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Biomedical subjects

B Simonsson

Publications and source records attributed to B Simonsson.

At least 73 records · Page 4Linked to original sources
PubMed1989

T-cell activation and subset patterns are altered in B-CLL and correlate with the stage of the disease.

Two-color FACS analysis was used to study activated and "functional" T and natural killer (NK) cell subsets of circulating lymphocytes in 23 patients with B-type chronic lymphocytic leukemia (B-CLL) and in 30 healthy subjects. As compared with controls, B-CLL patients had increased absolute numbers of phenotypically activated, HLA-DR+ CD4+ and CD8+ cells and T suppressor/effector (CD11b+CD8+) cells. When patients in Rai stages II through IV (n = 11) were compared with cases in Rai stages O through I (n = 12), the former group of patients had higher numbers of activated CD4+ and CD8+ T cells and decreased levels of suppressor/effector T cells. The absolute numbers of T suppressor/inducer (CD45R+CD4+) cells were elevated in patients with stage O through I disease but within normal range in stage II through IV leukemia. We further showed that the absolute numbers of NK-like (CD16+) cells and their activated counterparts (DR+CD16+) are elevated in B-CLL patients as compared with healthy subjects. The comparison of relative T and NK subsets in the blood of patients and controls showed that the proportions of CD4+, CD8+, and CD16+ cells expressing the activation marker HLA-DR were increased in B-CLL. Furthermore, the percentage of T-suppressor/inducer (CD45R+) cells within the CD4+ population was decreased in the patients. The proportion of T-suppressor/effector (CD11b+) cells within the CD8+ subset was reduced in subjects with stage II-IV disease only. When stimulated in vitro with the T-cell-dependent inducer TPA, B-CLL cells from patients in Rai stages II through IV secreted larger amounts of IgM as compared with cells from stage O through I patients. A positive correlation was observed between the degree of phenotypic activation of CD4+ T-helper cells and their functional capacity to augment IgM secretion by autologous B-CLL cells. Our findings indicate a tumor cell-directed regulatory role of T cells (and possibly NK cells as well) in B-CLL. Furthermore, monitoring of phenotypically activated and functional T-cell subsets may be helpful in the prediction of disease progression and timing of therapy in B-CLL.

Antigen-Presenting Cells↗
PubMed1989

Pharmacokinetic and metabolic studies of high-dose busulphan in adults.

The pharmacokinetics of high-dose busulphan was studied in adult patients with acute myeloblastic leukaemia after oral doses of 1 mg.kg-1 every 6 h for 4 days. The mean steady-state plasma concentration was 1080 ng/ml-1 during the treatment. Individual steady-state concentrations after the last dose on average were 32% lower than those predicted from total AUC measurements following the first dose. Mean elimination half-life in plasma was 2.3 h after the last dose and 3.4 h after the first dose which suggests that busulfan may increase its own metabolic rate on repeated treatment. The cerebrospinal fluid/plasma concentration ratio of busulphan was 1.3. Busulphan showed insignificant protein binding in plasma (7.4%). About 2% of the dose was excreted unchanged in the urine. For the first time sulpholane, 3-hydroxysulpholane and tetrahydrothiophene 1-oxide were identified as urinary metabolites of busulphan in man.

Adult↗
PubMed1989

B lymphocyte regeneration in marrow and blood after autologous bone marrow transplantation: increased numbers of B cells carrying activation and progression markers.

The reconstitution of B cells in the bone marrow and peripheral blood was prospectively studied in 27 patients undergoing autologous bone marrow transplantation (ABMT). No major differences in B cell regeneration patterns were recorded between patients receiving marrows purged of B cells (anti-CD10 + 19; n = 17) and patients receiving unpurged marrows (n = 10). Compared with healthy controls, elevated absolute and relative numbers of B cells were recorded in the blood and marrow at +6 and +12 months in both groups of patients. CD23+ B cells were severely depressed during the first three months post ABMT, indicating immaturity. A twofold increase in B cells carrying the activation marker 4F2 was recorded in the marrow at +1 month. Serum immunoglobulin levels (IgG, IgA, IgM) were within low-normal range throughout the study. The depressed B cell responses reported after allogeneic and autologous BMT could in part be explained by the low expression of the CD23 antigen on B cells after such therapy.

