Osmotic behavior of normal and leukemic lymphocytes.
(41/1986)
The response of normal human peripheral blood lymphocytes to a hypotonic environment may be divided into two phases: the cells first exhibit rapid osmotic swelling, followed by a slower shrinking phase, during which they regain their initial physiologic volume. This osmotic behavior is characteristic of most mammalian and avian nucleated cells so far examined. The normal human blood lymphocyte, however, shows the most rapid recovery phase (5 min). Lymphocytes from chronic lymphatic leukemia patients, in comparison, show a strikingly slower rate of return to their initial isotonic volumes. The mechanism underlying osmotic cell volume regulation and its significance are discussed. (+info)
Acute lymphoblastic leukaemia: cyclical chemotherapy with three combinations of four drugs (COAP-POMP-CART regimen).
(42/1986)
Forty-two adults and children with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a programme of chemotherapy in which three combinations, each of four drugs were administered in a predetermined cyclical rotation together with cranial irradiation and intrathecal injections of methotrexate. Forty-one patients (98%) entered remission and no patient developed neuroleukaemia. Relapse of ALL occurred in 10 patients, and three patients died during remission, while eight patients stopped treatment after two and a half years and have remained in remission for two to 26 months. Comparison of remission and survival experience in this mixed group of children and adults with the experience of children treated at Memphis and in the Medical Research Council's UKALL-I trial showed no significant differences. On the other hand, analysis by prognostic factors showed that neither age nor blast cell count at presentation had any adverse effect in patients treated in this study. No relapses occurred in nine patients with blast cell counts greater than 20 x 109/1 at presentation. This regimen is effective treatment for ALL and may be of special value in patients with poor prognoses. The regiment has not as yet proved superior for the treatment of children with ALL who do not have adverse prognostic features. (+info)
Serial observations on terminal deoxynucleotidyl transferase activity and lymphoblast surface markers in acute lymphoblastic leukemia.
(43/1986)
Terminal deoxynucleotidyl transferase activity and cell surface markers were measured in peripheral lymphoid cells from 27 children with acute lymphoblastic leukemia in various phases of their disease. Lymphoblasts from untreated patients had smooth surface ultrastructure but heterogeneous surface receptors. Greater than 60% of lymphoblasts from 4 to 7 untreated patients formed rosettes with sheep red blood cells. Transferase activity was variable, ranging from 8 to 210 units/10(8) blasts, but it was consistently elevated at diagnosis and in relapse. Transferase levels did not correlate with the presence of lymphoblast surface receptors. During induction therapy transferase activity decreased rapidly, but it remained elevated in peripheral lymphoid cells even when blasts were not detectable in peripheral blood smears. Patients in remission had normal surface receptors and undetectable or minimally elevated levels of transferase. Terminal transferase activity may be a sensitive biochemical marker for a primitive cell population and may be important in the evaluation of therapeutic effectiveness in acute lymphoblastic leukemia. (+info)
Cytotoxic effects on splenic ultrafiltrates upon leukaemic lymphocytes.
(44/1986)
Ultrafiltrates from spleen inhibited both DNA synthesis and the proliferation of normal lymphocytes stimulated inculture from both mouse and man without apparent cytotoxicity. However, the same doses of this spleen ultrafiltrate will kill up to two-thirds of the leukaemic lymphoblasts from both mouse and man after 24 h incubation. This unique lymphocytotoxic effect could also be demonstrated on fresh primary cultures of leukaemic lymphocytes and was highly effective on slowly growing established cell lines under crowd culture conditions. Furthermore. ultrafiltrated thymus extract did not affect the DNA synthesis rates of the viability of NC-37 lymphoblasts, which have B cell characteristic. Thymus extract was cytotoxic to Molt cells, which have T cell characteristics. (+info)
Drug-induced stimulation of transport of hydrolyzed nitrogen mustard and choline by normal and leukemic human cells in vitro.
