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Biomedical subjects

R Hast

Publications and source records attributed to R Hast.

At least 55 records · Page 3Linked to original sources
PubMed1993

Comparison of acute myeloid leukemia occurring de novo or preceded by a myelodysplastic stage: differences in cellular DNA content.

The DNA content of bone marrow cells in patients with acute leukemia preceded by a myelodysplastic stage (MDS-AML) was compared to that in patients with de novo AML. We studied granulocytes, lymphocytes, monocytes, and blasts/promyelocytes from Feulgen-stained bone marrow smears of 11 patients with de novo AML, ten patients with MDS-AML, and 13 apparently healthy controls. The mean amount of DNA per cell (DNA index; DI) in each cell population was determined using a digital video-based image-analyzing system (CAS-100). Analysis of variance (F test) showed a significant difference in the DNA content between de novo AML on one hand and MDS-AML and controls on the other as regards to blasts/promyelocytes (P < 0.01), lymphocytes (P < 0.05), and monocytes (P < 0.01), respectively. In three of 11 (27%) patients with de novo AML, a lower than normal limit DI was found both in immature and mature bone marrow cells. Patients with MDS-AML had those of DI values similar to normal controls. In consequence, a significantly reduced mean DI was found in patients with de novo AML in blasts/promyelocytes (P < 0.01), and monocytes (P < 0.05) compared to both normal controls and MDS-AML. Together with data published separately, suggesting differences in granulocyte morphology, clonality, and HLA-DR expression, these data suggest biological differences between the two diseases.

Adolescent↗
PubMed1993

Variation in DNA content of immature normal bone marrow cells.

A variability in DNA content detected was found with image cytometry, in immature bone marrow cells from 13 healthy donors (median age 31 yr). The mean coefficient of variation (C.V.) of the DNA content was found to be significantly (P = 0.0002) higher in immature blasts and promyelocytes than in mature granulocytes, lymphocytes, and monocytes. The finding was not due to high DNA contents secondary to DNA-synthesis in immature cells, since the percentage of such cells with a reduced DNA content was also significantly (P = 0.0424-0.0002) increased. The error of the method expressed as the variance of multiple measurements has been found to be 0.0002-0.0004. A staining error has been found for some hydrolysis times, but not for times between 60 and 120 minutes. A measuring error was found for an average of 1.38 to 3.38% of the cells. If many normal cells with DNA-aneuploidy are sterile, this would explain the present findings as well as previous ones about intra-marrow cell death, and also the fact that the variability in DNA content could not be detected with cytogenetic or flow cytometric methods.

Adult↗
PubMed1993

Intensive treatment in order to minimize the Ph-positive clone in chronic myelogenic leukemia.

Several studies indicate that interferon (IFN) treatment, intensive chemotherapy and autologous bone marrow transplantation (ABMT) effectively reduce the Ph-positive clone in Chronic Myelogenic Leukemia (CML). In the present study on patients < or = 55 years, we have combined these three treatment modalities. The aim of the study was to eliminate or minimize the Ph-positive clone to see whether a status of minimal residual or Ph-negative disease could be maintained for a longer period of time. After diagnosis, patients received interferon (IFN-a-2b) and hydroxyurea (HU) to keep the white blood cell (WBC) and platelet count below 2-4 and 100-150 x 10(9)/l, respectively. After six months of treatment, Ph-analysis was performed. Patients with Ph-positive cells in bone marrow then received 1-3 courses of intensive chemotherapy. In patients Ph-negative after two courses, bone marrow was harvested and used for ABMT. After a third course, patients with up to 50% Ph-positive metaphases were accepted for ABMT. As of January 1, 1993, 97 patients were registered in the study. Six months of IFN+HU reduced the percentage of Ph-positive metaphases in 57% of the patients (7% became Ph-negative). The corresponding figures after two intensive cytotherapies were 70% (40% Ph-negative). Eighteen patients were autotransplanted. Seven have relapsed with Ph-positivity 3-22 months after ABMT, while nine are Ph-negative at 1-32+ months after ABMT (two not yet analyzed). Seventeen patients are alive and well, while one died one month after ABMT due to interstitial pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Methodological aspects of DNA image cytometry in normal bone marrow smears.

The possibility of using DNA image cytometry in hematological material was evaluated in 27 Feulgen stained normal bone marrow smears. The 95% normal limits of DNA index (DI) determined separately for each cell population in bone marrow were 0.89-1.15, 0.93-1.09 and 0.92-1.12 for blasts, granulocytes and lymphocytes, respectively. The mean DI for blasts, granulocytes and lymphocytes was 1.02, 1.01 and 1.02, respectively. In the blasts population the mean percentage of cells in S+G2/M phase was 38.1% (S.D. 12.9%, range 14.3-65.6%), whereas the corresponding values for granulocytes and lymphocytes were below 1%. Calculation of DI and G0/G1 C.V. obtained in bone marrow smears subjected to Feulgen hydrolysis (5 N HCl, 22 degrees C) for different periods of time revealed the presence of a plateau of results between 60 and 120 min for all of the cell types. The intraobserver and interobserver reproducibility was confirmed by duplicate measurements of each subpopulation (P > 0.05). A comparison of DI and G0/G1 C.V. using smears from the same donors stained with the Feulgen method either straight away or after destaining from May-Grunwald-Giemsa confirmed that destained smears can be used, provided applying appropriately prepared reference cells. We conclude that image cytometry can be used reliably to analyze DNA content in hematological material.

Adolescent↗
PubMed1993

Prediction of response to treatment with human recombinant erythropoietin in myelodysplastic syndromes.

