Separation of leukemic and nonleukemic subpopulations of spleen cells from mice with myeloid leukemia.

Centrifugal elutriation has been adapted for use in obtaining highly enriched populations of leukemic myeloblasts and normal appearing lymphocytes from RFM/UN mice with myeloid leukemia. The myeloblasts were functionally intact as evidenced by their high cloning efficiency in vitro and malignant potential in vivo. The lymphocyte-enriched subpopulation had a low thymidine labeling index, and cloning efficiency in vitro, and was only marginally malignant in vivo indicating minimal contamination by leukemic myeloblasts.

A simplified method for determination of daunorubicin, adriamycin, and their chief fluorescent metabolites in human plasma by high-pressure liquid chromatography.

A simple method was developed for the routine monitoring of daunorubicin (DR) or adriamycin (ADR) and of their chief fluorescent metabolites in plasma of cancer patients. The plasma samples were treated with ethanol: hydrochloric acid mixture, following which the drug and its metabolites, released to the 40,000 g supernatant, were analyzed by HPLC. A mu-bondapak-phenyl column was used and an isocratic mobile phase consisting of acetonitrile in 0.

Recognition of drug resistance during remission induction therapy for acute non-lymphocytic leukemia: utility of day 6 bone marrow biopsy.

While the majority of patients under 70 years of age with acute non-lymphocytic leukemia enter remission when treated with a combination of cytosine arabinoside and an anthracycline antibiotic, 20-45% of patients do not. The reasons for treatment failure in these patients vary from drug resistant disease to death from infection or bleeding shortly after remission induction therapy is initiated. Clearly, more intensive remission induction therapy should be administered only to those patients for whom the therapy being employed is of insufficient intensity.

The treatment of acute myelocytic leukemia in patients 30 years of age and younger.

The treatment of acute myelocytic leukemia in childhood and young adults has lagged behind that for acute lymphocytic leukemia. The studies described here were directed towards evaluating the role of intensive chemotherapy in the treatment of this illness. Intensive remission induction therapy combining cytosine arabinoside with an anthracycline antibiotic produced a complete remission rate comparable to that achieved in acute lymphocytic leukemia (45 of 49 patients or 92%).

Effects of partially thiolated polycytidylic acid and liposomes on in vitro colony-forming cells of leukemic mice.

Partially thiolated polycytidylic acid (MPC), an antileukemic agent, when administered to leukemic RF/UN mice inhibited the clonogenicity of bone marrow progenitor cells in a time- and dose-dependent manner. The effect of a single dose of MPC disappeared within 40 hr due to the rapid degradation of this compound in mice. When MPC was encapsulated in liposomes before injection, its activity at 19 hr after inoculation was similar to that of free MPC.

Macrophage differentiation of human precursor B-cell line by phorbol ester and colony-stimulating factor.

A human round cell line, KLM-2, is considered to be precursor B-cell by immunologic surface marker analysis and histochemical studies. The effect of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and/or colony-stimulating factor (CSF) on KLM-2 cells was investigated. KLM-2 cells became adherent to the bottom of the flask on day 2 after liquid culture with TPA, and the number of macrophage-like adherent cells (mAC) with pseudopodia showed a TPA dose-dependent increase to the peak level on day 3 or 4.

A pilot study of high-dose 1-beta-D-arabinofuranosylcytosine for acute leukemia and refractory lymphoma: clinical response and pharmacology.

1-beta-D-Arabinofuranosylcytosine (ara-C), 2 or 3 g/sq m, was administered as a 1-hr i.v. infusion every 12 hr for 10 or 12 doses to patients with acute leukemia and refractory lymphoma.

Comparison of agar and methylcellulose culture methods for human erythroid colony formation.

An agar culture method to permit human erythroid colony growth was described and was compared with the standard methylcellulose culture method. Although the cloning efficiency was greater and the colonies were larger in size in methylcellulose, the relative number of colonies was indistinguishable in the two culture systems after short-term exposure to cytosine arabinoside, adriamycin, tritiated thymidine, or busulfan. Thus, the agar culture system permits the growth of erythroid progenitor cells, which are at the same stage of differentiation as erythroid progenitor cells which can grow in methylcellulose.

Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia.

