Transaminase, hepatitis B, and prognosis in acute nonlymphoblastic leukemia.
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Biomedical subjects
Publications and source records attributed to C Haanen.
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Among 164 patients with acute lymphoblastic leukemia (ALL) (age greater than 11 years) induced into complete remission at four hospitals in Italy and The Netherlands between 1971-1977, 49 survived for more than three years in continuous complete remission. Features at diagnosis of the 49 long-term survivors were compared with those of the parent group. The long-term survivors presented with significantly lower leukocyte counts and were slightly younger. Late relapses occurred in nine patients after 37-91 months from remission. Of the 45 patients who had all treatment stopped after 24-60 months of continuous remission, seven have relapsed. Relapses, mainly in the marrow, occurred 4-32 months after cessation of therapy, the risk of relapse being greatest in the first year and dropping to zero by the fourth year. ALL appears curable in approximately one fifth of adolescents and adults entering complete remission with adequate chemotherapy.
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The measurement of color development with time in cells following the start of a staining reaction is of interest in a number of biological systems. These include the subsets of peripheral white blood cells after acridine orange staining, the uptake by cells and nuclei of fluorescent agents, especially antitumor drugs, and measurement of intracellular enzyme kinetics using fluorogenic or absorbing substrates. The present work describes a simple computer program for analyzing flow cytometric (FCM) data versus time, including both the population kinetics of color development and the variability of staining speed within one population of cells. A single-channel absorption measurement in flow (Technicon Hemalog D) was used to record peroxidase kinetics in peripheral blood cells. Every 5 s, a 64-channel absorption histogram was recorded, up to a maximum of 64 histograms. The data were then analyzed by a computer program which searched for the peak channel of each histogram. A least-squares fit was computed for these maxima. The asymmetries of the 64 absorption histograms were compared to see if there was more than one population present with different time constants. Although developed for enzyme kinetic measurements, this program may have wider usefulness in any measurements of time-dependent phenomena by FCM.
Monocyte antibody-dependent cytotoxicity was studied in 19 patients with Hodgkin's disease and 14 normal controls. This function was investigated after isolation of the monocytes by means of a modified elutriation technique. Direct sizing and counting of the cells present in the effluent enabled individual adjustment during each separation procedure. The absolute monocyte count in the peripheral blood of patients with Hodgkin's disease was higher (P less than 0.002) than in normal controls. Nearly 90% pure monocyte suspensions, representing 82% of all elutriated monocytes, were obtained. The elutriation characteristics of the monocytes in both groups were essentially the same, irrespective of marked interindividual differences. Kill of antibody-coated chicken red blood cells was measured by DNA flow cytometry. In comparison to normal controls, a significantly increased (P less than 0.0004), stage-independent, monocyte antibody-dependent cytotoxicity was found in patients with Hodgkin's disease. The percentage of kill in symptomatic patients tended to be higher than in the asymptomatic group; no correlation was found with the absolute number of circulating monocytes.
To evaluate metabolic functionality of monocytes and lymphocytes in Hodgkin's disease (HD) we studied 3 enzymes of the intermediary metabolism, G-6-PDH, PHI, ICDH, and the acid hydrolases, NAG and ACP. These enzymes were measured in purified cell fractions of 9 patients with advanced disease and 11 normal controls. The cells were isolated with cell scatter-monitored counterflow centrifugation. Enzymes were measured in the cell lysates by means of fluorimetric microassays. In the monocytes of HD patients a significantly increased G-6-PDH activity was found (P less than 0.01), indicating an enhanced activity of the hexose monophosphate shunt. The other enzymes showed no clear differences compared to normal controls. The lymphocytes of HD patients showed a significantly augmented activity of both G-6-PDH (P less than 0.001) and PHI (P less than 0.01), pointing to an increased HMPS and glycolytic activity. These findings are in support of an enhanced metabolic activity of both monocytes and lymphocytes in HD.
E-rosetting of leukaemic blast cells is one of the markers of T-cell acute lymphoblastic leukaemia (ALL). In children, E+ ALL has a bad prognosis. In adults, data are scarce. This report provides information on 25 E+ ALL adult patients who have a minimum follow-up time of 36 months. Twenty-two of 25 patients (88%) achieved complete remission (CR) (median duration 16 months), and six of them were alive, relapse-free, and off therapy after 36-81 months, with a 26% projected 6-year relapse-free survival. In 97 patients with E-SmIg- ALL, who were treated at the same Institutions, over the same period of time, and by the same modalities, the outcome of therapy was almost identical: CR 80%, median duration of first CR 15 months, projected 6-year relapse-free survival 15%. The white blood cell (WBC) count at presentation influenced significantly and to the same degree first CR length in both E+ and E- cases. In this adult series, WBC count was not as high as in children. Moreover, a high Hb concentration, a very high WBC count, lymphadenomegaly, and mediastinal involvement, were found more frequently in adolescents and young adults than in adults. Based on these data, it is suggested that in adults E-rosetting as such is not a marker of a poorer prognosis, that some of the typical features of children E+ ALL weaken with age, and that in adults the disease can have a less aggressive character.
This report presents the case history of a 27-year-old woman who developed Thrombotic Thrombocytopenic Purpura (TTP) in the 12th week of her first pregnancy. TTP was successfully controlled with plasma infusions. When plasma infusions were tapered off, TTP relapsed and was followed by eclampsia and fetal death. Plasma infusions were reinstituted until 3 d after delivery. She later suffered relapses manifested by falls in platelet count and haptoglobin level coinciding with the use of an oral contraceptive. After stopping the pill, fluctuations in platelet count and haptoglobin level were observed synchronous with the menstrual cycle (cyclic TTP). The case history described provides evidence for hormonal influences in the genesis of TTP.
