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Biomedical subjects

E F Winton

Publications and source records attributed to E F Winton.

At least 73 records · Page 4Linked to original sources
PubMed1984

Transferrin in disease. I: A potential prognostic indicator in patients undergoing bone marrow transplantation.

Transferrin levels were measured immunochemically and the levels of several other plasma proteins were estimated by high resolution agarose gel electrophoresis in serial serum samples from nine patients undergoing bone marrow transplantation for aplastic anemia or leukemia. Three of five patients with low pretreatment transferrin levels died during initial hospitalization, and the other two suffered severe complications prior to recovery. All four patients with pretreatment transferrin levels within the normal range were discharged, three of them with minimal complications. Serial studies demonstrated that transferrin levels fell with the onset of infections or graft-versus-host disease and rose with recovery. Similar changes were not seen with any of the other plasma proteins measured. These results suggest that measurement of serum transferrin may reveal important prognostic information about patients undergoing bone marrow transplantation.

Adolescent↗
PubMed1984

A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial.

The Southeastern Cancer Study Group conducted a post-remission induction randomized trial in adult acute myelogenous leukemia to assess the efficacy of alternate drug therapy during consolidation and of immunotherapy during maintenance. Of 508 evaluable patients entered into the study, 335 (66%) achieved a complete remission treated with a 7-day infusion of cytosine arabinoside at a dose of 100 mg/sq m/day and 3 days of daunorubicin at a dose of 45 mg/sq m/day. Those in remission were randomized to receive 3 courses of 1 of 3 consolidation regimens: (A) a continuous infusion of 5-azacytidine, 150 mg/sq m/day for 5 days; (B) 5-azacytidine plus beta-deoxythioguanosine, 300 mg/sq m/day for 5 days; or (C) cytosine arabinoside, 100 mg/sq m/day intravenously, and thioguanine, 100 mg/sq m orally every 12 hr, plus daunorubicin, 10 mg/sq m every 24 hr daily for 5 days. There was no difference in relapse rate among the 3 arms. Those completing consolidation and remaining in remission were randomized to 1 of 3 maintenance regimens: (D) chemotherapy, 5-day infusion of cytosine arabinoside and 2 days of daunorubicin (same doses as induction) given every 13 wk for 1 yr; (E) BCG given twice weekly for 1 mo and then monthly for 1 yr; or (F) the combination of regimens D and E. The median duration of remission was significantly better on regimen D (17.4 versus 9.4 and 9.5 mo), and median survival was 29 mo compared to 21 mo for the other regimens. Those given different drugs during consolidation than used for induction (regimens A and B) and subsequent chemotherapy for maintenance (regimen D) had the longest remission durations and survival. Immunotherapy was not as good as intensive chemotherapy for maintenance.

Adolescent↗
PubMed1984

A morphologic and immunologic study of the large granular lymphocyte in neutropenia with T lymphocytosis.

We report four patients with expansion of a unique population of lymphocytes that is consistently associated with neutropenia. Two patients also had rheumatoid arthritis and autoantibodies. The lymphocytes contained many cytoplasmic azurophilic granules, which possessed strong acid phosphatase activity. Multiple cytoplasmic parallel tubular arrays were observed ultrastructurally. These granular lymphocytes showed the T suppressor/cytotoxic cell phenotype (E+, OKT3+, OKT8+, OKT4-, OKM1-, OKI1-) and exhibited antibody-dependent cell-mediated cytotoxic activity but little or no natural killer cytotoxicity. They did not respond to recall antigens, concanavalin A, or pokeweed mitogen, but the cells from one patient did respond to phytohemagglutinin. No in vitro suppressor cell activity on mitogenic responses of allogeneic cells and on mixed lymphocyte cultures could be demonstrated. There was no evidence of suppression of immunoglobulin synthesis in vivo. It is uncertain that the expansion of this subset of lymphocytes represents a leukemic process. Their constant association with neutropenia, however, raises the possibility that the increase in large granular lymphocytes and neutropenia might be pathogenetically related.

Adult↗
PubMed1984

The effect of alkyl-lysophospholipids on tritiated thymidine incorporation and clonogenicity in vitro of normal and leukemic human cells.

Alkyl-lysophospholipids are analogues of 2-lysophosphatidylcholine which have been reported to have selective antitumor activity. A survey of the in vitro activity of racemic 1-octadecyl-2-methoxy-glycero-3 phosphorylcholine on in vitro clonogenicity in soft agar and tritiated thymidine incorporation was conducted on bone marrow specimens from a series of patients with acute myelogenous leukemia (AML) and chronic myelocytic leukemia (CML) and hematologically normal individuals. A dose- and time-dependent inhibition of colony formation and thymidine incorporation was observed in the normal and leukemic specimens. No selective effect of the compound could be demonstrated under the conditions employed in these studies.

Bone Marrow Cells↗
PubMed1983

The clonogenic assay as a reproducible in vitro system to study predictive parameters of treatment outcome in acute nonlymphoblastic leukemia.

