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Biomedical subjects

W Siegert

Publications and source records attributed to W Siegert.

At least 145 records · Page 8Linked to original sources
PubMed1991

Apparent decrease and elimination of BCR/ABL mRNA-expressing residual cells in patients with chronic myelogenous leukemia after allogeneic bone marrow transplantation.

A modified two-step polymerase chain reaction (PCR) was used for the amplification of BCR/ABL mRNA in 16 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation (BMT). At different intervals after BMT, patient cells were assessed for the presence of BCR/ABL mRNA by two subsequent rounds of PCR amplification; this procedure increased the sensitivity for the detection of one Ph+ cell in 10(4-5) to one cell in 10(5-6). Eight of 16 patients were negative by two-step PCR 1-39 months after BMT, suggesting an elimination of Ph-positive cells or a decrease below the threshold of detection. Although five patients showed negative results by the one-step PCR only, they were tested positive when nested primers were used, indicating a substantial decrease in the amount of BCR/ABL target mRNA compared with earlier pre- or post-transplant analyses. One patient who was still PCR positive 27 months after BMT became negative 12 months later. Persistence of BCR/ABL mRNA-expressing cells correlated with subsequent clinical relapse only when the transplantation was performed during blast crisis. All patients who underwent transplantation in chronic phase, including those with BCR rearrangement by PCR, are in clinical and hematological remission between 24 and 95 months after BMT. We conclude that aggressive chemotherapy combined with total body irradiation is unable to completely eradicate the malignant clone in all CML patients, and it might be speculated that other mechanisms (e.g., graft versus host reaction [GVHD] or graft versus leukemia effect [GVL]) may effectively eliminate residual leukemic cells.

Adolescent↗
PubMed1991

Cisplatin, etoposide, ifosfamide, vincristine and bleomycin combination chemotherapy for far advanced testicular carcinoma.

Forty-eight patients with advanced testicular cancer, defined as abdominal mass greater than 10 cm, mediastinal mass greater than 5 cm, more than 20 lung metastases, or visceral organ involvement were treated with an intensive, alternating five-drug regimen consisting of cisplatin 50 mg/m2 d 1-3, etoposide 170 mg/m2 d 1-3, ifosfamide 5 g/m2 d 15, vincristine 2 mg weekly, bleomycin 15 mg/m2 weekly, q d 28. Thirty-four (71%) of the patients attained tumor-free status. This was achieved by chemotherapy alone in 14 patients and by surgical resection of residual disease in the remaining 20 patients (histology of resected tissue: necrosis 12, mature teratoma 7, viable carcinoma 1). Patients with pure seminoma responded better than patients with nonseminoma (CR 100% vs. 67%, respectively). In a univariate analysis only the value of HCG (less than vs greater than 10,000 U/L) and the number of involved organ sites (less than or equal to 2 vs greater than to 2) had significant influence on the response rate. After a minimum follow-up of 24 months 3 patients (9%) have relapsed. The survival rate is 76% after 36 months, with 61% remaining disease-free. Though this intensive regimen might bestow some of the therapeutic advantages of standard three-drug protocols in far advanced testicular cancer, the results are still less than optimal and warrant the exploration of new therapeutic strategies.

Adolescent↗
PubMed1991

Recombinant human interferon-alpha in the treatment of angioimmunoblastic lymphadenopathy: results in 12 patients.

