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Biomedical subjects

B E Christensen

Publications and source records attributed to B E Christensen.

At least 19 recordsLinked to original sources
PubMed1992

Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia.

The reciprocal translocation (9;22)(q34;q11) is highly characteristic of chronic myeloid leukemia (CML) and the pericentric inversion inv(16)(p13q22) is almost only found in acute nonlymphocytic leukemia of the myelomonocytic subtype (ANLL M4). Only twice before have an inv(16) and a t(9;22) been found in the same cells, and both times the patients seemed to have de novo ANLL M4. We describe the case of a 21-year-old man who in July 1986 presented with a clinically and hematologically classic chronic phase CML. Treatment with busulfan led to no improvement; instead in September 1986 he developed blast crisis with ANLL M4Eo morphology. He was now cytogenetically examined and the karyotype 45,X,-Y,t(9;22)(q34;q11),inv(16)(p13q22) was found. Southern blot analysis of the bone marrow DNA sampled at this time revealed a standard rearrangement in the 3' end of the M-bcr. Intensive cytostatic treatment caused cytopenia followed by complete hematologic, clinical, and cytogenetic reversal to chronic phase CML, so that in January 1987 the bone marrow karyotype was 46,XY,t(9;22)(q34;q11). Persistent splenomegaly was treated with splenectomy, and a chloroma of the skin was removed by irradiation. In March 1987 he received an allogeneic bone marrow transplant. Since then his only medical problem has been mild graft-versus-host disease; he is well and is working full time as a blacksmith.

Adult↗
PubMed1992

Non-Hodgkin's lymphoma in the elderly. A study of 602 patients aged 70 or older from a Danish population-based registry. The Danish LYEO-Study Group.

Within a 7-year period 1,597 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) were included in a Danish population-based NHL registry. Of these, 602 (38%) were aged 70 years or older (age range 70-94, median: 76.8). They represent the population defined as 'elderly' patients in the present study. The average annual incidence rate for this elderly patient population was 35.7/10(5), as compared with 6.6/10(5) for patients aged less than 70 (overall annual incidence: 9.5/10(5)). Localised cases (stage I and II) and extranodal manifestations were found more frequently among elderly patients. The most common sites of extranodal involvement were the stomach (21% of all extranodal cases) and the bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p less than 0.01) in elderly patients as compared to their younger counterparts (less than 70 years), who in contrast had a lower occurrence of diffuse centroblastic cases (p less than 0.01). Overall 7-year survival for the elderly patient population was 35% (median 1.7 years), and for patients aged less than 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66%, respectively, p less than 0.0001). Elderly patients with poor prognosis were characterised by the following features identified in a Cox-regression model: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were in the order 2.4, 2.2, 1.9 and 1.6.

Aged↗
PubMed1992

Re-emergence in remission of primary clone in acute myelogenous leukaemias with multiple chromosomal aberrations at diagnosis.

We describe the clinical, haematological and cytogenetic features of three patients who had acute myelogenous leukaemia (AML) with complex bone marrow karyotypes when first cytogenetically examined. Induction chemotherapy led to remission from the acute leukaemia. However, neither clinically nor morphologically did this remission mean a return to normal haematopoiesis. The two patients who displayed myelodysplastic features before and when AML was diagnosed, again developed myelodysplasia, and the third patient, who had a long history of polycythaemia vera, returned to this myeloproliferative condition. Nor was cytogenetic normalization achieved; instead, abnormal cell clones were found in which all but one of the karyotypic aberrations present at acute leukaemia diagnosis had disappeared. The solitary anomalies that were detected in these reemerging clones must correspond to the primary cytogenetic aberrations of the patients pre-leukaemic diseases. They were del(5) (q11q33) and del(17) (p11) in the two myelodysplastic cases, and der(18)t(9;18) (p11;p11) in the patient with long-standing polycythaemia vera. The other, secondary, aberrations were probably the leukaemogenic changes, and with the eradication or reduction of the subclones containing them, the leukaemic phenotype disappeared. The three cases add cytogenetic evidence to the growing understanding that the remission obtained in some AMLs is actually a return to a preleukaemic, myeloproliferative or myelodysplastic, syndrome.

