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J Ellegaard

Publications and source records attributed to J Ellegaard.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Diagnosis of minimal residual disease in autologous bone marrow transplantation].

ABMT (autologous bone marrow transplantation) is being increasingly used in the treatment of malignant diseases, including the acute leukaemias. Although ABMT seems to be superior to conventional chemotherapy in terms of disease-free survival, an unacceptably high frequency of relapse after ABMT remains a major problem. As such relapse may be due to malignant cells in the graft or residual malignant cells surviving in the patient after preconditioning therapy, it is essential to be able to detect and eradicate residual malignant cells. The article presents a review of available methods for the detection of minimal residual disease in conjunction with ABMT, especially regarding their relative sensitivity and specificity.

Acute Disease↗
PubMed1995

[Erythropoiesis in myelodysplastic syndrome detected by multiparameter flow cytometry].

By staining human bone marrow cells with a monoclonal antibody reacting with surface antigens on erythroid precursor cells (AS-E1) and with propidium iodide reacting with nuclear DNA, we have evaluated the proliferative activity of erythropoiesis in patients with myelodysplastic syndromes using flow cytometric analysis. Comparing 36 patients (13 RA/RAS, 13 RAEB, 10 RAEB-t) with seven normal controls, significant differences in both the percentage of erythroid precursor cells and the fraction of these cells in the S or S-G2M-phase of the DNA cell cycle between the four groups were found. Since neither the percentage of erythroid precursor cells nor their fraction in S or S-G2M phase alone was found to characterize their proliferative activity, we calculated the proliferative fractions of the erythroid cells, i.e. the number of the erythroid precursor cells in S or S-G2M related to all bone marrow cells in S or S-G2M phase. Applying these parameters, we found significantly increased proliferative fractions of erythroid precursor cells in the RA/RAS patients compared to the normal controls (p-0.03 and 0.002 respectively), as well as a highly significant decrease with disease progression.

Cross-Sectional Studies↗
PubMed1995

Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial.

OBJECTIVES: To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers. DESIGN: Randomised, double blind, placebo controlled trial. SUBJECTS: 74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days. MAIN OUTCOME MEASURES: Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis. RESULTS: The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)). CONCLUSION: Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.

Acute Disease↗
PubMed1995

Differential expression levels of the heat shock protein 27 isoforms in pediatric normal, nonleukemic and common acute lymphoblastic leukemia B-cell precursors.

Heat shock protein 27 (hsp27) may function as a regulator of microfilament dynamics and may participate in signal transduction pathways of different cell growth regulators, with the mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 being a major enzyme responsible for its phosphorylation. Using two-dimensional gel electrophoresis, we have compared the expression levels of two hsp27 isoelectric variants (hsp27 isoforms) M2 (molecular weight, 26 kD; isoelectric point, 6.02) and M3 (molecular weight, 26 kD; isoelectric point, 5.60) in pediatric bone marrow CD19+CD10+B-cell precursors (BCPs) purified from either common acute lymphoblastic leukemia (c-ALL) patients, normal donors, or non-c-ALL patients. Compared with normal BCPs, we found increased hsp27 expressions (M2 isoform) (by a factor 5 to 9 of mean level) in c-ALL as well as in non-c-ALL (nonleukemic) precursors. Though increased phosphorylation of hsp27 (M3 isoform) was observed in BCPs from c-ALL patients at relapse (by a factor 3 of mean level compared with normal BCPs and precursors from c-ALL at diagnosis), which might represent a differential enzymatic activity, this was not distinguishable from that of non-c-ALL patients. Therefore, our studies suggest constitutive differences of hsp27 isoforms between pediatric leukemic BCPs and their relatively low-expressing, immunophenotypically normal bone marrow counterparts. In light of the occasional and possibly transient increase of hsp27 expression during nonleukemic BCP differentiation and the possible role of hsp27 in signal transduction to microfilaments, these differences might be of considerable biologic interest and of importance in future studies of regulated normal or dysregulated leukemic hematopoietic cellular differentiation.

