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Biomedical subjects

R Hast

Publications and source records attributed to R Hast.

At least 73 records · Page 4Linked to original sources
PubMed1990

Oral versus intravenous melphalan and prednisone treatment in multiple myeloma stage II. A randomized study from the Myeloma Group of Central Sweden.

Eighty-one previously untreated patients with multiple myeloma stage II entered a randomized trial comparing oral melphalan (0.25 mg/kg/day; n = 40) with intravenous melphalan (0.125 mg/kg/day; n = 41) in combination with oral prednisone (2 mg/kg/day). The courses were given for 4 days and repeated every sixth week. The treatment groups were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, the response duration times and the survival times. No significant difference in nonhematological and hematological toxicity was noted. Since intravenous administration of melphalan did not result in a substantial increase in response rate or survival, this study supports the use of oral melphalan/prednisone as first-line therapy for patients with multiple myeloma.

Actuarial Analysis↗
PubMed1989

Cimetidine as an immune response modifier.

Cimetidine, a selective histamine-2 receptor antagonist, has attracted interest because of its potential as an immune response-modifying drug. Most data suggest that cimetidine has a stimulatory action on the immune system, possibly by blocking of receptors on subsets of T-lymphocytes and inhibiting histamine-induced immune suppression. Several studies have shown that cimetidine can affect the relative number of CD8 + ve lymphocytes and increase the NK cell activity as well as the antibody-dependent cellular cytotoxicity. Cimetidine has also been used successfully to restore immune functions in patients with malignant disorders, hypogammaglobulinemia and AIDS-related complexes.

Adjuvants, Immunologic↗
PubMed1989

Diagnostic significance of dysplastic features of peripheral blood polymorphs in myelodysplastic syndromes.

Dysplastic features of peripheral blood granulocytes were studied to investigate the diagnostic value estimating cytoplasmatic hypogranulation and nuclear abnormalities of the pelgeroid type in myelodysplastic syndromes (MDS). Hypogranulation was measure both as the percentage of agranular neutrophils and as a score value, taking into account also cells with slight or moderate hypogranulation. We studied 62 cases of MDS (18 refractory anemia, 11 sideroblastic anemia, 26 refractory anemia with excess of blasts, three chronic myelomonocytic leukemias, four refractory anemia with excess of blasts in transformation). For comparison we studied 13 cases of myeloproliferative disorders, 18 patients with different forms of anemia and 20 normal controls. Reference values were defined as the 95% probability limit of the mean values of normal controls. In MDS 52/62 patients (84%) had increased numbers of pelgeroid cells, 40/62 (65%) had abnormal granulation scores while only 14/62 (23%) had increased percentages of agranular neutrophils. The mean granulation score (+/- S.D.) in MDS (225.0 +/- 57.4), was significantly lower (p less than 0.001) than in myeloproliferative disorders (282.7 +/- 9.0), anemias (288.8 +/- 8.0) and normal controls (281.7 +/- 12.9). Pelgeroid neutrophils were significantly (p less than 0.001) more common in MDS (11.6% +/- 7.8) compared to myeloproliferative disorders (1.1% +/- 1.0), anemias (3.1% +/- 2.0) and normal controls (1.9% +/- 1.5). There was no significant correlation between the degree of hypogranulation and the percentages of pelgeroid cells in individual patients. Hypogranulation tended to be more pronounced in the more immature forms of MDS while pelgeroid cells were equally common in the different subgroups. When the two parameters were combined peripheral blood dysplasia was recognized in 92% of the MDS cases. The results suggest that quantitative estimation of hypogranulation and of nuclear abnormalities in peripheral blood polymorphs are simple and valuable diagnostic tools in MDS.

Aged↗
PubMed1989

Induction treatment with alpha-interferon in multiple myeloma: an interim report from MGCS.

A randomized study comparing melphalan/prednisone (M/P) therapy with MP + natural alpha-IFN in untreated patients with multiple myeloma stages II and III started April 1, 1986. By March 1989, 78 patients were evaluable in the MP group and 80 in the MP/IFN group. 48% of the MP patients achieved a response and 66% in the MP/IFN group (p = 0.04). Stage II patients responded better to MP/IFN (76%) than MP alone (47%) (p = 0.02), while no statistically significant difference was noted for stage III patients. 90% of the IgA myelomas responded to MP/IFN and 52% to MP (p = 0.02). Both for IgG and BJ myelomas the response rates of MP/IFN were higher than of MP, although the differences were not statistically significant. The observation period is still short. There was no difference in total survival between the two treatment groups. However, in patients less than or equal to 65 years a tendency to a longer survival was seen for those receiving the IFN combination (p = 0.12).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Decreased blood natural killer cell activity and immunoglobulin synthesis in vitro in aplastic anemia.

