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Biomedical subjects

M M Hansen

Publications and source records attributed to M M Hansen.

At least 55 records · Page 3Linked to original sources
PubMed1992

Mitoxantrone in the treatment of chronic lymphocytic leukemia.

During the last few years it has been shown that intensive or continuing chemotherapy of patients with advanced chronic lymphocytic leukemia prolongs survival. In the search for new effective drugs with tolerable toxicity, mitoxantrone was evaluated in this phase 2 study. Seven of 11 previously untreated patients achieved complete or partial remission after single agent treatment with mitoxantrone, and 5 of .16 previously treated patients had the same degree of response. Only minor toxicity was observed. Therefore, it appears likely that mitoxantrone is as effective as chlorambucil, and it would seem justified to evaluate mitoxantrone in future combination chemotherapy regimens in patients with advanced chronic lymphocytic leukemia.

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

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

Refractory myelomatosis treated with mitoxantrone in combination with vincristine and prednisone (NOP-regimen): a phase II study. The Nordic Myeloma Study Group (NMSG)

In a phase II study, patients with refractory myelomatosis were treated with a combination chemotherapy (NOP regimen): mitoxantrone (bolus injection of 4 mg/m2 on days 1-4), vincristine (continuous infusion of 0.4 mg/24 h on days 1-4) and prednisone (250 mg/d on days 1-4 and 17-20). The treatment was repeated every 4 weeks. Ninety-two patients were treated after they were found refractory to treatment with melphalan and prednisone (and occasionally vincristine) (n = 50) or more intensive treatment regimens (n = 42) including anthracyclines (n = 18). Response (greater than or equal to 50% reduction of M protein) was obtained in 23 patients and minor response (clinical improvement but less than 50% reduction in M protein) in 22 patients. The median duration of the response was 7.5 months. Equal response rates were observed irrespective of the type of previous treatment. The major toxicity was myelosuppression with severe granulocytopenia and infections. However, the frequency decreased throughout the cycles. The NOP treatment is recommended in refractory myelomatosis, especially in patients refractory to other intensive regimens. Patients in a poor clinical condition or with thrombocytopenia before treatment should have a reduced mitoxantrone dose in the first treatment cycles.

Adult↗
PubMed1990

Organic mercury in Greenland birds and mammals.

Muscle, liver and kidney samples of 20 species of birds, seals, whales and polar bear were analyzed for total and organic mercury. Organic mercury concentrations varied considerably between individuals. A general tendency towards age accumulation was found, together with log-linear correlations between organic mercury concentrations in the three tissues. The major part of the muscle mercury was organic (maximum concentration found was 1235 micrograms kg-1 wet wt). This also applied to liver of birds, while in mammal liver organic mercury concentrations approached a level of 2000 micrograms kg-1 wet wt, which was not exceeded even when the total mercury concentration was greater than 100,000 micrograms kg-1 wet wt. The percentage of organic mercury in relation to total mercury in kidney of seals and whales was 10-20% (maximum 982 micrograms organic mercury kg-1 wet wt), while in polar bear it was less than 6% (maximum 217 micrograms kg-1 wet wt). For the monitoring of local food in the Arctic, the simpler and less expensive analysis of total mercury suffices when testing muscle, whereas liver and kidney should be tested for organic mercury as well.

Animals↗
PubMed1989

B-cell chronic lymphocytic leukaemia: clonal chromosome abnormalities and prognosis in 89 cases.

The results of cytogenetic studies are reported in 89 patients with B-cell CLL. LPS (E. coli lipopolysaccharide), PWM (pokeweed mitogen), PHA (phytohaemagglutinin), EBV (Epstein-Barr virus), TPA (phorbol 12-myristate 13-acetate), and LA (leucoagglutinin) were used as mitogens. Mitoses were obtained from 78 cases. Clonal aberrations could be demonstrated in 26 cases. Trisomy 12 was the most frequent finding (8 cases) and was sole abnormality in 4 cases. Chromosomes #14, #17, and #11 were involved in structural aberrations in 5, 7, and 7 cases respectively, but a t(11;14)(q13;q32) was the only structural aberration seen more than once. The median observation time was 47 months (range 1-87). The presence of clonal abnormalities did not influence survival significantly, either when calculated from diagnosis or from cytogenetic analysis. Patients with more than one aberration, however, had a significantly shorter survival than patients with normal mitoses only (p less than 0.05). The survival of 8 patients with trisomy 12 (in 4 as sole abnormality) was not different from that of patients with normal mitoses only.

Chromosome Aberrations↗
PubMed1988

Carcinoma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin's lymphoma.