Antigens, CD19↗
PubMed1989

Marked erythropoietin increase before fall in Hb after treatment with cytostatic drugs suggests mechanism other than anaemia for stimulation.

Serum erythropoietin (Epo) was measured in 23 patients before, during and after intensive cytostatic treatment courses for acute leukaemia or before bone marrow transplantation. A marked increase was seen in all patients, starting 1 or 2 d after initiation of treatment. A peak was reached after about 7 d, at levels as high as 1450 IU/l, after which Epo fell rapidly, even in patients who were anaemic at that time. In 13 of the patients there was no fall in Hb level that could explain the increase in Epo. The increase was too large to be explained by an altered Epo metabolism or marrow utilization. Cytostatic drugs cause an increase in Epo production not mediated through anaemia, possibly initiated by a cytostatic effect on the kidneys or by an unknown stimulatory factor, responsive to bone marrow inhibition.

Antineoplastic Agents↗
PubMed1989

Acute lymphoblastic leukaemia in adults in Sweden 1977-84: a retrospective analysis. Swedish ALL-Group.

The present study is a retrospective analysis of the outcome in 210 patients diagnosed and treated as having acute lymphoblastic leukaemia (ALL) in Sweden during 1977-84. 131 patients were morphologically rediagnosed as ALL. For the ALL-patients, nine different remission induction regimens were used. Remission frequency was 69%, without statistical difference according to induction treatment. However, the reasons for remission failure differed among therapy groups. The number of responders was significantly higher among patients who received a remission induction therapy with an anthracycline and/or L-asparaginase. Maintenance therapy consisted in most cases of 6-mercaptopurine and methotrexate with reinduction courses for 2-3 years. Median survival time was 13 months and median duration of first remission (MRD) 11 months. For a subgroup of patients (n = 29) treated with the most intense remission induction regimens, including at least 4 cytostatic drugs with both an anthracyclilne and L-asparaginase, the MRD is not yet reached, the shortest follow up time is 43 + months, and the probability of remaining in complete remission is 66%. We conclude that aggressive cytostatic therapy, with induction regimens including both an anthracycline and L-asparaginase, may cure a considerable number of adult ALL-patients.

Adolescent↗
PubMed1989

Treatment of pure red-cell aplasia and aplastic anaemia with ciclosporin: long-term clinical effects.

6 patients with pure red-cell aplasia were treated with Ciclosporin (Cyclosporine A; CS) alone or combined with prednisolone for a period of 9-46 (median 27) months. Prior to study, 5 cases had refractory disease, steroids were contraindicated in 1, and 4/6 patients, including 2 cases with congenital disease, had a disease duration exceeding 11 years. A complete haematological response was obtained in 5/6 subjects, and a partial response in 1. When the pre-treatment Hb levels (mean +/- S.D. = 64 +/- 13 g/l, range 41-80) for all 6 PRCA patients were compared with the Hb levels after 6 months of CS therapy (104 +/- 17 g/l, 80-125), a significant improvement was registered (p less than 0.005). In half of the patients, remission is maintained with CS as single drug in a dose-dependent manner. We also treated 5 patients with refractory severe aplastic anaemia with CS (1 case) or CS plus prednisolone (4 cases) for 3-27 (median 10) months. Only 1 patient responded. In this case, a complete haematological remission was induced with CS alone, and remission has been maintained for 27 months. Side effects of CS therapy were common but were dose-dependent and reversible, with the exception of persistent nephrotoxicity in 1 patient with pure red-cell aplasia. Based on our present results and a survey of the literature, we conclude that CS therapy is effective and indicated in refractory pure red-cell aplasia. In severe aplastic anaemia resistant to conventional immunosuppression, the response rate is lower, but a small proportion (around 15%) of patients may benefit from CS therapy. Longer treatment periods may, however, be needed to evaluate the role of CS in aplastic anaemia.

Adult↗
PubMed1989

B-cell reconstitution after autologous bone marrow transplantation: increase in serum CD23 ("IgE-binding factor") precedes IgE and B-cell regeneration.

