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A Drivsholm

Publications and source records attributed to A Drivsholm.

At least 19 recordsLinked to original sources
PubMed1992

Mouse erythrocyte rosette formation with malignant human B-lymphocytes re-evaluated: still a useful marker for differentiating mature B-cell malignancies.

We have re-evaluated mouse rosette formation (MRF) as a marker for B-CLL by estimating the fraction of mouse rosette forming B-lymphocytes (identified by CD20 monoclonal antibodies) in normal donors and malignant CD20+ cell proliferations (ALL, AML, B-NHL, B-HCL and B-CLL). Whereas this ratio was increased in B-CLL, all other CD20 positive malignancies showed mean ratios of less than 0.1. As part of a Danish multi-centre study, we furthermore prospectively analysed 86 patients and found that the mouse/CD20 ratio divided the 78 patients with monoclonal B-cell populations suspected of B-CLL in two distinct groups. In the low ratio group, three patients were categorized as leukaemized B-NHL and one as PLL. The remaining three patients with low ratio were clinically and immunologically (by SmIg density and CD5 expression) B-CLL patients suggesting a frequency of MR-negative B-CLLs of approximately 5%. In the high ratio group two of 70 patients were diagnosed as B-NHLs. Thirdly, MRF was a valuable parameter in patients, where transformation of disease is suspected, since it preceded clinical changes by several months. Thus, MRF is still a useful marker in the age of monoclonal antibodies.

Adult↗
PubMed1991

Aberrations of chromosome 6 in 193 newly diagnosed untreated cases of chronic lymphocytic leukemia.

Aberrations of chromosome 6 were observed in 11 of 193 cases of chronic lymphocytic leukemia diagnosed January 1, 1984-November 1, 1988 and investigated cytogenetically within 30 days after diagnosis. The 6p was rearranged in 5 cases: 4 balanced and 1 unbalanced translocation. The 6q was involved in 6 cases: 4 deletions and 2 balanced translocations. Three of the del(6q) may be identical: del(6)(q13q27). In two cases there were no additional aberrations. Aberrations of chromosome 6 correlated significantly with an advanced clinical stage, diffuse pattern of bone marrow infiltration, and increased SmIgM-fluorescence intensity. All these factors are associated with poor prognosis. Although the number of cases with 6q aberrations is still too small and the observation period too short to show significant influence on survival, the presence of 6q aberrations at diagnosis may prove useful in delineating a subtype of chronic lymphocytic leukemia with poor prognosis.

Bone Marrow↗
PubMed1991

Immune dysfunction in multiple myeloma. Reduced natural killer cell activity and increased levels of soluble interleukin-2 receptors.

Multiple myeloma (MM) is characterized by an increased susceptibility to infections and to other malignancies. Selected related immune functions were studied. Spontaneous and interleukin-2-stimulated natural killer (NK) cell activities were normal in 19 patients with MM compared with 62 controls. In contrast, interferon-stimulated NK cells had a significantly lower increase in activity in MM than in controls. The normal improvement in lytic NK cell activity after addition of indomethacin to the mononuclear cell cultures (to inhibit prostaglandin-mediated suppression) was not observed in cultures from MM patients. As reported for other lymphoproliferative disorders, the levels of soluble interleukin-2 receptors in serum were significantly higher in MM (600 U/ml median value) compared with controls (317 U/ml median value), P less than 0.0001, and the concentration of interleukin-2 receptors was significantly correlated with the concentration of monoclonal immunoglobulin in serum. Blood monocyte chemotactic responsiveness was significantly lower in MM patients with both zymosan-activated serum and f-Met-Leu-Phe as cytotaxins, suggesting reduced ability to accumulate at inflammatory foci. In contrast, release of reactive oxygen radicals, believed to be associated with the killing ability of monocytes, was normal after in vitro stimulation.

Aged↗
PubMed1991

Aclarubicin plus cytosine arabinoside versus daunorubicin plus cytosine arabinoside in previously untreated patients with acute myeloid leukemia: a Danish national phase III trial. The Danish Society of Hematology Study Group on AML, Denmark.