The effect of human recombinant erythropoietin (rhEPO) was investigated in 29 anemic patients with myelodysplastic syndromes (MDS). A rhEPO dosage of 150 U/kg was administered subcutaneously three times weekly for a minimum of 6 weeks. Seven out of 27 evaluable patients (26%) had an effective clinical response to therapy by increasing hemoglobin concentrations by more than 15 g/l (reaching at least 105 g/l) or by eliminating transfusion requirements. Six out of the seven patients responded within four weeks. Three of the responders successfully continued rhEPO treatment 15 months or more. To determine whether it may be possible to predict response to rhEPO, various clinical parameters were examined. Responders were found to be significantly different from non-responders in five aspects: They had less elevated baseline serum EPO levels (92 +/- 33 versus 515 +/- 108 U/l, mean +/- SEM; p = 0.023) and were more often transfusion-independent (71% versus 20% of non-responders; p = 0.022). Furthermore, responders were more often females (71% versus 40% in the non-responding group; p = 0.025), of subtype RA rather than RAEB (four patients and one patient, respectively, compared to seven and nine patients in the non-responding group; p = 0.025), and they predominantly displayed normal karyotypes or a 5q- aberration (86% versus 47%; p = 0.005). We conclude, that rhEPO treatment can reduce anemia in MDS and that certain pre-treatment clinical parameters may be used to predict response.

Aged↗
PubMed1992

Therapeutic aspects of myelodysplastic syndromes in chronic phase.

Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients should generally be treated conservatively. Transfusions of packed red cells (given in a strict regimen to minimize the risk for secondary hemochromatosis) may be sufficient to maintain a good quality of life. Indications for cytotoxic treatment include signs of progression of the disease. In patients with symptomatic cytopenias low-dose cytarabine (ara-C) should be tried. It is essential then to monitor each patient individually and to avoid fixed treatment schedules. Standard (high-dose) chemotherapy in MDS, is associated with a high mortality and a low response rate, and should be considered only in younger patients with advanced MDS. Allogeneic bone marrow transplantation (BMT) may be offered to younger MDS patients, when a suitable donor is available. Treatment with differentiation inducers has not met with expectations and should not be used outside clinical trials at the present. The use of recombinant hemopoietic growth factors (GF) seems promising. GF, like GM-CSF, G-CSF, IL-3, and erythropoietin, can be used either alone or in combinations, to support failing peripheral blood values, and decrease the risk for lethal complications. GF can also be given together with chemotherapy, in an effort to make the leukemic clonogenic cells more susceptible to cytotoxic drugs. Other treatments for MDS include: IFN-alpha and etoposide, with responses primarily in chronic myelomonocytic leukemia; hem arginate, whose role is still not clear; and corticosteroids, but only in carefully selected cases.

Antineoplastic Agents↗
PubMed1992

Dysplastic peripheral blood polymorphs link acute myeloblastic leukaemia in elderly to the myelodysplastic syndromes.

We studied dysplastic features in peripheral blood polymorphs from 80 patients with acute leukaemia. Thirty-seven patients with de novo acute myeloblastic leukaemia (AML) were compared to 26 patients with AML that had developed after a myelodysplastic phase (MDS-AML), and 17 cases of acute lymphoblastic leukaemia (ALL). Cytoplasmic hypogranulation in neutrophils, measured as a score value (G-score; normal range: 255-300), and the percentage of pelgeroid polymorphs (ppp; normal range: 0.5%) were studied retrospectively by reviewing the diagnostic peripheral blood smears. The mean G-score was decreased in MDS-AML (178 +/- 67.9), and in de novo AML (212 +/- 65.1), but not in ALL (275 +/- 24.3). When de novo AML patients were divided by age, the elderly (greater than 60 yr) had significantly (p = 0.0001) lower mean G-score than the younger (less than 45 yr) ones; 156 +/- 64.8 v 243 +/- 41.4. This age-related difference became accentuated when only patients with extreme hypogranulation (G-score less than 150) were studied. Elderly de novo AML patients also had significantly (p = 0.0057) higher mean ppp. By studying the degree of polymorph dysplasia in the peripheral blood, it seems possible to identify a subset of dysplastic elderly AML patients, who might have passed a (preleukaemic) MDS phase unnoticed.

Adolescent↗
PubMed1991

Treatment of multiple myeloma with interferon alpha: the Scandinavian experience.

IFN alpha is a biologic therapeutic agent with documented antitumoral effect in multiple myeloma. 15% of previously untreated myeloma patients achieve a clinical response to IFN alpha alone with a possible dose-response relationship. A particularly good effect is noted in IgA myelomas treated with natural IFN alpha. A randomized study was started in April 1986 comparing melphalan/prednisone (MP) therapy with MP plus natural IFN alpha (MP/IFN) in untreated patients with multiple myeloma stages II and III. 220 patients had entered the study by autumn 1989. An interim report is given here. The response frequency was 48% in the MP group and 66% in the MP/IFN group (P less than 0.02). Stage II patients responded better to MP/IFN (76%) than to MP alone (48%) (P less than 0.01). No significant difference was noted for stage III patients. 91% of all IgA myelomas responded to MP/IFN and 52% to MP (P less than 0.01). The difference in response frequency of IgG and BJ myelomas between the two treatment groups was not statistically significant. The observation period is still too short to draw firm conclusions on survival. However, a statistically significant longer response duration time and survival from response (P less than 0.01) was noted for stage II patients.

Antineoplastic Combined Chemotherapy Protocols↗