The serum levels of IgE and the soluble cleavage product of CD23 (sCD23) were prospectively monitored for up to 1 year after transplantation in 34 patients who underwent autologous (n = 33) or syngeneic (n = 1) bone marrow transplantation (BMT). In 25 patients (74%), a transient IgE peak (two- to 2,750-fold increase) appeared in the serum 3 to 4 weeks after BMT. In 18 patients (51%), a two- to 125-fold increase in sCD23 coincided with the IgE peak. In only three patients was a sCD23 peak observed without a concomitant increase in IgE. The sCD23 increment preceded the IgE peak in each individual case. During the period of increased sCD23 serum levels, the absolute numbers of circulating B cells and other cell types expressing surface CD23 were extremely low. The biologic significance of these findings is discussed in light of present knowledge of regulation of B-cell growth and differentiation with special reference to the role of sCD23 as a multifunctional cytokine.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Regeneration of functional and activated NK and T sub-subset cells in the marrow and blood after autologous bone marrow transplantation: a prospective phenotypic study with 2/3-color FACS analysis.

The phenotypic reconstitution of lymphoid cells in the bone marrow and peripheral blood was examined prospectively in 27 patients who underwent autologous bone marrow transplantation (ABMT) for leukemia/lymphoma. Patterns of activation within NK and T cell subsets as well as T sub-subsets were studied with monoclonal antibodies in two- and three-color FACS analysis. NK-like cells (CD16+) were found to be increased in the peripheral blood and bone marrow after ABMT. The expression of two activation markers, 4F2 and HLA-DR, was sustainedly increased within this subset. High numbers of CD4+ and CD8+ T cells carrying surface HLA-DR were found early after ABMT both in blood and marrow. The T suppressor inducer cell sub-subset (CD45R+ CD4+) was severely depressed in both the blood and marrow 6-9 months post-ABMT. Using three-color FACS analysis, half of this T sub-subset was shown to express HLA-DR+. The levels of T suppressor effector-like cells (CD11+ CD8+) remained within the normal range in both peripheral blood and bone marrow during follow-up. The HLA-DR expression was elevated and equally distributed between the CD11- CD8+ and CD11+ CD8+ sub-subset cells. There was no major impact of marrow T cell purging or CMV carrier status on the phenotypic NK/T cell reconstitution. The present results provide an immune phenotypic basis for the suggested generation of anti-leukemic NK-like and T suppressor-like activity after ABMT.

Adolescent↗
PubMed1989

Cerebrospinal fluid and plasma concentrations of busulfan during high-dose therapy.

A patient with acute myeloblastic leukemia received high-dose busulfan (1 mg/kg by mouth every 6 h for 4 days) as myelo-ablative therapy for autologous bone marrow transplantation. Rapid entry of busulfan into the cerebrospinal fluid (CSF) was observed. Plasma and CSF concentrations of busulfan were comparable during the 4 days of treatment. The elimination half-lives of busulfan in plasma and CSF were 2.6 h and 2.8 h respectively during the first 12 h after the last dose.

Bone Marrow Transplantation↗
PubMed1989

Autologous bone marrow transplantation with monoclonal antibody purged marrow for high risk acute lymphoblastic leukemia.

Fifty-four patients with acute lymphoblastic leukemia (ALL: 1 relapse, 21 high risk first complete remission (CR 1), 29 second CR (CR 2), and 3 third CR (CR 3) were treated by autologous bone marrow transplantation at three centers. Before storage, the marrows were purged ex vivo with appropriate MAbs RFAL3 (CD10), SB4 (CD19), and RFT2 (CD7), with rabbit serum as the source of complement. All patients received total body irradiation either 750 cGy (middose 15 cGy/min) as a single fraction or 6 x 200 cGy over 3 days (midline dose 16 cGy/min) with lung shielding from 1,100 cGy. The patients who received 750 cGy also received cyclophosphamide or the same drug combined with ara-C or prednisone, teniposide, vincristine, ara-C, and dauno-rubicin. Patients receiving 200 cGy x 6 also received either cyclophosphamide, melphalan, or ara-C and cyclophosphamide. Three patients died of post transplantation complications (interstitial pneumonia, hepatitis B liver necrosis, or encephalitis). This gives a procedure related mortality of 5%. Nonfatal complications were 10 cases of septicemia, 4 interstitial pneumonia, 2 interstitial nephritis, 1 veno-occlusive disease (VOD), and 1 case of hemolytic uremic syndrome. The patient autografted in relapse died of relapse within 2 months. In CR 1 6 or 21 patients have had a relapse, and the actuarial leukemia free survival from CR is 65% (median follow-up 16 months). In CR 2-3 18 of 32 patients have relapsed, and the actuarial leukemia free survival is 31% (median follow-up 18.5 months) from CR. Twelve patients have achieved an inversion, (i.e., present CR longer than previous CR), with a further seven with the potential to achieve inversion. We conclude that ABMT in high risk ALL has a low procedure related mortality (5%), and there are few other complications. The in vitro purging with MAbs had no adverse effect on bone marrow reconstitution, but this study was not designed to demonstrate its antileukemic efficacy. The actuarial leukemia free survival time in the present study for patients with high risk CR 1 and the inversions in CF 2-3 are promising and indicate a potential beneficial effect of ABMT.