We studied 47 patients with sickle-cell anemia to determine the effect of alpha-thalassemia on the severity of their hemolytic anemia. We diagnosed alpha-thalassemia objectively by using alpha-globin-gene mapping to detect alpha-globin-gene deletions, studying 25 subjects with the normal four alpha-globin-genes, 18 with three, and four with two. The mean hemoglobin, hematocrit, and absolute reticulocyte levels (+/- S.

Relationship between plasma Ara-C and intracellular Ara-CTP pools under conditions of continuous infusion and high-dose Ara-C treatment.

Plasma level Ara-C and Ara-U in vivo and intracellular Ara-CTP pools in vivo and in vitro were measured using high-performance liquid chromatography and radioimmunoassay. Plasma Ara-C during High Dose therapy was found in two phases; one, a peak at t1/2 of approximately 5-8 minutes, the other approaching that of Continuous Infusion with a t1/2 of about 6 to 8 hours. There appears to be no relationship between peak levels of plasma Ara-C and intracellular Ara-CTP formed during High Dose therapy.

The effects of exposure to cytosine arabinoside upon the proliferation of leukemia colony forming units in vitro.

The sensitivity of leukemic colony forming units to exposure to cytosine arabinoside in vitro was measured for both acute myelocytic leukemia cells and for chronic myelocytic leukemia cells. There was significant variability in the sensitivity of the leukemic cells of different patients. By simultaneous measurement of the sensitivity of leukemic clonogenic cells to 3H-TdR one can distinguish between metabolic and cell cycle kinetic resistance to cytosine arabinoside.

Lack of erythroid burst-promoting activity in the media conditioned by eleven human T cell leukemia-lymphoma cell lines.

Eleven human T cell leukemia-lymphoma cell lines were tested to determine whether or not they released a product into their media which could stimulate erythroid colony formation by human peripheral blood mononuclear cells. None of the cell lines studied released erythroid burst-promoting activity detectable in our culture conditions.

Treatment failure in AML.

Emphasis on the reasons for successful therapy in the treatment of acute myelocytic leukemia (AML) has generally obscured the problem of treatment failures. This paper discusses failures in remission induction and relapse of leukemia. The contribution of patient-related factors as well as the heterogeneous characteristics of the leukemic cells are considered.

Comparison between agar and methylcellulose cultures of human leukemic cells.

A comparison was made between the agar and methylcellulose culture systems with respect to their ability to support the clonal growth of leukemic cells obtained from patients with acute myeloblastic leukemia, acute lymphoblastic leukemia, and chronic myelogenous leukemia in blastic crisis. The number of clusters and/or colonies formed and the morphology of the cells within them varied from patient to patient. Nevertheless, no significant difference between the two culture systems within given leukemic specimens was found.

Treatment of refractory adult acute lymphocytic leukaemia and acute undifferentiated leukaemia with an anthracycline antibiotic and cytosine arabinoside.

Ten patients with acute lymphocytic leukaemia (ALL) and four patients with acute undifferentiated leukaemia (AUL) in relapse or refractory to conventional therapy were treated with remission induction therapy consisting of an anthracycline antibiotic and cytosine arabinoside. Twelve patients had previously demonstrated resistance to vincristine-prednisone and nine patients had prior anthracycline therapy. Nine patients achieved complete remission after one course of therapy with a median time to remission of 30 d.

Clonal growth of leukaemic cells in vitro.

Human leukaemic cell specimens were obtained from patients and directly plated into soft agar (t = 0) or cultured for 1 week in liquid phase and then plated in soft agar. Growth for 1 week in liquid phase allowed the clonal growth in agar of leukaemic specimens which were unable to clone at t = 0. Clonal growth after liquid culture consisted of the usual leukaemic type of cluster-colonies, growth of a new type of 'syncytial' cell colony or a mixture of colony types.

Evaluation of the opsonic requirements for phagocytosis of Streptococcus pneumoniae serotypes VII, XIV, and XIX by chemiluminescence assay.

A luminol-enhanced chemiluminescence assay was used to investigate opsonic requirements for phagocytosis of STreptococcus pneumoniae serotypes VII, XIV, and XIX. After opsonization with whole immune sera (with antibody and total complement pathway), heat-inactivated immune sera (with antibody alone), or magnesium dichloride-ethylene glycol tetraacetic acid-chelated immune sera (with antibody and alternative complement pathway), live S. pneumoniae cells were incubated at 37 degrees C with normal polymorphonuclear leukocytes while serial chemiluminescence measurements were recorded.