.

In this review we present our data concerning T-cell receptor (TCR) delta gene rearrangements in acute myeloid leukemia with coexpression of T-lymphoid features (CD2/CD4/CD7; Ly+ AML). We found a correlation between TCR delta gene rearrangements and coexpression of these T-lymphoid features. Ten of 66 Ly+ AML and only one of 44 AML cases without this coexpression exhibited TCR delta gene rearrangements (p = .028). In contrast, no correlation was observed between terminal deoxynucleotidyl transferase (TdT) expression and the occurrence of TCR delta gene rearrangements in AML. Rearrangements were found in two of 25 AML with and seven of 71 AML cases without TdT expression. Interestingly, nucleotide sequencing of junctional sites revealed up to 36 N-nucleotides in cases without or with only weak TdT expression indicating downregulation of TdT expression after the TCR rearrangement took place. Complete V delta 1J delta 1 and incomplete D delta 2J delta 1 gene rearrangements were observed most frequently in Ly+ AML. These recombination patterns were similar to patterns observed in acute T-lymphoblastic leukemia with coexpression of myeloid features (My+ T-ALL) suggesting transformation of a common myeloid/T-lymphoid progenitor cell in these cases.

Acute Disease↗
PubMed1994

Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis.

We previously reported the cloning, and characterization of a receptor tyrosine kinase, axl, from two patients with chronic myelogenous leukemia. Herein, we describe the expression pattern of axl in normal and malignant hematopoietic tissue axl message is detected in normal human bone marrow but not significantly in normal blood leukocytes. Cell separation experiments showed that axl is expressed in hematopoietic CD34+ progenitor and marrow stromal cells, at low levels in peripheral monocytes, but not in lymphocytes or granulocytes. Consistent with the normal pattern of axl expression, axl RNA was found predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with myeloproliferative disorders (acute myeloid leukemia, chronic myeloid leukemia (CML) in chronic phase, CML in myeloid blast crisis, and myelodysplasia) showed significant axl transcription, as compared with 1 of 45 (2%) lymphoid leukemias (chronic lymphocytic leukemia, acute lymphocytic leukemia, and CML in lymphoid blast crisis). Treatment of K562 cells with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), administration of interferon alpha (IFN alpha) to normal monocytes, and treatment of U937 cells with TPA and IFN tau significantly induced axl expression, supporting a role for this kinase in the intracellular signaling of myeloid cells through a variety of biochemical pathways. These results suggest that the axl kinase may be operative in normal and malignant myeloid biology.

Base Sequence↗
PubMed1994

Herpesvirus type 6 in patients undergoing bone marrow transplantation: serologic features and detection by polymerase chain reaction.

To evaluate the potential role of human herpesvirus type 6 (HHV-6) infection in patients after bone marrow transplantation (BMT) we sequentially analyzed buffy coat leukocytes, oral lavage fluid, and urine from 57 patients for the presence of HHV-6 DNA by polymerase chain reaction (PCR) before and after 60 BMTs. Twenty-four patients undergoing autologous BMT and 36 with allogeneic BMT were studied. Thirty-six patients (60%) were PCR positive in one or more tests. The majority of PCR-positive patients had positive results only sporadically, in 1 (n = 23) or 2 weeks (n = 5). Six patients were positive in 3 to 5 weeks. In 2 patients, we found a high frequency of positive tests, in 7 of 7 and 10 of 10 weeks analyzed. Twenty-four patients (40%) remained PCR negative throughout the post-BMT period. There was a significant correlation between the results of HHV-6 PCR and the occurrence of acute graft-versus-host disease (aGVHD). In grade II-IV, 6 of 8 (75%) patients had 2 or more positive PCR tests, compared with 5 of 25 (20%) patients without or with grade I aGVHD (P = .01). There was no difference in the outcome of PCR tests with respect to the type of BMT or pre-BMT HHV-6 enzyme-linked immunosorbent assay titers. Restriction enzyme analysis of PCR amplificates from 18 patients showed HHV-6 variant B in 16 (88.9%) and variant A in 2 cases (11.1%). We conclude that HHV-6 DNA can be detected in 60% of the patients after BMT. HHV-6 DNA can be detected more frequently in patients with moderate and severe aGVHD than in patients without aGVHD or with mild aGVHD.

Adolescent↗
PubMed1994

High-dose consolidation with local radiation and bone marrow rescue in patients with advanced neuroblastoma.