Peripheral T-cell lymphomas of the angioimmunoblastic lymphadenopathy (AILD) type roughly correspond to lymphogranulomatosis X (LgX). They are currently treated with prednisone, either as a single treatment or with combination chemotherapy. However, both approaches are associated with high risks in this usually elderly patient population (median age 64 years). While looking for therapeutic alternatives to avoid these problems, the efficacy of low dose recombinant interferon-alpha 2a was examined. Patients received 3 x 10(6) IU daily as a subcutaneous (s.c.) injection. Those who achieved a complete remission continued with a maintenance treatment of 3 x 10(6) IU s.c. three times per week. A total of 14 patients received interferon. Twelve were evaluable for response. Six received interferon as primary and six as secondary treatment after the failure of previous treatment with prednisone or chemotherapy. Complete remissions were achieved in four, partial remissions in another four of 12 patients, whereas in the remaining four patients no change or progressive disease was observed. The median remission duration was 3.5 months; the longest durations of complete remissions were 6+ and 7 months. It is concluded that low dose interferon-alpha is an effective and well tolerated drug in T-cell lymphomas of the AILD (LgX) type. It is useful for salvage treatment in patients with contraindications or refractory to combination chemotherapy. It may be useful in adjuvant or maintenance treatment.

Aged↗
PubMed1990

Differential expression of the oncoproteins c-myc and c-myb in human lymphoproliferative disorders.

Altered regulation of oncogene expression has been described in a variety of hematopoietic malignancies. In this study we analyzed the protein level of c-myc and c-myb in 15 established cell lines derived from lymphopoietic disorders and in 45 samples from patients with acute or chronic lymphatic leukemias. Oncoproteins were assayed by radioimmuno-precipitation with polyclonal rabbit antibodies. In B-cell derived lines, such as Burkitt lymphoma and plasmocytoma lines, we found high amounts of c-myc and no or low amounts of c-myb. In contrast, all T-cell-derived lines revealed high levels of c-myb. In addition, T-lymphoma cell lines of low malignancy also exhibited high levels of c-myc, while T-cell lines of high malignancy (acute T-lymphoblastic leukemias) exhibited moderate levels of c-myc. Of the 45 patient samples analyzed, only three (one B-prolymphocytic and two acute T-lymphoblastic leukemias) contained detectable amounts of myc or myb protein. Corresponding to the results found in established cell lines, the B-cell sample revealed a high level of c-myc but no c-myb, while the T-cell samples revealed high levels of c-myb and no or low levels of c-myc. We therefore conclude that the predominance of c-myc or c-myb expression in malignant lymphoproliferative disorders may be associated to the B-cell or T-cell lineage, respectively. Further, regarding the T-cell lines, there is a possible correlation between cell maturation and the level of c-myc found together with a consistently elevated c-myb.

Cell Line↗
PubMed1990

[Stem cell concentrates in autologous transplantation].

For some years, there has been an increasing success in transplanting PBSC instead of autologous bone marrow in patients suffering from leukemic diseases. In healthy cytapheresis donors, we achieved peripheral blood mononuclear cell (PBM) recoveries of 74%, using a discontinuous flow separation technique (Haemonetics V50, Lymphosurge). At the moment, we have collected PBSC from 4 patients (3 AML, 1 ALL) in 28 cytapheresis procedures ranging from 12.9% to 80.1% (mean: 40.1%), whereas stem cell recoveries, defined by CFU-GM, were significantly better (mean: 66%). At present, one of these patients has been transplanted with PBSC alone, receiving 2.11 x 10(8) PBM/kg with 2.8 x 10(4) CFU-GM/kg. His posttransplantation cytopenia was shorter compared to other patients undergoing autologous bone marrow transplantation. The period of disease-free survival is now more than eight months while he is completely reintegrated into social and working life.

Blood Cell Count↗
PubMed1990

[Techniques for bone marrow preparation--a comparison of various systems].

Marrow cell concentration is a fundamental requirement when it becomes necessary to remove red blood cells prior to freezing for autologous or ABH-incompatible allogenous marrow transplantation. We compared 5 different separation techniques and two different cell separators (a: Haemonetics V50 and b: IBM/COBE 2997) routinely used for platelet and granulocyte production.

ABO Blood-Group System↗
PubMed1990

Soluble interleukin 2 receptors in patients after bone marrow transplantation.