(45/1986)
The effect of morphine and cocaine on the transport of hydrolyzed nitrogen mustard (NH2-OH) and choline by peripheral blood cells of normal subjects and patients with chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloblastic leukemia was determined. Transport of HN2-OH by lymphocytes from normal individuals and patients with chronic lymphocytic leukemia was stimulated by morphine and cocaine and, in each case, the effect was statistically significant (P less than 0.05 or greater). However, choline transport by normal lymphocytes was not altered by cocaine and was only slightly stimulated by morphine; choline transport by lymphocytes from patients with chronic lymphocytic leukemia was not stimulated by either morphine or cocaine. HN2-OH and choline transport by cells from patients with either acute lymphoblastic or myeloblastic leukemia was stimulated to a comparable degree by both drugs. Stimulation of HN2-OH transport by morphine and cocaine was greater in normal lymphocytes than in acute leukemic cells and the differences were highly significant (p less than 0.001). Conversely, stimulation of choline transport was more marked in acute leukemic cells than in normal lymphocytes, and these differences were also highly significant (p less than 0.001). It was previously shown that transport of nitrogen mustard by normal and leukemic human cells was biphasic in nature, consisting of a choline-independent component at "high" drug concentrations and a choline-dependent system at "low" substrate concentrations. The preferential stimulation of the low-dose, choline-dependent system by morphine and cocaine in acute leukemic cells relative to that observed in normal lymphocytes suggests a possible mechanism of increasing the therapeutic index of nitrogen mustard. (+info)
Concanavalin A-induced agglutination of human leukemic and lymphoma cells.
(46/1986)
With a newly developed turbidometric method, concanavalin A was shown to agglutinate normal lymphocytes, lymphoma cells, and leukemic cells from chronic lymphocytic leukemia and from acute myelocytic and lymphocytic leukemia. However, there was a marked difference in the kinetics of this agglutination process. Leukemic blast cells and cells from a patient with convoluted lymphoma agglutinated poorly in this system. Conversely, the degree of agglutination for chronic lymphocytic leukemia cells was greater than that for the blast cells and also slightly greater than that for normal lymphocytes. Cultured cells from a Burkitt's lymphoma (Raji) and from a patient with poorly differentiated lymphoma agglutinated very rapidly with concanavalin A. Prior incubation of all cell types with neuraminidase markedly enhanced the agglutination process similar to that of trypsinization. Thus, these studies illustrate the usefulness of this method in quantitating the kinetics of agglutination of various human neoplastic cell types by concanavalin A. (+info)
Treatment of acute lymphocytic leukemia by high-dose intravenous methotrexate.
(47/1986)
A pharmacokinetic study of methotrexate levels in blood and cerebrospinal fluid was performed in 42 patients who received one or more courses of high-dose methotrexate at 500 mg/sq m infused i.v. over a 24-hr period. Methotrexate level in the lumbar cerebrospinal fluid reached 1.2 x 10(-7) M at 0.5 hr and remained constant at that level for the 1st 24 hr. Similar methotrexate levels were noted in the ventricular fluid obtained through an Ommaya device on three patients with brain tumors treated with high doses of methotrexate. Preliminary clinical results using high-dose methotrexate combined with simultaneous intrathecal methotrexate in 23 children with newly diagnosed acute lymphocytic leukemia indicate that this treatment program is safe to administer and to date appears effective in the prevention of central nervous system leukemia. (+info)
Adenosine deaminase activity in peripheral blood cells of patients with haematological malignancies.
(48/1986)
Adenosine deaminase (EC 3.5.4.4, ADA) has been assayed in lymphocytes, granulocytes and erythrocytes from 45 patients with haematological malignancies. Activities were uniformly low in lymphocytes from patients with chronic lymphocytic leukaemia. Variable, but abnormal activities were frequently found in multiple myeloma, untreated lymphoma and leukaemic reticuloendotheliosis. High values were observed in lymphocytes from patients with lymphoma during intensive combination chemotherapy. ADA levels in lymphocytes were not correlated with levels in granulocytes or erythrocytes. ADA was elevated in blasts of patients with acute lymphocytic and myelogenous leukaemias but the ranges of activities per cell were so similar that ADA assay is unlikely to be of major help in distinguishing the two diseases. (+info)