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Biomedical subjects

W Zeller

Publications and source records attributed to W Zeller.

At least 55 records · Page 3Linked to original sources
PubMed1995

Isodicentric (X)(q13) in haematological malignancies: presentation of five new cases, application of fluorescence in situ hybridization (FISH) and review of the literature.

Idic(X)(q13) represents a rare but recurrent chromosomal abnormality in haematological malignancies. We present five new cases characterized by this particular aberration and review the literature on this subject. The patients were elderly females with a diagnosis of refractory anaemia (1/5), refractory anaemia with ringed sideroblasts (2/5), chronic myelomonocytic leukaemia (1/5), and Philadelphia chromosome-negative chronic myeloid leukaemia (1/5). Three out of the five patients demonstrated an increased proportion of bone marrow ringed sideroblasts. After a follow-up period of 30-57 months all patients but one are alive. Idic(X)(q13) always occurred as the sole chromosomal abnormality, either in one or in two copies. We confirmed the dicentric nature of the aberration by fluorescence in situ hybridization (FISH) on metaphases as well as interphase nuclei using an X-chromosome-specific alpha-satellite probe, and performed chromosome painting to visualize possible additional chromosomal changes involving the X chromosomes. Our findings and the data of 17 previously published cases indicate that idic(X)(q13): (1) may play a significant pathogenetic role in haematological malignancies affecting exclusively females and deriving predominantly from early progenitor cells; (2) is frequently associated with a pathological iron accumulation; (3) indicates a variable prognosis.

Aged↗
PubMed1995

Separation and characterization of mobilized and unmobilized peripheral blood progenitor cells by counterflow centrifugal elutriation.

Peripheral blood stem cell (PBSC) harvests are highly contaminated with lymphocytes. In allogeneic transplantations with PBSC, this might lead to an increased risk of graft-vs.-host disease (GVHD). Marrow graft T cells depletion (TCD) by counterflow centrifugal elutriation (CCE) has been performed to decrease the incidence of GVHD, but in some cases, it has also led to a reduction in the PBSC content of the graft due to the distinct elutriation properties of these cells. We studied the ability of CCE to deplete lymphocytes from recombinant human granulocyte colony-stimulating factor (rhG-CSF)-mobilized PB mononuclear cells (PBMNC) and from unmobilized PBMNC from healthy volunteers. We characterized the elutriation properties of circulating mobilized and unmobilized hematopoietic progenitors. With an experimental three-flow rate CCE procedure, originally described for separation of bone marrow, fractions 24, 28, and Rotor Off (RO) were obtained without impairing yield or viability. This CCE procedure can also be used for the separation of PBMNC harvests by reducing the T cell contamination to or below the range seen in bone marrow grafts; CD3+ cell contamination in the RO fractions of mobilized and unmobilized PBMNC was reduced to < 10% of the input. This could bring allogeneic PBSCT within the range of feasibility. In unmobilized PBMNC, 25% of the recovered CD34+ cells were found in fraction 24, where no colonies were detected, and 50% of the recovered CD34+ cells were found in fraction RO, where most of the colonies were detected. In mobilized PBMNC, 80% of the recovered CD34+ cells were found in fraction RO, together with 90% of the colonies, but almost no colonies or CD34+ cells were detected in fraction 24. CD34+ cells in fraction 24 expressed less CD13, and antigen found on more mature myeloid cells. Mobilization with rhG-CSF causes a shift of CD34+ cells from smaller cells (fraction 24) to larger cells (fractions 28 and RO).

Antigens, CD↗
PubMed1995

Use of cryopreserved bone marrow in allogeneic bone marrow transplantation.

Use of cryopreserved donor bone marrow may facilitate scheduling of allogeneic bone marrow transplantation (BMT) by affording independence of a fixed time for bone marrow donation. The potential risk of damage to hematopoietic stem cells by cryopreservation resulting in delayed engraftment or graft failure has to be taken into account, however. To address these issues, the outcome of 19 matched related BMT (1992-94) performed with cryopreserved donor bone marrow was analyzed and compared with 19 related BMT (1990-93) receiving fresh donor bone marrow (control group). Time to engraftment of patients receiving cryopreserved bone marrow was not different from the control group (ANC > 0.2 x 10(9)/l 15.5 +/- 3.8 days vs 15.8 +/- 5.0 days; ANC > 0.5 x 10(9)/l 17.3 +/- 4.1 days vs 17.9 +/- 5.0 days, respectively). We did not find the previously described trend toward a lower incidence of acute GVHD in patients receiving cryopreserved bone marrow compared with patients receiving fresh bone marrow (acute GVHD > or = II 78 vs 64%). Furthermore, the two groups did not differ in the incidence of chronic GVHD (55 vs 38%) or day 100 survival (74 vs 68%). We conclude that in allogeneic BMT cryopreserved bone marrow cells can be safely used without jeopardising or prolonging time to engraftment.