Natural killer (NK) cell numbers and T lymphocyte subpopulations in peripheral blood were evaluated in six patients with aplastic anemia (AA). The immunophenotyping results were correlated to in vitro tests of NK cell cytotoxicity against K562 cells and of immunoglobulin (Ig) production after pokeweed mitogen (PWM) stimulation. A significant decrease was found both in the percentage of Leu 11 positive cells and in NK cell activity as compared to age- and sex-matched healthy controls. The decrease in NK cell activity could not be entirely compensated by an increase in effector/target cell ratios, thus suggesting not only a quantitative but also a functional defect in NK cells of the AA patients. Three of four AA patients tested showed no major increase of Ig production after PWM stimulation. All these three patients also had fewer "functional T helper" cells (Leu3+/Leu8-) and increased numbers of T suppressor/cytotoxic cells (Leu2+) when compared to controls. No significant differences in numbers of B lymphocytes (B1+) could be found. Our findings suggest a possible linkage between quantitative and qualitative abnormalities in lymphocyte subsets in aplastic anemia. However, no evidence was found to support the hypothesis of increased NK cell activation behind the hemopoietic depression in this disease.

Adolescent↗
PubMed1987

Cyclosporine A treatment in four cases of aplastic anemia.

Cyclosporine A (CyA) treatment of 4 patients with severe aplastic anemia, who were ineligible for bone marrow transplantation, was carried out for periods of between 12 weeks to 20 months. A normalization of Hb and bone marrow, together with a marked improvement in WBC and platelet counts, were observed in only one of these four patients. The remission was maintained for 20 months under continuous treatment. A relapse occurred only when the patient himself interrupted treatment. No serious side effects were observed with CyA doses of 4-10 mg/kg/daily and blood concentrations of 200-400 ng/ml. No significant changes in T helper/T suppressor ratios were noted during the course of CyA treatment.

Anemia, Aplastic↗
PubMed1987

Balloon-like platelets in myelodysplastic syndromes--a feature of dysmegakaryopoiesis?

Large bizarre platelets are a frequent finding in the peripheral blood of the myelodysplastic syndrome (MDS). In this study we describe a distinct subpopulation of platelets in MDS which by phase contrast microscopic examination seems to have a balloon-shaped bulge of the cell membrane. Increased numbers of these atypical platelets were found in 24 of 27 MDS patients (89%). Only 3 patients, all with ringsideroblastic anemia, had normal platelet morphology. The number of atypical platelets were negatively correlated (r = 0.44; p = 0.021) to the peripheral platelet counts in MDS. Among 48 patients with acute leukemia, chronic lymphoproliferative or chronic myeloproliferative disorders, 13 (27%) had atypical platelets. Here, but not in the MDS group, atypical platelets seemed to be associated with recent chemotherapy. In a group of patients with benign hematological disorders abnormal platelet morphology was seen only occasionally. The described atypical platelets most likely reflect maturation disturbances of the megakaryopoiesis. An increased value (greater than 1%) in a cytopenic patient would suggest a diagnosis of MDS, unless associated with recent cytotoxic therapy.

Antineoplastic Agents↗
PubMed1986

Effects of retinoids on in vitro differentiation of bone marrow cells in the myelodysplastic syndrome.

The effect of retinoids on cell differentiation in the myelodysplastic syndrome was studied in short-term liquid cultures of bone marrow from 13 patients. After incubation with 13-cis-retinoic acid there was a significant decrease in the percentages of promyelocytes and in Leu-M3-binding cells. Lue-M3 is mainly a monocyte marker, and retinoids thus seem to induce a shift from monocytoid to myeloid differentiation. Patients with refractory anemia with an excess of blasts responded the most, and did also show a significant decrease in OKIa1-binding cells. Etretinate, on the other hand, did not show any differentiation-inducing activity. The results support earlier reports that retinoic acid might be useful in the treatment of the myelodysplastic syndrome. Whether this in vitro technique offers a possibility to predict the clinical outcome remains to be shown.

Aged↗
PubMed1986

Decrease in helper (T4+) lymphocytes following cimetidine treatment for duodenal ulcer.

We studied the possible in vivo influence of cimetidine on peripheral blood lymphocyte (PBL) subpopulations defined with monoclonal antibodies (MoAb) in eight haematologically normal patients with uncomplicated duodenal ulcers before cimetidine treatment, 1 week after the start, and finally 1 week following cessation of therapy. After cimetidine had been given for 3-5 weeks there was a significant decrease, compared with pretreatment numbers, in the proportion of T3+ cells (64.6 +/- 8.1 (mean +/- s.d.) v 51.0 +/- 7.8%) and in T4+ cells (47.3 +/- 4.3 v 30.8 +/- 4.7%). The number of T8+ cells was not affected (20.3 +/- 4.3 v 20.1 +/- 6.7%). These changes resulted in a significant reduction in the T4/T8 ratio (2.46 +/- 0.8 v 1.67 +/- 0.6). The total numbers of lymphocytes and monocytes as well as the percentage of B1+ lymphocytes did not change significantly. The observed decrease in T4/T8 ratio after cimetidine treatment is explained by a reduction in the number of T4+ cells and the appearance of a new subpopulation of T3-, T4-, T8-, B1-lymphocytes. The underlying mechanism, however, is not clear. Cimetidine does not seem to have a direct receptor-modulating effect, since in vitro exposure of normal lymphocytes to the drug did not change the proportions of the T cell subsets.