An enzyme-linked immunosorbent assay was used to quantify soluble interleukin 2 receptor (IL2R) in the serum of 25 patients prior to allogeneic or autologous bone marrow transplantation and in the early post-transplantation period. A significant correlation between IL2R and the occurrence of fever and/or graft-versus-host disease (GVHD) could be shown. Patients with moderate to severe GVHD (grade II-IV) had significantly higher IL2R levels (median 480 U/ml) than patients without or with acute GVHD grade I (median 139 U/ml). In patients without or with acute GVHD grade I, significant differences in the maximum IL2R levels depended on the duration of fever greater than or equal to 38 degrees C. Evaluation of the peak IL2R levels in patients with fever lasting longer than 6 days led to a median of 260 U/ml and in patients with fever lasting less than 6 days to a median of 118 U/ml. In patients without or with acute GVHD grade I, who developed fever lasting longer than 6 days, IL2R levels started to rise with the onset of fever, reached peak values during temperature maximum and declined parallel with temperature normalization. In patients without or with acute GVHD grade I who developed fever lasting for only 6 days or less IL2R levels remained within the normal range. In patients with acute GVHD grade II-IV, IL2R levels began to rise with the onset of fever, and then continued to rise despite temperature normalization. The peak levels were reached in the early period of acute GVHD. Our observations in BMT patients show that severe infections and acute GVHD are associated with a stimulation of the immune system leading to elevated IL2R serum levels.

Bone Marrow Transplantation↗
PubMed1989

Immunocytochemical detection of p21ras expression in fresh human leukaemic cells and cell lines.

The expression of p21ras proteins was investigated by immunocytochemistry in permanent cell lines and in fresh human leukaemic cells. While high and low levels of p21ras could be detected in most of the cell lines, no significant p21ras immunoreactivity was noted in cells of ten human acute and chronic leukaemias. Thus, notwithstanding its possible role in the initial transformation process in human leukaemias, p21ras expression appears not to be an irrevocable requirement for the maintenance of the transformed state.

Antibodies, Monoclonal↗
PubMed1989

Accidental overdose of mitoxantrone in three patients.

Mitoxantrone is a new effective antineoplastic agent with activity against a wide range of tumors. Compared with the anthracycline drugs doxo- and daunorubicin, it exhibits a clearly lower toxicity and, most importantly, a reduced cardiotoxicity. The analysis of the side-effects recorded after accidental overdosage of the drug gives additional insight into its tolerability. Here we describe our observations in three patients who inadvertently received 100 mg m-2 (two pts) and 183 mg m-2 (one pt) as single slow bolus injections. The main side-effects were moderate nausea and vomiting, shaking chills, and profound but reversible neutro- and thrombocytopenia. There was no immediate cardiac toxicity. One patient with extensive previous daunomycin exposure developed congestive heart failure after 4 months. Two patients were not evaluable for late cardiac complications because of early death due to tumor progression.

Adult↗
PubMed1989

A flow cytometric assay for the determination of cell proliferation with a monoclonal antibody directed against DNA-methyltransferase.

The enzyme DNA-methyltransferase is responsible for the methylation of a newly synthesized DNA-strand. A monoclonal antibody directed against DNA-methyltransferase was used to determine cell proliferation by means of flow cytometry. The reactivity of DNA-methyltransferase antibody was compared with the known proliferation markers transferrin-receptor and Ki67. All three methods showed comparable reactivity with the erythroblastic cell line K562 (86%, 81%, 76% respectively). In a second set of experiments peripheral blood mononuclear cells were stimulated with phytohaemagglutinin; in three experiments, a mean of 63% of the cells reacted with DNA-methyltransferase antibody after 72 h of culture as compared to a mean of 6% in the case of unstimulated control cells. HL60 cells were incubated with DMSO and harvested on day 5 of culture. The results obtained show that in differentiated cells the fraction positive with DNA-methyltransferase antibody decreased to levels below 10%. It is concluded that the technique described is a fast and easy method for the flow cytometric determination of cellular proliferation.