Adolescent↗
PubMed1995

Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassaemic patients.

The ability to quantitate transfusional iron overload is crucial for determining the need for and the efficacy of chelation therapy in patients with long-standing transfusion-dependent anaemias. We evaluated the usefulness of some indirect measures of iron overload in estimating the iron concentration in the liver--the most important iron storage organ--in 26 non-chelated adult non-thalassaemic patients. Liver iron concentration was determined non-invasively by magnetic resonance imaging (MRI). The standard error of the estimated liver iron concentration was 80 mumol Fe/g dried liver tissue when using the number of transfused blood units, and 93 mumol Fe/g when using a serum ferritin assay. Follow-up in 11 patients (12-48 months) revealed that serum ferritin is a poor measure of the liver iron concentration during iron chelation. However, this discrepancy was individually different and seemed to be dependent on the erythropoietic marrow activity. By monitoring the liver iron concentration by MRI, we compared the efficacy of chelation with desferrioxamine given either by subcutaneous continuous infusions or by bolus injections. Depletion of liver iron stores could be achieved efficiently by both regimens.

Adolescent↗
PubMed1994

A factor encoded by 7q31 suppresses expansion of the 7q- clone and delays cytogenetic progression.

Deletion of part of chromosome 7q (7q-) is a consistent aberration in human acute leukemias and myelodysplasias, especially in patients with a history of genotoxic exposure. The deletion is usually associated with a short survival. Loss of a number of different 7q segments has been described, but still it is not known whether different deletions imply differences in survival. We have investigated the possible importance of loss of different segments in 77 7q- patients studied with high-resolution banding. Thirty-six were examined in our laboratory and 41 were published cases. We found that when the 7q- marker contained the 7q31 band, the 7q- clone was smaller than when the band had been lost (p = 0.011), and the patients survived longer (p = 0.004). Further, karyotypes with complex aberrations were less frequent (p = 0.012). These results indicate that genetic information in 7q31 delays cytogenetic and clinical progression of myeloid disease with 7q-. Our results do not tell, however, whether this is due to direct tumor suppressor activity of a 7q31 gene or due to a more indirect effect.

Adolescent↗
PubMed1994

Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging.

We investigated the clinical usefulness of a standard magnetic resonance imaging (MRI) system for non-invasive determination of the liver iron concentration in 38 patients with iron overload and 15 normal controls by measurement of the signal intensity ratio between liver and skeletal muscle (SIR). However, SIR was found dependent on the applied repetition time (TR) of the MRI system, which led us to investigate this relationship in autopsy material of liver and muscle tissue specimens with various iron content. Based on these results, adjustment of SIR measurements to a constant value of TR was achieved. By use of this technique we found a close correlation between MRI and chemically determined liver iron concentration (r2 = 0.98) as well as the serum ferritin concentration (r2 = 0.86). The reproducibility was sufficiently good for the use of MRI in the follow-up of iron reductive treatment. The use of iron store parameters in serum was found insufficient as indicators of endpoint for venesection therapy, if 20 mumol Fe/g dry weight was applied as the upper reference limit of the liver iron concentration. It is concluded that MRI based on SIR measurements offers a precise and reproducible non-invasive method for the determination and follow-up of iron overload within a wide range of liver iron concentrations. Our findings may increase the clinical use of MRI in haematological patients with iron overload.

Bloodletting↗
PubMed1994

The effect of iron overload and iron reductive treatment on the serum concentration of carbohydrate-deficient transferrin.