Adolescent↗
PubMed1995

Deteriorating free radical-trapping capacity and antioxidant status in plasma during bone marrow transplantation.

Organ toxicity in BMT may in part be due to free radical damage. Therefore the 'Total Radical-trapping Antioxidant Parameter of plasma' (TRAP), individual plasma antioxidants, serum iron and linoleic acid, a main substrate of lipid peroxidation, were monitored before and after BMT, and they were compared with values obtained from healthy controls. Seven patients (3 AML, 3 CML, 1 multiple myeloma) receiving 16 mg/kg busulfan, 30-45 mg VP-16 and 120 mg/kg cyclophosphamide were investigated. TRAP values declined during chemotherapy by about 40% (day -9: 1019 +/- 245 mumol/l, mean +/- s.d.; day 0: 660 +/- 164 mumol/l; P < 0.05). The concentration of uric acid, one of the main antioxidants in plasma, decreased markedly (day -9: 339 +/- 108 mumol/l, day 0: 148 +/- 61 mumol/l; P < 0.05) and paralleled TRAP values. Vitamin E and bilirubin did not change from day -9 to 0 whereas vitamin C increased (day -9: 46 +/- 16 mumol/l, day 0: 89 +/- 44 mumol/l; P < 0.05). Serum iron rapidly increased within the pre-transplantation period, reaching values normally seen only in iron overload (day -9: 11.8 +/- 5.2 mumol/l, day 0: 40.6 +/- 6.5 mumol/l; P < 0.05). Linoleic acid levels were normal at the start and decreased substantially (27.0 +/- 1.6 wt% at day -9; 15.7 +/- 4.9 wt% at day 0; P < 0.05), indicating possible lipid peroxidation during high-dose chemotherapy. In conclusion, complex monitoring of the antioxidant status before and after BMT revealed a breakdown of plasma antioxidant defence and of radical-vulnerable lipids, which was associated with high circulating levels of iron.

Adult↗
PubMed1995

Increasing the yield of harvested bone marrow cells by raising room temperature during marrow collection.

The time it takes to harvest bone marrow before transplantation could be reduced significantly by increasing the temperature of the operating room by 8-10 degrees C, to about 28-30 degrees C. In healthy donors, the collected volume of marrow was increased from 22.45 to 36.31 mL/min; in patients who received chemotherapy previously, from 21.67 to 29.98 mL/min. The time to collect a volume of 1200 mL marrow could be reduced significantly, from 57.78 to 38.25 minutes in healthy donors and from 71.07 to 43.36 minutes in patients who received chemotherapy previously, without any loss of quality of the sampled marrow. Operation time and thereby time of anesthesia could be reduced significantly by heating the operating room to a temperature of 28-30 degrees C. Harvesting at higher room temperature did not result in any adverse side effects for the patients. The procedure to increase the body temperature could be simplified by using electric blankets and aluminum foils for wrapping to avoid heat emission.

Adolescent↗
PubMed1995

Transplantation of allogeneic rhG-CSF mobilized peripheral CD34+ cells from an HLA-identical unrelated donor.

We describe the case of a 41-year-old female who underwent allogeneic blood cell transplantation with CD34(+)-enriched cells from an HLA-matched unrelated donor for AML in second CR. The conditioning regimen consisted of TBI (12 Gy), VP16 (1800 mg), cyclophosphamide (7200 mg), and ATG (7200 mg). GVHD prophylaxis consisted of CsA and a short course of MTX. Receiving G-CSF from day +1, engraftment occurred on day +19 after stem cell infusion. Starting on day +10, GVHD grade II (skin and liver) developed that responded to high-dose steroid therapy. The patient died on day +38 due to suspected cerebral aspergillus infection. This case demonstrates the feasibility of primary transplantation of CD34(+)-enriched allogeneic peripheral stem cells from a matched unrelated donor leading to engraftment of donor cells.