Antibodies, Monoclonal↗
PubMed1989

Lung mechanics and their relationship to lung volumes in pulmonary sarcoidosis.

Pulmonary sarcoidosis was studied with respect to lung mechanical properties and to the influence of these on lung volumes. Sixty-six patients, with histological support for the diagnosis of sarcoidosis, and radiological signs of pulmonary involvement, i.e., stage II or III, were studied. The static pressure/volume (P/V) curves showed that the static elastic recoil pressure (PelL) tended to be increased at a given percentage of predicted total lung capacity (TLC). Reduction of static lung compliance (CstL) was a typical finding. At maximal inspiration PelL was abnormally low in 20 subjects, including in the main those with recent onset of the disease and older patients. The possibility of a greater inflammatory activity at the site of mechanical receptors in the lungs and airways of these patients is proposed. Pulmonary resistance, measured at a given PelL, was usually increased signifying bronchial involvement. TLC, residual volume (RV) and functional residual capacity (FRC) were lower in current smokers and ex-smokers than in lifelong nonsmokers. This may be due to synergistic effects of the inflammatory processes caused by smoking and sarcoidosis. A reduced vital capacity (VC) mainly reflected a low CstL but also obstruction with increased RV. Forced expiratory volume in one second (FEV1) reflected lung stiffness and obstruction equally. Lung mechanics revealed functional abnormalities which were not obvious from the standard tests, particularly in patients with respiratory symptoms.

Adult↗
PubMed1988

Inter- and intraindividual differences in oral chlorambucil pharmacokinetics.

Inter- and intraindividual variation in the pharmacokinetics of oral chlorambucil was investigated in patients with chronic lymphocytic leukaemia. Five patients were given in randomized order 15, 40, 60 and 70 mg chlorambucil p.o. and plasma was analyzed for chlorambucil and its cytotoxic metabolite phenyl acetic acid mustard. The area under the plasma concentration-time curve of chlorambucil varied two- to fourfold between patients at each dose level. The AUC of the metabolite was higher and showed twofold interindividual variation. The intraindividual dose-corrected AUCcs also varied twofold. No dose dependency of the dose corrected AUC was seen either for chlorambucil or the metabolite. Elimination of both compounds form plasma was rapid, with half-lives of 1.01 and 1.94, respectively.

Administration, Oral↗
PubMed1988

Biochemical markers in multiple myeloma: a multivariate analysis.

The analysis of individual biochemical and clinical variables in 121 patients with multiple myeloma showed that serum beta 2-microglobulin (S-beta 2m) had the most significant relation to survival. Other variables such as serum thymidine kinase (S-TK), serum lactate dehydrogenase (S-LDH), S-creatinine, haemoglobin (Hb), ESR, S-albumin, age and clinical stage were also significant. No such relationship was found with M-component, presence of light chains in urine, type of secreted immunoglobulin or S-calcium. The exclusion of clinical stage in the first multivariate analysis resulted in a model consisting of S-beta 2m, age and S-TK, none of the other variables gave additional information. When in the second multivariate analysis the basic variables involved in staging procedure were excluded and clinical stage included, stage III, but not stage II, was found to give additional information to the model described above. Individual analysis of the variables showed that Hb had the most significant relation to effect of initial therapy. Other significant variables were S-TK, S-beta 2m and age. When using the multivariate approach, Hb alone was found to contain all the relevant information.

Adult↗
PubMed1988

Aggressive treatment improves survival in adult acute lymphoblastic leukemia.