The concentration of carbohydrate-deficient transferrin in serum (CDT) has been used as a reliable indicator of recent alcohol consumption. We have investigated the utility of this laboratory test in 20 patients with hereditary haemochromatosis (HH) by simultaneous evaluation of serum concentrations of liver transaminases, gamma-glutamyl transpeptidase, iron, transferrin and assessment of the liver iron concentration by magnetic resonance imaging. 11 patients were re-examined during iron depletion with phlebotomies. In all 11 patients intensive but not maintenance iron removal was associated with an increase in serum CDT, in three patients even to levels above the reference range. The mean serum CDT increased from 8.5 (SD 2.2) U/l to 16.6 (SD 7.2) U/l (P < 0.001). Iron mobilization from the liver was found particularly responsible for the increase in serum CDT. Independent of this finding we found a significant semi-logarithmic correlation (r = -0.77, P = 0.009) between the MRI determined liver iron concentration and serum CDT in the patients not on iron depletion. Our findings indicate that the utility of serum CDT as a measure of alcohol consumption in patients with HH may be compromised, especially during intensive iron depletion.

Adult↗
PubMed1993

Differences in relative DNA content between human peripheral blood and bone marrow subpopulations--consequences for DNA index calculations.

By sequentially staining for leukocyte differentiation antigens with monoclonal antibodies and for stainable DNA content with propidium iodide, we have evaluated the DNA ratios of normal peripheral blood and bone marrow subpopulations. In 19 peripheral blood samples the relative DNA content of the monocytes was higher than that of other subpopulations, with highly significant differences between the DNA ratios of the CD14+ monocytes, on the one hand, unlabeled controls, CD3+ T-lymphocytes, and CD20+ B-lymphocytes, on the other. In bone marrows from 16 healthy volunteers, the relative DNA content of the myelomonocytic subpopulations was higher than that of the T-lymphocytes with significant differences between the CD3+ lymphocytes, on the one hand, and the CD14+ monocytes, the CD13+ and CD33+ immature myeloid, the NAT9+ mature myeloid, and the AS-E1+ nucleated erythroid subpopulation, on the other. Since a mixture of peripheral blood mononuclear cells or T lymphocytes from healthy volunteers is often used as an external standard for DNA ploidy determinations, these data suggest that such a procedure could result in an overestimation of the DNA indices of most of the bone marrow subpopulations. Instead, we suggest the use of the DNA ratio of the CD14+ subpopulation from peripheral blood as standards for ploidy determinations for the myeloid bone marrow subpopulations.

Antibodies, Monoclonal↗
PubMed1993

Synergistic and antagonistic effects of myeloid growth factors on in vitro cellular killing by cytotoxic drugs.

The effect of stimulating acute myeloid leukemia blast cells with a combination of growth factors (G-CSF, GM-CSF, and IL-3) on cellular resistance to the antileukemia drugs Ara-C, daunorubicin, aclarubicin, and mitoxantrone was studied. For assessment of in vitro cellular drug resistance the MTT assay was employed. Stimulated cells showed enhanced sensitivity to Ara-C (p < 0.02), whereas a significant increase in cellular drug resistance to daunorubicin (p < 0.02) was observed. Variable and statistically non-significant changes in drug resistance to aclarubicin and mitoxantrone was induced by stimulation of the blast cells. We conclude on the basis of these observations that myeloid growth factors should be used with caution in combination with daunorubicin in AML treatment until further confirmatory evidence has been presented by other investigators.

Aclarubicin↗
PubMed1993

Heart transplantation in a case of juvenile hereditary haemochromatosis followed up by MRI and endomyocardial biopsies.

Cardiac involvement in hereditary haemochromatosis (HH) is a poor prognostic sign and is the main cause of death in the juvenile form. The treatment of choice is iron removal therapy by phlebotomy, but treatment by iron chelation (desferrioxamine) has been recommended in cases with severe cardiac symptoms. We describe here the first case of juvenile HH undergoing heart transplantation, which became necessary despite intensive iron removal therapy by phlebotomy and treatment by desferrioxamine. Throughout the course the myocardial iron content was monitored by endomyocardial biopsies and by magnetic resonance imaging (MRI). At the last follow-up, 18 months after transplantation, the myocardial iron content in the transplanted heart was still within reference ranges by biochemical determination and MRI and the patient's condition was completely satisfactory. In conclusion, heart transplantation should be considered in cases of severe juvenile HH. In the follow-up of these patients MRI may be a useful supplement.