Adult↗
PubMed1994

Randomised comparison of CHOEP versus alternating hCHOP/IVEP for high-grade non-Hodgkin's lymphomas: treatment results and prognostic factor analysis in a multi-centre trial.

BACKGROUND: With CHOP, the standard protocol of recent decades, about 30% of long-term survival has been reported. A number of studies using more aggressive multidrug regimens or alternating chemotherapies have recently suggested higher CR rates and increased survival. In 1989 we reported similar results with a combined-modality treatment administering 6 cycles of CHOP supplemented with etoposide and an involved field irradiation for patients in PR or CR. PATIENTS AND METHODS: To confirm the efficacy of this approach, we initiated a prospective randomised trial comparing 4 cycles of CHOP-VP16 (CHOEP) with 4 cycles of two alternating regimens, 'hCHOP and IVEP'. One hundred seventy-five patients with high-grade non-Hodgkin's lymphomas stages II-IV were stratified for age, stage and LDH and randomised to receive either four cycles of cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone (CHOEP) in arm A or four cycles of chemotherapy with a dose-intensified CHOP (hCHOP) alternating with ifosfamide, etoposide, vindesine, prednisolone (IVEP) in arm B. After four cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission. RESULTS: Of the 185 randomised patients, 175 were eligible and 171 evaluable for response and survival. One hundred forty-six of the 171 patients (85%) achieved complete remission (CR) with 87% and 84% CRs in arms A and B, respectively. With a median follow-up of 36 months the estimated overall survival at 2 years is 66% and 73% for arms A and B, respectively. The percentage of all patients in first CR is estimated to be 59% and 55% at 2 years for arms A and B, respectively. None of the differences in CR rate, survival, or relapse-free survival are statistically significant. Multivariate analysis of subgroups incorporating the factors of sex, age, performance status, stage, B symptoms, bulky disease, LDH and histology revealed that only stage and LDH were factors which independently affected outcome. The estimated 2-year survival rate of patients with stages II, III and IV is predicted to be 84%, 62% and 52%, respectively. Patients with LDH > 250 U/l have an estimated survival of 52% at 2 years versus 84% for patients with LDH < or = 250 U/l. According to the newly proposed international score system, the 2-year survival was 81% for low-risk-, 64% for low intermediate risk-, 50% for high intermediate risk-, and 43% for high-risk patients. The toxicity in both arms was tolerable. Three patients died of treatment-related causes (2 in arm A, 1 in arm B). The main toxicity was haematological with 75% of patients suffering from grades 3 or 4 neutropenia at some point during treatment. CONCLUSIONS: We observed no superior benefit for alternating regimens, and conclude that both are effective treatment protocols for aggressive histologic-type malignant lymphomas. The results obtained with four cycles of poly-chemotherapy followed by an involved field irradiation are comparable to programs using more aggressive and/or prolonged chemotherapy.

Adolescent↗
PubMed1993

Immunophenotype of mitotic cells with clonal chromosome abnormalities demonstrating multilineage involvement in acute myeloid leukemia.

Eleven patients with acute myeloid leukemia (AML) were studied with a technique that simultaneously identifies cytogenetic abnormality and immunophenotype of the same mitotic cell. To determine the cell lineages with abnormal karyotypes, monoclonal antibodies in the alkaline phosphatase-antialkaline phosphatase (APAAP) detection procedure were used. The granulocytic/monocytic lineage was involved in the leukemic process in all 11 patients. In nine patients, we also detected abnormal karyotypes in the erythrocytic and/or megakaryocytic lineages. All four patients with secondary AML showed involvement of the granulocytic/monocytic, erythrocytic, and megakaryocytic lineages into the leukemic process, as compared with five of seven patients with de novo AML. One patient with trisomy 8 showed erythrocytic participation in the leukemic process, but in another the erythrocytic lineage had only normal karyotypes. Thus, in AML, the chromosome abnormalities apparently usually originate at the multipotent progenitor cell stage, since in addition to granulocytic/monocytic lineages, erythrocytic and/or megakaryocytic lineages were also involved. Some patients show involvement of granulocytic/monocytic lineages only, however, suggesting that the target cell belongs to a more mature committed progenitor cell stage.