20 consecutive adult patients with acute lymphoblastic leukemia were treated with an intense induction regimen including vincristine, doxorubicin, prednisolone, L-asparaginase and cyclophosphamide. 16 patients (80%) achieved complete remission and were then given CNS prophylaxis and 3 years of maintenance therapy. With minimum follow-up of 24 months, the median duration of first remission is 37+ months. Out of 10 patients who have completed maintenance therapy, 2 have relapsed after 14 and 22 months, respectively, and 7 are in continuous complete remission 1+-55+ months off therapy.

Adolescent↗
PubMed1988

Autologous bone marrow transplantation in acute lymphoblastic leukemia--preclinical immunologic studies.

Immunologic aspects of autologous bone marrow transplantation (ABMT), immunodiagnosis, patient monitoring, and the purging of bone marrow have been studied in individual patients. It was demonstrated that the most sensitive method for detecting lymphoid cells which show the phenotypes of ALLs of B or T lineage was double immunofluorescence staining for nuclear terminal transferase (TdT) and B or T lineage antigens. With the help of these sensitive tests in the presence of rabbit complement (C'), MAbs CD10 (RFAL3 of IgM class), CD19 (SB4 of IgM class), and their cocktail were capable of eliminating greater than 3 log blast cells of B lineage ALL in 84%, 75.5%, and 90% of cases, respectively. The same reagents lysed 26.8%, 0%, and 45% of blasts in the presence of human C'. CD7 (RFT2, IgG2) eliminated greater than 3 log T-ALL blast cells in 73% of cases. The proliferative fractions of leukemic blasts were also TdT+ and sensitive to lysis with MAb and C'. On the basis of these observations MABs were selected for purging in 36 patients undergoing ABMT in first remission (10 patients considered to be at a high risk of relapse), second and third remissions (23 and 2 patients), and without entering into remission (1 patient). The efficacy of eliminating the MAb-reactive cells from the bone marrow inoculum was also documented in five patients. By the use of sensitive immunologic assay (TdT/cytoplasmic CD3 double staining) in patients with T-ALL, no residual leukemia (less than 10(-4] could be detected at the time of transplantation. Following an observation period of 5-34 months, 24 of the 36 patients are alive and well with no procedure-related mortality.

Antibodies, Monoclonal↗
PubMed1988

Chronic B-lymphocytic leukemia--expression of B cell activation markers in relation to activity of the disease.

Two-color FACS analysis was used to study phenotypic subset and activation markers on circulating B (tumor) cells of 21 patients with chronic B-lymphocytic leukemia (B-CLL). Patients with clinically active (progressive) disease differed from patients with stable disease: B cells from the former patient category showed a significantly increased expression of the activation antigen 1D11 and FN99(CD9), and a decreased expression of the FN1 B subset marker. No clinical associations were observed using the CD23, CD25, 4F2, Ba, Bac-1 or FN50 markers. Functional studies showed that the B cells from both clinical categories of patients responded equally well with DNA synthesis when optimally triggered and supplied with T cell factors. However, B-CLL cells from patients with progressive disease secreted significantly higher levels of IgM in response to phorbol ester. The present experiments thus show that differences exist in the activation of B-CLL cells in vivo and that these patterns are correlated with disease activity. Further, the maximal in vitro proliferative capacity of individual tumor cells is similar, whereas differences in accessory T cell functions may exist between patients.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1987

Prognostic value of serum lactic dehydrogenase (S-LDH) in multiple myeloma.

Serum lactic dehydrogenase (S-LDH) was analysed at diagnosis in ninety-three patients with multiple myeloma. The patients were then followed up after a mean observation period of 39 months (SD 29). Serum lactic dehydrogenase was elevated in twenty-seven out of ninety-three patients and found to correlate with the serum concentrations of beta 2-microglobuline, creatinine, and thymidine kinase. In discriminant analysis of pretreatment S-LDH levels in relation to survival, the best discrimination level was 7.0 mukat 1(-1). Patients with values below 7 microkat 1(-1) ahd a median survival time of 45 months compared to 14 months for those with levels above 7 mukat 1(-1) (P less than 0.001). Serum lactic dehydrogenase at diagnosis, thus, has prognostic information in multiple myeloma.

Humans↗