Seven institutions studied the cloning pattern of leukemic cells from pretherapy bone marrows of 273 patients with newly presenting and relapsed acute nonlymphoblastic leukemia. The cloning assay was done in all centers using an identical double-layer agar method with a common source of colony-stimulating factor. Cells were incubated for seven days, and clones were identified visually with an inverted microscope. All centers were able to obtain clonal growth in a substantial proportion of patients. Differences in growth pattern were observed between the major contributing center and the pooled results for all other centers. However, an analysis of clinical results suggested that in vitro differences were more likely related to differences in the patient populations than to variability in laboratory technique. The proportion of marrows in which leukemic cells formed colonies (greater than 40 cells) and large clusters (20-40 cells) was greater in relapsed patients than in newly presenting patients (P less than .06). A progressive improvement in induction treatment outcome was seen with decreasing clonal growth. Patients whose marrows did not produce clones had a complete remission (CR) rate of 83% versus 50% for those patients whose marrow leukemic cells formed colonies and/or large clusters (P = .05). In vitro drug sensitivity studies with cytosine arabinoside and adriamycin were performed on bone marrow cells of patients treated with this combination clinically. The percent killing of clonogenic cells in this assay correlated with remission induction outcome. Complete remission was obtained in 73% of 15 patients whose bone marrow leukemic cells showed greater than 30% killing by in vitro drug exposure, and CR was obtained in only 30% of 23 patients whose marrows showed less than 30% killing (P less than .01). The results indicate that the clonogenic assay correlates with treatment outcome and can be used for drug sensitivity testing in patients with acute nonlymphoblastic leukemia. The limitations of the assay are discussed.

Acute Disease↗
PubMed1983

Autologous marrow transplantation after karyotypic conversion to normal in blastic phase of chronic myelocytic leukemia.

A patient with blastic transformation of Philadelphia chromosome-positive chronic myelocytic leukemia was treated with acridinyl anisidide, which resulted in conversion to a normal karyotype. At that time, bone marrow was harvested and cryopreserved. After relapse, the patient was treated with cyclophosphamide and fractionated total body irradiation followed by autologous marrow transplantation. Serial karyotypes and blood counts, determined up to 14 months after transplantation, remained normal.

Bone Marrow Transplantation↗
PubMed1983

Amsacrine in refractory adult acute leukemia: a pilot study of the Southeastern Cancer Study Group.

A phase II pilot study of amsacrine in refractory adult acute leukemia was conducted by the Southeastern Cancer Study Group from May 1979 to August 1980. Amsacrine, 90 mg/m2, was given daily for 5-8 days to 45 patients with acute myeloblastic leukemia, 15 patients with acute lymphoblastic leukemia, and six patients with blastic transformation of chronic granulocytic leukemia. Of the 66 patients entered in the study, 59 (89%) were evaluable for response. Complete remissions were observed in eight of 41 evaluable patients with acute myeloblastic leukemia (20%) and in three of 12 with acute lymphoblastic leukemia (25%). Remissions were short-lived (median, 7.9 weeks; range, 2-27). Toxic effects included the expected myelosuppression (100%), as well as moderate to severe stomatitis (46%), hyperbilirubinemia (30%), and supraventricular tachycardia (1.5%). This cooperative group pilot study confirms previous reports from single institutions that amsacrine is a useful drug in the treatment of refractory adult acute leukemia and is worthy of further study.

Adolescent↗
PubMed1983

Acute tumor lysis in T-cell leukemia induced by amsacrine.

The acridine orange derivative amsacrine (National Services Center No. 249992) was used to treat a patient with T-cell acute lymphoblastic leukemia (ALL). A 17-year-old boy had a tumor lysis syndrome after a single 200 mg/sq m dose of amsacrine. This was followed by a prolonged period of marrow hypoplasia leading to death from infection. Review of the literature and our own experience would suggest that T-cell ALL may be exquisitely sensitive to amsacrine.

Adolescent↗
PubMed1982

Influence of quantity of granulocytes transfused on response.

Data from 165 infectious &/or febrile episodes in granulocytopenic patients given granulocyte transfusions wee reviewed to determine what factors influenced clinical outcome and if there was any correlation between clinical improvement and dose of granulocytes given. Factors not related to granulocyte dose that influenced survival and clinical improvement included sex, the type of infecting organism and marrow recovery during the 3 weeks after the initiation of granulocyte transfusions. Patients infected with organisms other than Pseudomonas, females and those whose marrows recovered all had a significantly higher frequency of clinical improvement and survival. All 52 patients with marrow recovery survived the 21-day study period and 94% improved compared to only 59% survival and 48% improvement in those whose marrows did not recover. This observation indicates granulocyte transfusion therapy is a poor substitute for normal granulopoiesis.

Adolescent↗
PubMed1981

In vitro studies of lactoferrin and murine granulopoiesis.

Human lactoferrin (LF) has been reported to inhibit in vitro granulopoiesis by means of decreasing colony-stimulating activity production by monocytes. We performed a series of experiments to determine if the reported experimental results could be replicated using highly purified murine LF and murine target cells. Three different types of experiments were performed. (1) Medium was conditioned by lung, femoral shaft, and adherent peritoneal cells in the presence and absence of LF, and the granulopoietic stimulating activity in the conditioned media was assayed by means of a 7-day agar colony assay and a 3-day liquid slide chamber assay, which quantitates 3H-TdR incorporation into DNA. (2) In cultures stimulated by an underlayer of adherent peritoneal cells, marrow cell colony formation in agar was determined after 7 days of culture in the presence or absence of LF. (3) LF was added to 3-day liquid marrow cell cultures that had been stimulated by lung or femoral shaft conditioned media. In all experimental situations, highly purified, iron-saturated LF in concentrations up to 10(-7) M had no effect on in vitro granulopoiesis. These results do not support LF's reputed regulatory role in granulopoiesis.

Animals↗