Adult↗
PubMed1993

Monoclonal gammopathy of unknown significance in a bone marrow donor.

We report on a patient suffering from multiple myeloma, for whom allogeneic bone marrow transplantation was planned. Donor workup revealed monoclonal gammopathy of unknown significance. We discuss this finding and stress the importance of performing complete donor examinations.

Adult↗
PubMed1993

P-glycoprotein expression in normal and reactive bone marrows.

The expression of mdr1 gene product P-glycoprotein (P-gp) was investigated in 53 normal and reactive bone marrows by means of immunocytochemistry, using the monoclonal antibody (mAb) C219 and the alkaline phosphatase anti-alkaline phosphatase method. In a limited number of patients, data were confirmed by using the mAb MRK16 or a polymerase chain reaction assay for mdr1 gene expression. There was no history of prior chemotherapy or any malignancy in this group. Bone marrow aspirates were obtained as part of a routine diagnostic programme in bone marrow donors or in patients presenting with a variety of diagnoses such as unexplained gammopathy, fever, anaemia, other changes in peripheral blood smear, rheumatoid arthritis, vasculitis, or urticaria pigmentosa. Morphologically the bone marrow was normal in 23 patients, a megaloblastic erythropoiesis was seen in two patients and unspecific changes were seen in 28 patients. Twenty-seven of 53 samples were found to be positive for P-gp expression with the percentage of positive cells ranging from 2%-80% (mean = 24%). With a cutoff point of 10%, five of 23 normal (22%) and 13 of 28 reactive bone marrows (46%) were considered positive for P-gp expression. There was no obvious correlation between diagnosis or age and P-gp expression. Additional staining for the early surface marker CD-34 was performed in 12 samples, with none of them revealing more than 1% positivity. Since P-gp expression has so far been described only in CD-34 positive bone marrow cells, data suggest that P-gp expression may be reinduced in CD-34 negative cells under conditions which remain to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Intravenous pentoxifylline failed to prevent transplant-related toxicities in allogeneic bone marrow transplant recipients.

Based on encouraging results of a recently published study on the clinical usefulness of oral pentoxifylline (PTX) to reduce transplant-related toxicities, prophylactic pentoxifylline was administered to 31 consecutive allogeneic BMT recipients with hematological malignancies. Patients received PTX as a continuous infusion at increasing dose levels (0.50, 0.75, 1.00 and 1.25 mg/kg/h) starting 1 day prior to the conditioning regimen. At all dose levels, PTX was well tolerated with no significant side-effects. When compared with a historical control group of 61 consecutively transplanted allogeneic BMT recipients, PTX patients did not appear to experience less gastrointestinal (moderate and severe mucositis: 100% vs 68%, p < 0.001), hepatic (hyperbilirubinemia > 1.5 mg/dl: 84% vs 30%, p < 0.001) or renal (creatinine > 1.5 mg/dl: 16% vs 27%, NS) toxicity or to have a lower incidence of GVHD > or = grade III (21% vs 22%, NS). Using i.v. PTX, we were unable to reproduce the reduction in morbidity and mortality in patients undergoing BMT which has been described for prophylactic oral PTX.

Adolescent↗
PubMed1992

Sensitive and species-specific detection of Erwinia amylovora by polymerase chain reaction analysis.

Detection and identification of the fire blight pathogen, Erwinia amylovora, can be accurately done by polymerase chain reaction (PCR) analysis in less than 6 h. Two oligomers derived from a 29-kb plasmid which is common to all strains of E. amylovora were used to amplify a 0.9-kb fragment of the plasmid. By separation of the PCR products on agarose gel, this fragment wa specifically detected when E. amylovora DNA was present in the amplification assay. It was not found when DNA from other plant-pathogenic bacteria was used for the assay. A visible band specific to the 0.9-kb fragment was produced with DNA from fewer than 100 E. amylovora cells. A signal of similar strength was also obtained from E. amylovora cell lysates in the presence of the mild detergent Tween 20. Signals were weaker when bacteria were added to the PCR mixture without the detergent. As with results obtained from hybridization experiments using pEA29 DNA< the PCR signal was obtained with E. amylovora isolates from various geographic regions. This technique could also be used for detection of the fire blight pathogen in extracts of tissue obtained from infected plant material.

Base Sequence↗
PubMed1992

[Prevalence of hepatitis C virus in poly-transfused patients with hematologic and oncologic diseases].