Flow-cytometric analysis of bone marrow aspirates and blood samples was performed in 106 adult patients with acute leukemia in order to assess the size and the prognostic significance of the percentage of S-phase cells in the bone marrow (%Sbm). A correction procedure was applied for the fraction of contaminating peripheral nucleated cells in bone marrow aspirates (%Fpb). In 82 out of 106 patients studied, the %Sbm could be reliably determined, and was compared to the %Sbm in 25 healthy controls. The %Sbm in these healthy controls ranged from 8.4 to 14.6%. The median %Sbm in 31 patients with acute nonlymphocytic leukemia (ANLL) at diagnosis (11.3%) and in 14 patients with ANLL at relapse (11.8%) did not differ significantly from the median %Sbm in normal bone marrow (11.7%). On the other hand, in 12 out of 23 patients with acute lymphocytic leukemia (ALL) at diagnosis and in 6 out of 11 patients with ALL at relapse the %Sbm was much higher and ranged from 17.8 to 44.0%. The prognosis of patients with ALL with a high %Sbm (greater than 15%) was significantly worse. Blast cells with an abnormal DNA content (aneuploid cells) were noticed in 7.7% of the patients with acute leukemia at diagnosis. This incidence, however, was significantly higher in ALL patients at relapse (i.e. 42.1%).
Flow cytometric analysis of bone marrow aspirates and blood samples in 42 patients with chronic myelogenous leukemia (CML) at various disease stages was performed to determine the size of the S-phase compartment of bone marrow and blood. 25 healthy controls were studied for comparative information with both DNA-flow cytometry (DNA-FCM) and 3H-thymidine autoradiography. A correction procedure was applied for peripheral nucleated cell admixture in bone marrow aspirates. The fraction of peripheral nucleated cells in bone marrow aspirates (Fpb) in individual patients was considerable, especially in those with a very high white blood cell count (greater than 100 x 10(9)/l). The size of the S-phase compartments of bone marrow (% Sbm) in patients with CML at diagnosis and in patients at apparent hematological remission was of the same order of magnitude as in normal bone marrow. However, in 3 out of 4 patients at malignant metamorphosis in which the % Sbm could be reliably determined, this percentage was significantly higher than normal (p = 0.013). In 4 out of 11 patients at malignant metamorphosis aneuploidy was noticed. From these findings it is concluded that bone marrow cell proliferation in CML patients at diagnosis and during apparent remission is not essentially different from normal. However, at malignant metamorphosis changes occur in ploidy level and proliferative activity, which can be detected by DNA-FCM already in an early phase.
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Monocytes purified with cell scatter monitored counterflow centrifugation were cultured in plastic (adherent) and in teflon culture bags (suspension). Sequential changes were monitored during 15 days by measuring intracellular activity of three enzymes of intermediary metabolism: glucose-6-phosphate dehydrogenase (G-6-PDH), phosphohexose isomerase (PHI) and isocitrate dehydrogenase (ICDH), and the two acid hydrolases: acid phosphatase (ACP) and N-acetyl-beta-glucosaminidase (NAG). In teflon grown macrophages a significantly lower G-6-PDH activity was seen after 15 days in comparison to plastic adherent macrophages (P less than 0.0002). For the other enzymes similar values for both culture modalities were found. The significantly, cycloheximide insensitive, higher values for G-6-PDH, PHI and ICDH in 2 h plastic adherent monocytes in comparison with plastic non-adherent monocytes, suggest a relationship between adherent capacity and the level of intermediary metabolism. The overall yield of plastic adherent macrophages after 15 days was 35% in contrast with 89% for the in suspension cultured macrophages. This corroborates the existence of adherent and non-adherent monocytes, both capable of differentiation in vitro. In 14 patients with advanced Hodgkin's disease (HD) and 14 normal controls, monocyte differentiation was studied applying both culture modalities. The enzyme levels, reflecting growth and intermediary metabolism, were similar for both groups. The adherent capacity and yield, both in teflon and in plastic, after 15 days was comparable for both groups. It was concluded that in vitro monocyte differentiation in the presence of autologous serum was qualitatively and quantitatively normal in advanced HD; this is in favour of an intrinsically normal function of monocytes in HD.
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From 20 patients with solid tumors or acute nonlymphocytic leukemia in remission, hemopoietic progenitor cells were taken and stored in liquid nitrogen, for use in autologous bone marrow transplantation. Bone marrow aspiration resulted in a volume of 920(+/- 170) ml containing 16.8(+/-6.0) x 10(9) nucleated bone marrow cells and 7.2(+/-4.4) x 10(6) myeloid progenitor cells (CFUc). With use of the Haemonetics blood cell separator a progenitor cell-enriched fraction is obtained. This fraction is depleted of 90(+/-6)% of the erythrocytes and 59(+/-15)% of the neutrophils contained in the original. The original aspirate volume is reduced to one-fifth (21 +/- 3%) while containing 88(+/-38)% of the original CFUc's and 52(+/-11)% of the nucleated bone marrow cells. This technique of bone marrow enrichment has the advantage of a minimum of open-air contact, being independent of extensive laboratory facilities and manpower. The enriched fraction is frozen in autologous plasma and a final concentration of 10% (v/v) DMSO, using a program-controlled freezer (L'Air Liquide). Materials are stored at liquid nitrogen temperature in bags (Gambro) and test vials. Total CFUc recovery in test vials after thawing was 81(+/-32)%.
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