A regimen of aclarubicin (ACR) of 75 mg/m2 daily for 3 days plus a continuous intravenous infusion of cytosine arabinoside (ara-C) of 100 mg/m2 per day for 7 days was compared with daunorubicin (DNR) 45 mg/m2/day for 3 days plus ara-C for 7 days as first-line chemotherapy of de novo acute myeloid leukemia (AML) in a randomized, nationwide Danish study. A total of 180 patients aged between 17 and 65 years were entered onto the protocol. Patients who achieved complete remission (CR) were given five courses of intensive consolidation therapy consisting of two courses of high dose ara-C, two courses of amsacrine plus etoposide, and one course of DNR plus ara-C. Of 174 evaluable patients, 99 achieved CR. The rate of CR was significantly higher on ACR plus ara-C than on DNR plus ara-C [66% versus 50% (p = 0.043)] and decreased significantly with increasing age. The hematological toxicity was identical for the two regimens. A total of 83 patients entered consolidation therapy. At 4 years, 37% of patients with CR following ACR were still in remission compared with 33% following DNR (p = 0.48), and the total survival at 4 years was 29% versus 20% (p = 0.26). The duration of remission and total survival both decreased with increasing age. ACR plus ara-C seem at least as good or better than DNR plus ara-C as first-line chemotherapy of AML.

Aclarubicin↗
PubMed1990

Decreased tetranectin in multiple myeloma.

Tetranectin, a recently described human protein widely distributed in the body and with possible importance for cell growth and differentiation, has previously been observed to be decreased in patients with solid malignant tumors. In patients with multiple myeloma, either untreated or previously treated, serum levels were found to be significantly reduced. A negligible interindividual variation was observed. Levels of serum tetranectin were not correlated with serum albumin, hemoglobin, or M-component. Low levels of tetranectin may be related to the growth and spread of malignant cells or reflect a general catabolic state of chronic disease.

Aged↗
PubMed1990

The effect of ranitidine on cellular immunity in patients with multiple myeloma.

Multiple myeloma is characterized by an increased susceptibility to infections and to other malignancies. In a double-blind, placebo-controlled study the potential impact of immunomodulation by ranitidine was studied in 20 patients with multiple myeloma. Three patients were untreated, while 17 after previous cytotoxic therapy were in a stable phase of their disease. All were without clinical signs of infections and at that time had not been treated with other immunomodulating agents. The patients were randomized to oral ranitidine 300 mg twice a day for 21 days or placebo, and several immunological parameters related to multiple myeloma were studied. The blood monocyte chemotactic response was improved in patients treated with ranitidine, and superoxide anion production increased from 2.02 nmol/min to 3.86 nmol/min (median values), while it was unchanged in patients given placebo (2.19-2.25 nmol/min) (P less than 0.005 between groups). Among ranitidine-treated patients spontaneous NK cell activity was unchanged, while in vitro interleukin-2- and interferon-alpha-stimulated NK cell activity decreased (P less than 0.03, respectively). As production of oxygen radicals constitutes an important mechanism of monocyte killing activity against microorganisms and probably against malignant cells, it is suggested that ranitidine may be of beneficial impact in the treatment of multiple myeloma.

Adjuvants, Immunologic↗
PubMed1990

The secretory erythropoietin response in patients with multiple myeloma and Waldenström's macroglobulinaemia.

Immunoreactive levels of serum erythropoietin (EPO) have been measured in 95 patients with multiple myeloma (MM) and 12 patients with Waldenström's macroglobulinaemia (MW). Of the MM patients 23% were uraemic (mostly light and moderate renal failure) and 61.7% were anaemic. In the anaemic nonuraemic MM patients the mean serum EPO titre was 106.8 +/- 30.4 mU/ml which, when related to the extent of anaemia, was found to be appropriately elevated for the degree of anaemia (the mean haemoglobin (B-HGB) concentration was 6.66 +/- 1.31 mmol/l). The mean serum EPO concentration in uraemic and anaemic MM patients was 39.2 +/- 9.2 mU/ml, which was markedly lower than serum EPO levels in the non-uraemic MM patients, but still higher than in nonanaemic control subjects (22.5 +/- 8.5 mU/ml). The mean B-HGB concentration in uraemic MM patients was 6.04 mmol/l. In the anaemic MM patients with severe renal failure (S-creatinine levels greater than 400 mumol/l) the compensatory secretion of EPO was inadequate in relation to the degree of anaemia. The data indicate that unless the hypoproliferative anaemia of MM is accompanied by considerable renal failure the anaemia does not appear to be associated with a deficient biogenesis of EPO. Likewise the anaemia found in patients with MW also seems, generally, to elicit an appropriate increase in EPO secretion. Reasonably clinically stable MM patients with anaemia and uraemia may be candidates for replacement therapy with recombinant human erythropoietin (rhEPO).

Anemia↗
PubMed1989

B lymphocyte function in multiple myeloma: analysis of T cell- and monocyte-dependent antibody production.