Adult↗
PubMed1986

Staging of leukemic progenitor cells in acute myeloid leukemia by phenotyping with myeloid monoclonal antibodies.

We studied the immune phenotype of leukemic progenitor cells (AML-CFU-L) in 16 cases of acute myeloid leukemia (AML) using 12 myeloid monoclonal antibodies (McAbs) in a complement-mediated cytotoxicity assay. On the basis of their reactivities with normal day-14 (D14) and day-7 (D7) myeloid progenitor cells (CFU-GM), these McAbs could be classified into three groups: six McAbs reacted strongly with "early" antigens on D14-CFU-GM, two McAbs reacted only with "late" antigens on D7-CFU-GM, while four McAbs formed an "intermediate" group that reacted both with the "late" antigens on D7-CFU-GM and to some extent with the "early" antigens of D14-CFU-GM. The McAbs all reacted with antigens on AML-CFU-L:McAbs that reacted with "early" antigens reacted consistently strongly with AML-CFU-L, in contrast to McAbs in the two other groups, which displayed greater heterogeneity. On the basis of antigenic phenotype, the predominating CFU-L in AML could thus be placed in one of three "stages." This phenotypic "staging" of AML correlated with the French-American-British (FAB) morphological classification of AML. The AML-CFU-L of patients with FAB morphological types M2, M4, and M5 expressed more differentiated antigenic phenotypes than those of the three patients with M7. The latter reacted poorly with the "intermediate" and "late" McAbs. Our data and those of others suggest that classification based on AML-CFU-L antigenic profile may complement the FAB classification of AML.

Adolescent↗
PubMed1986

Endogenous erythroid colony formation in myeloproliferative diseases does not depend on T cells.

We investigated the influence of T-cell depletion on BFU-E and CFU-GM colony growth in vitro from normal individuals and patients with chronic granulocytic leukemia (CGL), idiopathic myelofibrosis (MF), and polycythemia vera (PV). Preincubation of mononuclear cells with the complement-fixing monoclonal antibody OKT11A, which is cytotoxic to T-lymphocytes, significantly reduced the number of erythropoietin (epo)-dependent BFU-E colonies cultured from normal bone marrow and normal peripheral blood, as well as from the blood of patients with CGL, PV, and MF. In contrast, the numbers of epo-independent ("endogenous") BFU-E colonies cultured from the blood of PV and MF patients were the same before and after T-cell depletion. The blood and marrow of CGL patients and normal individuals produced no epo-independent BFU-E proliferation. The growth of day-7 and day-14 CFU-GM was not significantly influenced by T-cell depletion in the majority of experiments. We conclude that T cells promote the growth of epo-dependent BFU-E colonies in vitro, but they do not influence the growth of "endogenous" BFU-E colonies from patients with myeloproliferative disorders.

Adult↗
PubMed1985

Cytotoxicity of monoclonal antibodies against individually immunophenotyped human leukemic cells.

Peripheral blood and bone marrow mononuclear cells from 12 patients with acute myeloid leukemia (AML), 2 patients with acute lymphatic leukemia, and 1 patient with chronic myeloid leukemia in blastic crisis were taken at diagnosis or in relapse. Cells were immunophenotyped with a panel of monoclonal antibodies (Moab) (OKIa, Leu M1, Leu M2, Leu M3, Leu M4, B1, Okt 11, J5) and the same antibodies were used in an in vitro cytotoxicity test. Of the 14 patients, 10 had antibody-binding cells, and the percentage of lysed cells was almost equal to that of blasts. The other 4 patients had few binding cells and little lysis. Acute leukemia with and without preceding myelodysplastic features did not differ in immunophenotype. Mean spontaneous release of 51Cr was 12.7% and complement alone caused an additional average release of 11.8%. Four single antibodies together with complement showed a mean 51Cr release of 0.7-32.4% above that found with complement alone. Combinations of Moabs resulted in 51Cr release at least 10% above the single most efficient Moab in 8 out of 12 patients. Not all blast cells showed antibody binding, nor were all antibody-binding cells susceptible to cytotoxicity. Normal bone marrow growth in vitro seemed to be stimulated by factors in complement and in the Moab. When this stimulation was compensated for by adding fetal calf serum, cytotoxicity tests prior to CFUc assays resulted in a mean decrease of 46% of colonies and 25% of clusters in normal bone marrow. CFUc are thus sensitive to the cytotoxicity, although CFU may also be resistant.

Antibodies, Monoclonal↗