Patients with hematological and oncological diseases often require intensive, supportive hematotherapy due to the underlying disease or chemo-/radiotherapy. As a consequence, they had an increased transfusion-associated risk of hepatitis C virus infections (non-A, non-B-posttransfusion hepatitis) until 1989-1990, when specific and sensitive HCV antibody tests became available. This is confirmed by our study of 'first' and 'second' generation (1.0 and 2.0) anti-HCV EIAs against structural and non-structural (NS) antigen-determinants. Ten of 101 patients (10.9%) were anti-HCV positive in 2.0 tests. HCV antibodies were detected more often by 2.0 EIAs and the new HCV-immunoblot (4-RIBA), than by 1.0 EIAs. In this respect, the patients' serological HCV profile differs from that of healthy blood donors, which display a prevalence of NS-antibodies.

Adolescent↗
PubMed1992

Pharmacodynamic and pharmacokinetic aspects of iodo-doxorubicin.

Iodo-doxorubicin (I-DOX) is a new doxorubicin (DOX) analog presently in phase II clinical trials in Europe. This drug is similar to DOX in its metabolism but differs in its pharmacokinetics. We describe correlations between pharmacokinetic parameters and toxicity. There is a linear relationship between the dose in mg/m2 and the nadirs of the reduction in white blood cells (WBC), neutrophils (PMN), platelets (PLT), and hemoglobin (HB). Furthermore, a linear correlation exists between the dose in mg/m2 and the area under the curve (AUC) of I-DOX. The relationship between the AUC of I-DOX and the reduction of PMNs plotted on a logarithmic scale shows a sigmoidal curve, whereas no such correlation was found between I-doxorubicinol, the major cytostatic metabolite, and the reduction in PNMs. The variation in the AUC for I-DOX correlated with the relative amount of metabolism of I-DOX. A correlation existed between the relative amount of metabolism of I-DOX and the reduction in PNMs. These results may have an impact on the evaluation of I-DOX in phase II trials, since a sound understanding of the pharmacokinetic/pharmacodynamic relationships can yield important information for minimizing unacceptable toxicity during phase II, as well as phase III, trials.

Biotransformation↗
PubMed1991

A phase II combination trial with recombinant human tumor necrosis factor and gamma interferon in patients with colorectal cancer.

Recombinant human tumor necrosis factor (TNF) is a cytotoxic monokine with immunomodulatory functions. Gamma interferon (g-IFN) synergizes with TNF in many ways. We therefore conducted a Phase I/II combination trial with TNF and g-IFN at an immunomodulatory dose level in 16 patients with colorectal cancer. TNF (50 micrograms/m2 in a 30 min infusion) and g-IFN (100 micrograms in subcutaneous injections) were administered daily Monday through Friday for 4 weeks. Two cases of major toxicity, one acute renal failure and one case of severe thrombocytopenia, led to discontinuation of study medication in these patients. Toxicities in remaining patients were manageable with conservative treatment. Changes in laboratory values included leukopenia, anemia and thrombocytopenia. Alterations in lipid metabolism and changes in serum levels of acute phase proteins were observed. Increase in both total lymphocytes and a Leu 11 positive subpopulation, as well as an induction of measurable interleukin 2 serum levels in a subgroup of patients, were noted. Response results of 14 evaluable patients were one patient with a mixed response, 4 with stable disease and 9 with disease progression. Median survival was 23.5 weeks with only one patient alive after 71 weeks. Therefore the drug combination of TNF/g-IFN in the chosen regimen cannot be recommended for the treatment of patients with colorectal cancer.

Adult↗
PubMed1991

Translocation (14; 18) and (8; 22) in three patients with acute leukemia/lymphoma following centrocytic/centroblastic non-Hodgkin's lymphoma.

Three patients with centrocytic/centroblastic lymphoma developed a rapidly fatal leukemic transformation of the disease after a transient remission. At the time of transformation, cytogenetic analysis revealed in all patients abnormal karyotypes with coexistence of t (14; 18) and t (8; 22). Molecular analysis in one patient showed rearrangement of the BCL 2 oncogene and c-myc m-RNA expression. These findings imply that translocation t (14; 18) was present during the first phase of the disease and that acquisition of translocation t (8; 22) was accompanied by leukemic transformation.

Acute Disease↗