T-cell and B-cell functions were studied in 35 patients with untreated multiple myeloma (MM) and in 16 patients with MM treated with prednisolone, melphalan and vincristine. The numbers of CD4+ T cells were normal in untreated MM patients, but markedly decreased in treated patients, whereas CD8+ cell numbers were normal in untreated and treated patients. Mitogen-induced as well as antigen-induced lymphocyte proliferative responses were reduced, but not further affected by treatment. The antigen-induced proliferative responses by lymphocytes of treated, but not of untreated patients, correlated positively to the proportions of CD4+ cells among MNC. Taken together, the findings suggest selective loss of CD4+ subpopulations during cytotoxic treatment. Pokeweed mitogen (PWM)-induced Ig production was generally low, but significantly reduced Ig production was only seen in experiments employing MM B cells and monocytes co-cultured with irradiated T-enriched cells. Irradiated MM T cells displayed normal helper function when co-cultured with normal B cells stimulated with PWM. MM B cells and monocytes cultured with irradiated normal T cells produced little Ig; however, MM monocytes were not suppressive. In 2 of 3 patients with either IgG-kappa or IgA-kappa myeloma, the numbers of PWM-stimulated B cells that produced kappa chains were somewhat higher than those found among normal MNC. The impaired ability of antibody production by B cells from untreated MM patients seems to relate to intrinsic B cell defect(s) rather than to abnormal regulation by T cells or monocytes. However, disturbances in the functions of CD4+ cells may be observed in treated MM.

Aged↗
PubMed1988

Occurrence and type of chromosomal abnormalities in consecutive malignant monoclonal gammopathies: correlation with survival.

Chromosome studies were done on 73 patients with multiple myeloma and three patients with plasma cell leukemia. Eighteen of 76 patients (24%) had chromosomally abnormal clones, including all three patients with PCL. The most common anomalous chromosomes were #1, #14, and #12. In addition, i(17q) was found in two patients with plasma cell leukemia. Among newly diagnosed patients there was no difference in survival for those with abnormal karyotypes and those with normal karyotypes. Among previously diagnosed patients receiving treatment, however, individuals with an abnormal clone had a significantly higher mortality during the first 2 years compared to those with a normal clone. Patients with no growth of metaphases in their bone marrow aspirate had a significantly lower mortality than other patients (p less than 0.05).

Chromosome Aberrations↗
PubMed1988

The CLL2 study: preliminary results of flow cytometry immunophenotyping in the first 500 patients.

In the period 1984-1987, 500 consecutive, newly diagnosed patients with chronic lymphocytic leukaemia (CLL) have been registered in the still open Danish CLL2-study. As part of patient work-up, the immunological phenotype was established in all patients by immunofluorescence microscopy, and in 458 patients also by flow cytometry, with a panel of polyclonal and monoclonal antibodies. The majority of cases exhibited a CD5-pos, SmIgMD-pos phenotype with faint SmIg-fluorescence, and there is as yet no significant difference in survival between SmIgD-pos and SmIgD-neg cases. Seventy cases were FMC7-pos, a marker associated with a higher B-cell differentiation, and this was significantly correlated with stronger SmIg fluorescence intensity and splenomegaly (Rai stage II). The survival of the FMC7-pos patients was not significantly different from that of the FMC7-neg. Thus, in this preliminary phenotype analysis of the first 500 patients in the CLL2 study, no important prognostic subgroups were detected, although this might be due to the still short observation time (median observation time 532 days).

Denmark↗
PubMed1986

Non-Hodgkin malignant lymphomas and Hodgkin's disease in first-degree relatives. Evidence for a mutual genetic predisposition?

The occurrence of malignant lymphomas in 3 siblings is described. The cases include the first report of Hodgkin's disease and non-Hodgkin malignant lymphoma in dizygotic twins. Another remarkable feature was the development of malignant lymphoma, when the siblings were at the same age. Although a transmissible agent or environmental factors cannot be excluded in this family, our observations may suggest a mutual genetic predisposition in Hodgkin's disease and non-Hodgkin malignant lymphoma.

Adult↗
PubMed1985

Development of acute nonlymphocytic leukaemia (ANLL) in myelomatosis.

On the basis of the literature, so-called secondary acute nonlymphocytic leukaemia (S-ANLL) in myelomatosis is reviewed. Using the banding technique, cytogenetic changes including hypodiploidy and partially or totally missing chromosomes # 5 and # 7 are recorded. The findings are in accordance with the cytogenetic changes seen in S-ANLL in other malignancies which have been treated with cytostatics, especially alkylating agents. So, S-ANLL in myelomatosis seems to be a result of treatment with cytostatics, though a causal relationship has to be documented.