Antibodies, Monoclonal↗
PubMed1989

[Risk-adapted therapy of highly malignant non-Hodgkin's lymphomas with COP-BLAM/IMVP-16: a prospective multicenter study].

In a prospective multicenter therapy trial the remission-inducing potential of the COP-BLAM (5 courses) and the possibly not cross-resistant IMVP-16 (2 courses) regimen for advanced diffuse large cell lymphomas were investigated. Inadequately responding patients were switched early after 2-3 courses to the IMVP-16 protocol. Between January 1986 and August 1988 349 previously untreated patients were recruited who fulfilled the entry criteria: age 15-75 (mean 56 years), stage II-IV. A first restaging after 3 courses of chemotherapy was documented for 280 cases, a second restaging following 7 courses of chemotherapy or a final report was available for 221 patients, 130 of which where in CR (59%). These figures include 29 cases who died already during induction-chemotherapy of progressive disease (n = 17) as well as of therapy-related complications in CR (n = 12). Thirty-three patients were switched early to IMVP-16 due to incomplete response at the first restaging; 13 of those achieved CR by the new regimen (39%), 9 achieved a partial remission which was turned into CR by additional radiotherapy in 5 cases. Dose reductions and interval prolongations were necessary at increasing rates with subsequent chemotherapy courses (20-50% of the cycles). Relapses have occurred in 32 patients so far (14 early, 18 after stop of treatment). The median survival was 24 months (n = 309 patients). These data show that this treatment strategy is effective in a large unselected group of patients of relatively high age. However, patients showing only delayed response with this protocol probably need more aggressive regimens to obtain durable remissions.

Adolescent↗
PubMed1988

[Multicenter prospective risk-adapted study on the therapy of non-Hodgkin's lymphomas of high malignancy. Use of COP-BLAM/IMVP-16 and randomized adjuvant radiotherapy--study concept and preliminary results].

In a multicenter prospective randomized therapeutic trial in advanced (stage II-IV disease, Ann Arbor classification) high-grade malignant non-Hodgkin's lymphomas (NHL, Kiel classification) a sequential combination of the COP-BLAM (5 cycles) and the IMVP-16 (2 cycles) protocols was employed. Response was first determined after 2-3 cycles. In a response-adapted manner the therapy was immediately switched to IMVP-16 if only a partial remission or no response was obtained as evidenced by the first restaging. The aim of the study is the investigation of the efficiency of this concept to induce stable remissions. In an additional randomized trial, involving all patients reaching complete remissions after chemotherapy (second restaging), the prognostic relevance of adjuvant radiotherapy as compared to therapy-free follow-up is evaluated. Eighty percent of the 191 recruited qualified patients have so far become evaluable. Complete clinical remissions were achieved in 76/148 (51%) of the patients up to the first, in 52/85 (61%) of the patients up to the second restaging. Only in a few cases did the expected toxicity of intensive polychemotherapy reach WHO grade 3-4, including nausea and diarrhea, infections, septic complications, myelotoxicity, and stomatitis. Four of the 29 deaths recorded so far occurred in complete remission due to treatment-related complications, whereas 22/29 (76%) died in progression and 3 of unrelated causes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Missing Y chromosome in 2 patients with chronic myelocytic leukemia.

2 cases of chronic myelocytic leukemia (CML) without Y chromosome are reported. One is a 45-year-old man with Philadelphia-positive CML, and the other a 74-year-old patient with Philadelphia-negative CML. Cytogenetic analysis of bone marrow and peripheral blood cultures with and without PHA stimulation was carried out. The Philadelphia-positive patient died after 15 months, whereas in the case of the Philadelphia-negative patient, the survival time of 27 months exceeded the median survival time usually reported for Philadelphia-negative CML patients, thus indicating a prognostic relevance of the missing Y chromosome.

Aged↗