Adult↗
PubMed1991

Prognostic importance of flow cytometric immunophenotyping of 540 consecutive patients with B-cell chronic lymphocytic leukemia.

Blood mononuclear cells from 540 newly diagnosed, unselected patients with B-cell chronic lymphocytic leukemia (CLL) were examined by immunofluorescence flow cytometry for a panel of surface membrane markers, including IgM and IgD, the monoclonal antibodies anti-CD3, -5, -20, -21, -22, -FMC7, and, for the final 125 patients, anti-CD23. There were 503 CD5+ and 37 CD5- cases. In the CD5+ cases, the cells typically expressed IgM, IgD, CD20, CD21, CD22, and CD23. In univariate analysis, age, clinical stage, IgM-fluorescence intensity, CD23, and FMC7 had significant prognostic importance, with high IgM-fluorescence intensity, high FMC7, and low CD23 expression being associated with a short survival. There was no significant difference in survival between 351 cases expressing IgMD and 55 cases expressing IgM without IgD, or between kappa and lambda light chain monoclonal cases. CD20, CD21, and CD22 had no prognostic importance. In Cox multiple regression analyses, age, CD23, IgM-fluorescence intensity, and clinical stage (International Workshop System) had independent prognostic importance. Thus, besides clinical variables, CD23 and IgM intensity might be useful prognostic markers in the management of CD5+, B-cell CLL. The survival of CD5- patients was on the borderline of being significantly shorter than that of CD5+ patients. The majority of the CD5- cases were FMC7+, CD23-, had strong IgM fluorescence, and had splenomegaly.

Aged↗
PubMed1991

[Malignant hematologic diseases. Diagnosis and treatment. A clearing report].

The malignant haematological disorders comprise the main groups leukemia, malignant lymphoma and multiple myeloma and the potentially malignant disorders: myelodysplastic syndrome, polycythaemia vera, myelofibrosis and M-component of uncertain significance. The common feature of all these disorders is monoclonality, i.e. they originate from one single cell. Around 2,000 new cases are diagnosed per year in Denmark. Because of the relative small number of patients, complex diagnosis and treatment (especially the possibility of cure on intensive treatment) a high degree of centralization is warranted to secure an evenly distributed high level of patient care and research. The present rules for referral of patients are unsatisfactory. A new referral system is proposed based on a common set of rules, agreed upon by five haematological centers in Denmark and the surrounding region, comprising diagnostic procedures, treatment, research and development for all haematological patients in the area. Based on these common rules (functional centralization) it is decided whether the individual patient can be treated in the primary hospital or should be referred to a center (geographical centralization). Recommendations about diagnosis, treatment and referral are made in this report. Detailed suggestions are given for diseases which may be treated locally whereas no detailed regimens are given for diseases and disease stages which should be centralized. In the latter cases, the main emphasis is placed on a presentation of treatment results.

Denmark↗
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

Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas. Danish LYFO Study Group.

In a Danish population-based non-Hodgkin lymphoma (NHL) registry, 1257 newly diagnosed NHL cases were registered over a 5-year period. Of these, 463 (37%) were extranodal. The gastrointestinal tract was the most common site of extranodal involvement (30% of the cases). Histologically, 44% of all extranodal NHL cases had high-grade, 17% intermediate and 27% low-grade features, while 12% were unclassified. The most common histological subtype (Kiel) was the centroblastic diffuse (23% of cases). 50% of all extranodal NHL were localised (stage IE or IIE) and 27% had B symptoms. Site-specific features included a strong age-correlation for thyroid and testes lymphoma (greater than 50 years) and a high prevalence of female cases in thyroid and salivary glands lymphomas (M/F 0.14 and 0.30, respectively). Overall 7-year survival for extranodal NHL was 46% (median 4.9 years). Poor prognosis patients could be identified by the presence of one or more of the following presentation characteristics: age greater than 65 years, B symptoms, high-grade histology, disseminated disease, elevated s-IgA and hyperuricaemia. Relative risk values ranged from 2.1 for age and B symptoms to 1.7 for hyperuricaemia.