Twenty-six children with advanced neuroblastoma were consolidated with cisplatin, BCNU, etoposide, melphalan, 21 Gy of local radiotherapy, and bone marrow rescue in a multicenter study. All patients were over 1 year of age at diagnosis. Twenty-two patients were treated in first complete or partial remission and four in second complete or partial remission. Hematologic rescue was autologous (n = 23), allogeneic (n = 2), or syngeneic (n = 1). Extrahematological toxicity involved primarily the gastrointestinal mucosa. Among five fatal toxicities, three included intestinal hemorrhage. Fourteen patients relapsed after BMT, four of them at the primary site. Seven children survive progression-free after 16-56 months. These results are essentially not different from a single-center study with the same protocol or from other published studies. The value of megatherapy for patients with advanced neuroblastoma or for a subgroup of them can only be established on a larger number of patients than most national trials accrue.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Treatment intensification in disseminated germ-cell tumors.

Despite major improvements in the treatment of germ cell tumors the results remain unsatisfactory in patients with "poor risk" initial presentation, with inadequately responding or relapsed disease. The alternating use of noncrossresistant drugs or dose-intensified treatment regimens have not proved to be superior to conventional regimens, although the role of early treatment intensification with the use of hematopoetic growth factors or hematopoetic stem cell reinfusion warrants further investigation. In phase I/II trials patients considered incurable with conventional treatment regimens have been successfully salvaged by high-dose chemotherapy and autologous stem cell reinfusion. Several phase III trials to define the role of this novel approach are planned or ongoing in the USA and Europe.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Detection of allelic loss within the beta 1-interferon gene in childhood acute lymphoblastic leukemia using differential PCR.

Deletion of the short arm of chromosome 9p involving the beta 1-interferon (IFN) gene has been implicated in the process of malignant transformation in lymphomas and acute lymphoblastic leukemias. Since cytogenetic analysis is frequently unsuccessful in clinical samples, we used a recently described differential PCR technique to detect losses within the beta 1-IFN gene in 86 acute leukemias. Using differential PCR, no beta 1-IFN deletion was detected in 44 acute myeloid leukemia (AML) and eight control samples. However, five of 42 acute lymphoblastic leukemia (ALL) probes (12%) exhibited loss of the beta 1-IFN gene (three common ALL, two T-ALL). Cytogenetic analysis was performed independently in three of these five cases and revealed abnormalities of chromosome 9p in two samples. Two of five T-ALL cases exhibited a loss within the beta 1-IFN gene, compared with 3/29 c-ALLs, suggesting a predominance of IFN gene loss in T-ALLs. These data indicate that PCR can be used for rapid detection of gene dosage phenomena in clinical leukemia samples.

Acute Disease↗
PubMed1994

Overexpression of the Raf-1 proto-oncogene in human myeloid leukemia.

The Raf-1 protein, a cytoplasmic serine/threonine kinase, plays an important role in signal transduction pathways. In order to examine the role of Raf-1 in human myeloid leukemia, we determined raf-1 mRNA expression by Northern blot analysis in blast cell samples from 27 acute myeloid leukemia (AML) cases and peripheral blood mononuclear cells from six healthy donors. A normal raf-1 transcript size was detected in all cases investigated. However, overexpression of raf-1 mRNA was found in 2 of 27 AML cases, both of which were erythroleukemias (AML, FAB M6).

Acute Disease↗
PubMed1994

A potential role for human herpesvirus type 6 in nervous system disease.

Human herpesvirus type 6 (HHV-6) is a new representative of the herpesvirus family which was associated with a spectrum of diseases, including myalgic encephalitis, meningitis and the chronic fatigue syndrome. We set out to study the potential role of HHV-6 in multiple sclerosis (MS) (n = 21), facial palsy (FP) (n = 19) and Guillain-Barré-syndrome (GBS) (n = 7). Results were compared with a control group (CG) (n = 16). We analyzed paired samples of serum and cerebrospinal fluid (CSF) with the polymerase chain reaction (PCR) for the presence of HHV-6 DNA. The studies were complemented by ELISA determination of serum antibodies against HHV-6. In the MS group we detected HHV-6 DNA in the CSF from three of 21 (14.3%) patients but not in the corresponding serum samples. In FP, GBS and controls CSF and serum PCRs were negative in all cases. HHV-6 serum antibody titers were significantly higher in MS compared with FP, GBS and controls. These findings suggest that HHV-6 may play a role in MS.

Adolescent↗