Chronic Granulocytic Leukemia Patients Research Articles

Profile of blood coagulation and fibrinolysis in chronic myeloproliferative disorders.

Blood coagulation and fibrinolysis were studied in 65 patients with chronic myeloproliferative disorders (MPD). They consisted of 28 patients with chronic granulocytic leukemia (CGL) in chronic phase, 7 with CGL in blast crisis, 9 with polycythemia vera (PV), 13 with primary thrombocythemia (PTh) and 8 with primary myelofibrosis (MF). Hemorrhagic and thrombotic complications were observed in 19 and 8 patients, respectively. Activated partial thromboplastin time and prothrombin time were prolonged in many patients. Low factor II levels were observed in some CGL patients. Factor V was decreased in CGL patients in chronic phase and in PV patients. Fibrinogen was either normal or increased in most patients, but an elevation of fibrin/fibrinogen degradation products (FDP) was found in some patients. The VIIIR: Ag/VIII:C ratio was increased in CGL patients in blast crisis, in PV patients and in PTh patients. Antithrombin III and plasminogen were below normal in some patients. Most patients showed a decrease in alpha 2-plasmin inhibitor. These findings suggest that blood coagulation and fibrinolysis are involved in the pathogenesis of the thrombotic and hemorrhagic complications in these patients. Chronic low-grade intravascular coagulation might be present in some patients with MPD.

Defective Hydrogen Peroxide Production in Chronic Granulocytic Leukaemia Neutrophils

Hydrogen peroxide (H2O2) production by polymorphonuclear neutrophils (PMN) during phagocytosis was fluorometrically vestimated over an incubation period of 80 min during which dead Candida guilliermondii were ingested. Ten patients with chronic granulocytic leukaemia (CGL) were tested and compared with 15 normal subjects. The production of H2O2 by CGL neutrophils was about 29% of normal. There was no correlation between H2O2 production and the impaired killing of Candida guilliermondii by the neutrophils of CGL patients.

Nonrandom chromsome rearrangements in 27 cases of human myeloid leukemia

The R-banding pattern of the chromosomes of 31 patients hospitalized in the Hematologic Clinic for myeloid leukemia were studied before chemotherapy. This analysis permitted identification of one unusual 3-chromosome rearrangement t(3;9;22) in addition to 25 classic forms of (22q-;9q+) translocation accompanied by the specific Ph' chromosome in chronic granulocytic leukemia patients, independent of the blastic course of the disease. During blastic crisis observed in 6 patients, extra 8 and 10 chromosomes, monosomy for chromosome 17, isochromosomes 17q, translocation (12q;13q), and additional Ph' were noted. The nonrandomness of these findings is determined from results published by other authors. Their significance for the cellular phenotype is presently unknown.

Chronic granulocytic leukemia without the Philadelphia chromosome.

Cytogenetic studies of bone marrow were performed in 230 consecutive cases of patients with chronic granulocytic leukemia (CGL) admitted to the National Cancer Institute since 1961. Twenty patients lacked the Philadelphia (Ph1) chromosome. All were previously untreated. When compared with Ph1-positive patients, CGL patients with Ph1-negative disease had a higher median age (60 compared with 42 years) and were diagnosed at lower median leukocyte (75,000) and platelet counts (170,000). Their response to chemotherapy was generally poor, with a median survival of 15 months compared with 44 months for the Ph1-positive group. Four patients survived more than 5 years and two, more than 10 years. Thirty-five per cent of the Ph1-negative patients had aneuploid cell lines of various percentages. Absence of the Ph1 chromosome in patients with the hematologic characteristics of CGL is a bad prognostic sign.

Relationships between membrane antigens of human leukemic cells and oncogenic RNA virus structural components.

Leukemic cells from all human chronic granulocytic leukemia (CGL) and some acute myelomonocytic leukemia (AMML) donors are lysed by rabbit antisera to a purified glycoprotein of Friend murine leukemia virus (FLV gp71) in a microcytotoxicity assay. These antisera are not cytotoxic to cells from patients with acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or to peripheral blood lymphocytes from normal donors. A goat antiserum to gradient purified FLV in addition to reacting with cells from CGL and AMML donors also reacted with cells from AML patients and some ALL donors. However, this antiserum failed to react with cells from CLL patients. Peripheral blood and bone marrow leukocytes prepared from leukemic patients in clinical remission failed to react with antisera to FLV and FLV gp71. Absorption experiments demonstrated that the antigen on CGL cells which is reacting with the antiserum to FLV gp71 is also present on normal human platelets and neutrophils. Similar absorption studies showed that the antigen on AML cells detected by the FLV antiserum is not present on normal leukocytes and platelets and appears to be related to the major internal p30 antigens of mammalian RNA tumor viruses. Another antigenic relationship between oncornaviruses and membrane antigens of human leukemia cells was shown by the ability of FLV antigens to absorb the cytotoxic reactivity of nonhuman primate antisera detecting human leukemia-associated antigens. FLV and FLV gp71 antigens were able to absorb all cytotoxic activity of monkey and chimpanzee antisera to human myeloid leukemia antigens when these antisera were tested with CGL cells. These two approaches to an analysis of cross-reactivity indicate that the antigenic determinant(s) detected by the cytotoxic reactions of the FLV gp71 antiserum with human CGL cells is different from the determinant on FLV gp71 which is responsible for the inhibition of the reactivity of simian antisera with CGL cells. Since the goat and rabbit antisera to FLV and FLV gp71 are able to distinguish AML from CGL cells by direct cytotoxicity testing and absorption, they may be valuable reagents for the serological diagnosis of myeloid leukemia. In addition, since peripheral blood cells from AML and CGL patients in clinical remission were seronegative, the antisera may be valuable as management aids. The data in this report indicates that whatever the mechanism of leukemogenesis is in man, cells from CGL and AML patients possess certain membrane antigens which cross-react with FLV structural components such as p30 and gp71.