Adolescent↗
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

Tumor cell concentration and tumor burden in relation to histopathologic subtype and other prognostic factors in early stage Hodgkin's disease. The Danish National Hodgkin Study Group.

Prognostic factors were examined by multivariate analysis after a recent follow-up of the 300 patients with Hodgkin's disease pathologic stage (PS) I or II treated with radiotherapy +/- adjuvant combination chemotherapy in the prospective randomized trial of the Danish National Hodgkin Study. Initial biopsy material was classified according to the Rye histopathologic classification, the grading and subclassification proposed by the British National Lymphoma Investigation (BNLI), and tumor cell concentration in sections. Tumor cell concentration as a prognostic factor turned out to be better than the other classifications. However, if macroscopic tumor burden was taken into account both tumor cell concentration and the other histopathologic classification systems lost their prognostic significance. Significantly, however, a combination of macroscopic tumor burden and tumor cell concentration, yielding an estimate of the total tumor cell burden, was even better than the macroscopic tumor burden as a prognostic factor. In conclusion, a simple tumor cell concentration count seems to be the most useful form of histopathologic subtyping for prognostic purposes in early stage Hodgkin's disease.

Hodgkin Disease↗
PubMed1990

Long-term survival and late relapses in acute leukaemia in adults.

34 out of 403 apparently unselected adult patients with acute leukaemia referred to a single department from 1970 through 1989 survived more than 3 years. The cumulative rate of relapse after 3 years was 39% in patients with acute myeloblastic leukaemia (AML) and 74% in patients with acute lymphoblastic leukaemia (ALL). The latest relapse was observed 75 months after diagnosis in AML and 98 months after diagnosis in ALL. 65% of the long-term survivors were able to undertake normal physical activity, 26% had decreased activity, and 9% were unable to work. 5-year survival for all patients, whether treated or not, during two successive decades was 16% versus 18% and 5% versus 6%, respectively, for ALL and AML. The departmental results were identical with population-based national results. Only in patients 15-49 years of age with AML was there evidence that more intensive treatment had led to better survival.

Adolescent↗
PubMed1990

Phase III trial of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) versus cisplatin, etoposide, bleomycin and prednisone (CisEBP) for the treatment of advanced non-Hodgkin's lymphoma of high grade malignancy. The Danish Lymphoma Study Group.

The trial included 85 previously untreated patients (median age 61 years) with stage III or IV non-Hodgkin's lymphoma (NHL) of the subtypes centrocytic lymphoma, diffuse centroblastic lymphoma, immunocytoma, immunoblastic lymphoma, or unclassified lymphoma of high grade malignancy. The patients were randomized to 9 monthly treatment cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CisEBP (cisplatin, bleomycin, etoposide, prednisone). Patients who had failed to achieve even a partial response (PR) after the completion of 2 cycles were switched to the alternative regimen. Complete response (CR) on primary treatment was obtained in 70% (55-83%) of CHOP-treated patients and in 25% (13-41%) of CisEBP-treated patients (p = 0.0004). Secondary CHOP treatment produced CR in 7 (30%) of 24 patients and secondary CisEBP treatment led to CR in 2 (15%) of 14 patients. The median survival was 3.4 years in the CHOP arm and 2.6 years in the CisEBP arm (p = 0.78). Hematologic toxicity was mainly leukocytopenia and anemia in both treatment arms. Non-hematological toxicity was slight, and late toxicity was insignificant. Three treatment-related deaths were noted. We conclude that CHOP induces more remissions than CisEBP in advanced lymphomas of high grade malignancy.