Acute Disease↗
PubMed1985

Phase III study of intermittent 5-drug regimen (VBCMP) versus intermittent 3-drug regimen (VMP) versus intermittent melphalan and prednisone (MP) in myelomatosis.

A prospective randomized trial in 96 patients with previously untreated myelomatosis was performed comparing 3 regimens of chemotherapy: (i) Intermittent vincristine, BCNU, cyclophosphamide, melphalan, and prednisone (VBCMP) to (ii) intermittent vincristine, melphalan and prednisone (VMP) to (iii) intermittent melphalan and prednisone (MP). Induction response rates and survival were similar in all 3 regimens. An improvement in relapse-free survival was observed by adding vincristine to MP, but this did not achieve statistical difference (p = 0.10). Patients given VBCMP fared slightly worse than those given VMP. The haematologic toxicity was similar in all 3 regimens, but the tolerability of VBCMP was lower. Although showing no statistical differences between the 3 treatment regimens, the results support the view that a combination of MP 'standard' induction therapy in MM with frequently administered vincristine has a trend towards postponing treatment failure due to development of resistance to melphalan.

Adult↗
PubMed1978

Interrelationships between Vitamin B12 and folic acid in myelomatosis: cobalamin coenzyme and tetrahydrofolic acid function.

Cobalamin and folate metabolism was investigated in 43 patients with myelomatosis, in 8 control subjects of similar age and 22 younger controls. Plasma total cobalamin was lower in myeloma patients than in either of the control groups and methylcobalamin (Me-Cbl) was disproportionately reduced. Erythrocyte levels of total cobalamin were very similar in patients and elderly controls but were half the levels in younger controls. Erythrocyte levels of Me-Cbl were slightly higher in patients than in the dlderly controls. FIGLU excretion after L-histidine was elevated in 53% of the patients but values did not correlate with serum or erythrocyte folate or with plasma total cobalamin. FIGLU excretion decreased after DL-methionine or Me-Cbl only in patients whose FIGLU excretion was initially high. The results are discussed in the light of the 'methylfolate trap hypothesis' and suggest that some patients with myelomatosis have insufficient activity of methionine synthetase to meet the additional metabolic demand for one carbon compounds.

Adolescent↗
PubMed1977

[Hematology].

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Bone Marrow Transplantation↗
PubMed1977

Vitamin B12 metabolism in myelomatosis.

In 38 patients with myelomatosis the serum cobalamin varied from 34 pmol/1 to 404 pmol/1, median 181.5 pmol/1, which is significantly lower than the levels in 22 control persons with range 173-535 pmol/1, median 265 pmol/1. In spite of low serum cobalamin no symptoms of vitamin B12 deficiency could be demonstrated in any of the patients, except for the one patient who had a serum cobalamin of 34 pmol/1. Mean values for Hb, MCV, PCV, serum lactate-dehydrogenase, adjested red cell folate and nucleated neutrophil count were similar in a group of patients with a serum cobalamin below 160 pmol/1 and a group of patients with higher serum cobalamin values. The decrease in serum cobalamin is due in part to a reduction in the major cobalamin binder (TC-I) in serum. Measuring serum cobalamin in relationship to gastric acis secretion, we found a significantly higher frequency of hypo- and achlorhydria in patients with serum cobalamin below 160 pmol/1 although the intestinal absorption of vitamin B12 was normal by a Schilling test. Although our finding of low saturation of TC-I in serum seems to demonstrate decreased vitamin B12 content in the body in myelomatosis, the lack of evidence for a functional vitamin B12 deficiency speaks against giving a supplement to patients with myelomatosis.

Aged↗
PubMed1977

Serum erythropoietin in myelomatosis.

Erythropoietin activity in serum was measured using 59Fe incorporation into erythrocytes in protein-starved, hypoxic mice. The activity in serum from 20 patients with untreated myelomatosis was not significantly different from that in 31 saline controls. Only three patients had detectable erythropoietin levels in serum: 0.24 IU/ml, 0.27 IU/ml and 0.50 IU/ml (standard B), respectively. The venous haematocrit was correlated positively with the glomerular filtration rate as measured by 51Cr EDTA-clearance. No correlation could be established between venous haematocrit and serum albumin or serum transferrin. The results are in agreement with the assumption of a defective erythropoietin activity due to renal failure in myelomatosis.

Erythropoietin↗