Adult↗
PubMed1993

Multiple myeloma treated with mitoxantrone in combination with vincristine and prednisolone (NOP regimen) versus melphalan and prednisolone: a phase III study. Nordic Myeloma Study Group (NMSG).

One-hundred-and-fifty-one patients with previously untreated multiple myeloma were allocated to treatment with either NOP regimen (mitoxantrone 16 mg/m2 and vincristine 2 mg day 1 and prednisolone 250 mg day 1-4 and 17-20) or M+P regimen (melphalan 0.25 mg/kg and prednisolone 100-200 mg/day day 1-4). Both regimens were repeated every 4 weeks and were scheduled for 1 year. Seventy-seven patients were treated with NOP and 74 patients with M+P. No major clinical differences were recorded between the groups before treatment. Sixty percent of the patients responded (CR+PR) to NOP versus 64% to M+P (NS). The time to progression was 16 months (95% C.L. 14-51) in the NOP group versus 21 months (95% C.L. 15-27) in the M+P group (NS). The median survival was 14 months (7-21) in the NOP group and 31 months (21-43) in the M+P group (p = 0.02). NOP was significantly more toxic than M+P. Seven patients treated with NOP died due to infection and neutropenia and 1 patient died of cardiac toxicity, in contrast to 1 death due to infection and neutropenia in the M+P group. Gastrointestinal toxicity was acceptable in both groups. In conclusion, NOP was inferior to M+P as primary treatment of multiple myeloma.

Adult↗
PubMed1993

Optimization of a method for simultaneous analysis of cell surface phenotype and cell cycle in human bone marrow and peripheral blood leukocytes by flow cytometry: the value of both internal and external standards.

Three different methods for the simultaneous analysis of surface phenotype and DNA quantification were compared. One method, involving the fixation of cells in 70% ethanol, was convincingly superior, both with regard to the CV of the G0G1 peak and the intensity of the DNA labelling. Furthermore, the correlation between the surface antigen densities before and after fixation were high. Experiments evaluating the intraday and the interday variation of the DNA ratio (the mean channel of the G0G1 peak of the sample divided by the mean channel of the G0G1 peak of chicken erythrocytes), documented the former to be small, with S.D. values varying from 0.0 to 0.016, while the latter were considerably higher with S.D. values varying from 0.077 to 0.123. Since the intraday variation of the DNA ratio was consistently low and the interday variation strongly correlated to the position of the red fluorescence test beads, it was possible to minimize the interday variation of the DNA ratio, by calculating the DNA index as the ratio between the DNA ratio of the sample and that of an external control (buffy coat leukocytes). Analyzing normal bone marrow and calculating the DNA index (DI) on the basis of these ratios, the confidence limits of the DI were decreased by more than half the values obtained when DI calculation was based solely on an internal standard, thereby making subsequent ploidy determinations of patient samples more precise. We conclude that this setup of internal and external standards allows accurate determinations of DNA aneuploidy even in an assay where whole cells labelled for surface antigen and DNA content are analyzed.

Animals↗
PubMed1992

[Granulocyte-macrophage colony-stimulating factor. Treatment of patients with highly malignant lymphomas and acute lymphoblastic leukemias after autologous bone marrow transplantation].

We have evaluated the effect of intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) in ten patients undergoing autologous bone marrow transplantation after total body irradiation (11 Gy) and cyclophosphamide (120 mg/kg) conditioning for malignant lymphomas or acute lymphoblastic leukaemias. Mild side effects related to GM-CSF were seen in six patients, of whom one chose to discontinue treatment. Compared to a historic control group consisting of six patients treated with an identical conditioning regimen, a tendency was seen towards a more rapid neutrophil regeneration and a decreased need for erythrocyte transfusions. Moreover, a statistically significant improvement in thrombocyte related parameters was demonstrated. In contrast, there were no significant differences in severe toxicity, days on i.v. antibiotics, septic episodes or duration of hospitalization. In conclusion, it seems that GM-CSF treatment is of value in patients undergoing AKMT.

Adolescent↗