Adult↗
PubMed1989

Long-term storage of xanthan in seawater at elevated temperature: physical dimensions and chemical composition of degradation products.

Commercial xanthan and xanthan from Xanthomonas strain 646 produced in the laboratory have been subjected to heat treatment for various periods of time in oxygen depleted, high salinity, aqueous solutions. Both the viscosity and the carbohydrate content decreased with increasing incubation time at a specified temperature. The losses increased with increasing temperature. Data from electron micrographs and dialysable sugar content indicate that random cleavage of the double-stranded xanthan chain is the main mechanism responsible for the decreasing viscosity. Removal of pyruvate and acetate substituents on the side chains was apparently not related to the change in physical dimensions. The mannose/glucose ratio in the non-diffusible fraction decreased with incubation time, apparently not related to change in physical dimensions. Electron micrographs showed that one of the samples appeared as highly aggregated in the native condition. After 1 month at 80 degrees C, we observed that the aggregates had dissolved and that the viscosity had increased fivefold. This suggests that heat treatment can be used to avoid microgels and to obtain higher viscosifying power of the native xanthan.

Carbohydrates↗
PubMed1988

CHOP versus prednisolone + chlorambucil in chronic lymphocytic leukemia (CLL): preliminary results of a randomized multicenter study.

Five hundred and fifty consecutive patients with newly diagnosed B-CLL have been registered and classified in a Danish multicenter study. The study includes a protocol for primary treatment of patients in stage B or C (at diagnosis or after demonstrated progression), below 76 years of age, and without complicating serious disease. Until now 144 such patients have been randomized to either prednisolone (PRD) plus chlorambucil (CLB) 5 days every 4 weeks or monthly intensive CHOP treatment. Twenty-nine percent of the treated patients achieved CR on PRD + CLB versus 63% on CHOP (p less than 0.005). No response was found in 29% versus 18%, respectively (NS). A significant difference in survival between patients achieving CR, PR and NR was also demonstrated, whereas to date no difference in survival could be demonstrated between the two regimens. The toxicity was limited, and only 2 treatment-related deaths occurred in approximately 700 CHOP treatment series.

Adult↗
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↗
PubMed1979

The effect of acetyl salicylic acid and dipyridamole on thromboembolic complications in splenectomized patients with myelofibrosis.

The effect of combined treatment with acetyl salicylic acid and dipyridamole on thrombic phenomena was studied in splenectomized patients with an aggressive form of myelofibrosis. 3 of these patients had thrombotic episodes, shortened platelet survival and an abnormal platelet aggregation pattern. The treatment with antiplatelet drugs resulted in a decreased platelet utilization as evidenced by clinical improvement and an increasing platelet concentration.

Aged↗
PubMed1978

Traffic of T and B lymphocytes in the normal spleen.

The occurrence of C3b and C3d complement receptors and of Fc and E receptors in normal splenic tissue was studied in cryostat sections incubated with specific marker cells. Thereby the topographic distribution of T and B lymphocytes in the splenic tissue was mapped: Te lymphocytes are found especially in the periateriolar sheaths, B lymphocytes in eccentric zones around the arterioles. The cells in the splenic pulp carry especially Fc, but also C3b receptors, whereas C3d receptors appear to be specific of lymphocytes. The basic lymphocyte traffic behind the mapped distribution of the lymphocyte subpopulations in the spleen was elucidated by lymphocyte kinetic studies using autologous 51Cr-labelled reinfused lymphocytes. These studies were performed partly on normal persons and partly on splenectomized persons without immune defects. The results indicate the presence of an exchangeable pool of T as well as of B lymphocytes in the spleen, the T cell pool being larger and making up in normals about 30% of the total exchangeable T lymphocyte mass. The matrix for the T lymphocyte pool in the spleen is the periateriolar sheaths. The difference in structure between the lymph nodes and the lymphoid tissue of the spleen, including differences in the distribution of lymphocyte subpopulations, are explained by the special vascular arrangement in the spleen.

Adult↗