We observed nine cases of transitional-cell carcinoma of the urinary bladder among patients who had had long-term treatment of other cancers with cyclophosphamide. Seven of the bladder carcinomas occurred within a cohort of 471 patients treated for non-Hodgkin's lymphomas. In this cohort the relative risk of bladder cancer was 6.8 (95 percent confidence interval, 3.2 to 14.2). The cumulative risk (mean +/- SE) was 3.5 +/- 1.8 percent 8 years after the start of treatment with cyclophosphamide and 10.7 +/- 4.9 percent after 12 years. Three of the nine patients were 50 years of age or younger; seven died with progressive bladder cancer. Subsequently, an additional patient had acute nonlymphocytic leukemia. Hemorrhagic cystitis was observed in 33 patients (cumulative risk, 11.8 +/- 2.1 percent after five years). Development of carcinoma of the urinary bladder was not related to previous hemorrhagic cystitis. The results caution against long-term treatment with cyclophosphamide for diseases with a favorable prognosis.

Adult↗
PubMed1988

High activity of mitoxantrone in previously untreated low-grade lymphomas.

A consecutive series of 21 previously untreated patients with low-grade non-Hodgkin lymphomas were treated with mitoxantrone 5 mg/m2 daily for 3 days every 3 weeks. The cumulative dose did not exceed 165 mg/m2 in any patient. In this group, 7 patients had small lymphocytic lymphomas, 10 patients had follicular small cleaved cell lymphomas, and 4 patients had follicular mixed small- and large-cell lymphomas. Of the 21 patients, 20 obtained remission (complete in 6, partial in 14), and 15 of these are still in remission. Relapse-free survival is 68% at 2 years. None of the patients has died. Nonhematologic toxicity was modest. No severe alopecia was seen, and only 6 patients had nausea and vomiting (WHO grade 1-3). No cardiac toxicity was seen. In conclusion, mitoxantrone is a highly active and well-tolerated drug in this subset of patients. Hematologic toxicity, especially leukopenia, was dose limiting, and a reduction of the dose was necessary in 15 out of the 21 patients.

Adult↗
PubMed1988

Refractoriness to alpha-interferon (Intron A) in previously chemotherapy-treated patients with chronic myelocytic leukaemia.

8 patients with chronic myeloid leukaemia in the chronic phase who had previously received chemotherapy were given alpha-interferon (Intron A). The Intron A was administered subcutaneously at a dose of 2 x 10(6) I.U./m2 three times a week and this was increased to 4-5 million I.U./m2 daily if no response was obtained after 6-8 months. 1 patient was Philadelphia chromosome-negative and was the only one who showed a major response to treatment. The other 7 patients never achieved haematologic remissions, or even a significant reduction in the immature blood leucocyte count or spleen size.

Adult↗
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↗
PubMed1987

Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy.

391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t-ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk of t-ANLL. The hazard rate of t-ANLL was roughly proportional to the square of patient age and to the total cumulative dose of alkylating agents. In 320 patients treated with alkylating agents the cumulative risk of t-ANLL increased steadily from 1 year after the start of treatment and reached 13.0% (SE 3.0) at 10 years after which time there were no further cases. Calculated from cessation of therapy with alkylating agents, however, the cumulative risk curve increased steeply during the first 1-2 years then gradually levelled out and no new cases were observed beyond 7 years. With a 15-year follow-up the general risk of solid tumours was not increased.

Adult↗
PubMed1987

Lack of prognostic significance of T-lymphocyte subset counts in B-cell chronic lymphocytic leukaemia.

In the 50 newly diagnosed, unselected, untreated B-CLL patients, the absolute numbers of blood T cells, T-helper cells, and T-suppressor/cytotoxic cells were by flow cytometric counting of mononuclear cells labelled with the monoclonal antibodies Leu5 (T cells), Leu3a (T-helper cells), and Leu2a (T-suppressor/cytotoxic cells). These estimations and the serum concentrations of IgG, IgA, and IgM were correlated to clinical stage (International Workshop System) and pretreatment observation time. For all patients together, the mean counts of Leu5+, Leu3+, and Leu2+ cells were significantly increased compared with the mean counts in 12 healthy controls (Mann-Whitney). In patients with advanced disease (stage B + C), both T-subset mean cell counts were significantly increased, whereas in patients with early-stage disease (stage A), although some high T-helper cell counts were noted, only the T-suppressor/cytotoxic mean cell count increase reached significance. Thus a trend was observed of a more frequent T-suppressor/cytotoxic cell predominance in early-stage disease, which is the opposite of the findings in most other prognostic studies. However, there was no significant difference in pre-treatment observation time according to T-helper: T-suppressor cell ratio below vs. above 1.0, irrespective of stage, whereas according to clinical stage, the pretreatment observation time in stage A was highly significantly longer than in stage B + C (logrank test). Thus, no independent prognostic significance of T-subset counts was found as judged by pretreatment observation time. No correlation was found between the occurrence of hypogammaglobulinaemia, T-subset ratios or T-subset counts.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