Phagocytic function of leucocytes from patients with acute myeloid and chronic granulocytic leukaemia.

Summary. The capacity of peripheral blood leucocytes from 11 patients with acute myeloid leukaemia (AML) and 10 patients with chronic granulocytic leukaemia (CGL) to ingest and kill Candida albicans was tested in vitro. The patients with CGL were, for the most part, receiving chemotherapy and had peripheral leucocyte counts in the normal range, whereas none of the patients with AML had received therapy within the preceding 7 days and none had entered complete remission. Ingestion of Candida organisms was found to be normal in both groups of patients, but the killing activity (candidacidal index) of leucocytes from patients with AML was significantly impaired. Leucocytes from CGL patients killed engulfed Candida normally. It is postulated that the candidacidal defect in leucocytes from patients with AML has two components, one intrinsic to the leucocyte and the other due to a deficient (or inhibitory) factor in the patient's plasma.

Autopsy study of leukemia in atomic bomb survivors, Hiroshima-Nagasaki, 1949–1969

Four hundred and seventy-four leukemia autopsies collected from 1949 to the end of 1969 at the Atomic Bomb Casualty Commission (ABCC) in Hiroshima and Nagasaki were studied in relation to dose of radiation at the time of bombing (ATB) using tentative 1965 dose estimates. The leukemia rate was based on autopsy cases belonging to the fixed Life Span Study (LSS) sample and was examined by dose for the period October 1950 to December 1969. There were 61 leukemia cases in 3,959 autopsy cases in this sample. The rate increased by dose, especially in those exposed to more than 100 rads for both 1950–1960 and 1961–1969, even though the autopsy rates differed between these two periods. The pathologic findings were compared by dose for 361 leukemia cases who were born before the bomb including the 61 patients in the LSS sample. Pathologically, no individual leukemia autopsy could be differentiated and designated as being radiation-induced in this study. No case of chronic lymphocytic leukemia was detected among cases receiving 1 rad or more. No statistically significant difference related to radiation dose was found in acute leukemia and chronic granulocytic leukemia for various pathologic changes, except for the less intense infiltration of leukemic cells in the lungs of chronic granulocytic leukemia patients.

METABOLISM OF 9-ETHYL-6-MERCAPTOPURINE BY HUMANS.

Evidence was presented that 9-E-6-MP is dealkylated by the human in amounts adequate to provide enough 6-MP to explain the effectiveness of this drug when it is administered to chronic granulocytic leukemia patients. 9-E-6-MP does not serve as substrate for xanthine oxidase, nor purine nucleoside phosphorylase. The possibility that the enzyme responsible for dealkylation is present in human bone marrow or neutro-phils is discussed.

The Threshold Dose of P32 for Leukemic Cells of the Lymphocytic and Granulocytic Series

Abstract Analyses of the threshold dose of P32 to control 201 chronic lymphocytic leukemia patients and 100 chronic granulocytic leukemia patients and of the P32 dose to maintain 133 chronic lymphocytic leukemia patients for a mean period of 50.2 months and 49 chronic granulocytic leukemia patients for a mean period of 33.6 months are analyzed. These threshold doses fit the logarithmic probability distributions given in the tables and figures. See PDF for Figure See PDF for Figure When the dose in mc. to control was plotted against the leukocyte count, a straight line was obtained on log log paper. The equation for this curve for the median dose to control chronic granulocytic leukemia is: log mc. P32 per 12 weeks = 0.33 log L - 0.633, where L is the leukocyte count on the day the first P32 was given. The equation for the log log curve relating median dose to control chronic lymphocytic leukemia to initial counts above 15,000 is: log mc. P32 per 12 weeks = 0.47 log L - 1.420. But the 40 aleukemic or subleukemic cases with leukocyte counts below 15,000 had a median P32 requirement and standard deviation that did not differ significantly from that for the entire group, suggesting that this subleukemic group includes patients resembling the entire spectrum of cases with elevated initial leukocyte counts. See PDF for Figure See PDF for Figure The median dose of P32 per year to maintain chronic granulocytic leukemia cases fits the equation: log P32 per year = 0.546 log L - 1.506, and the corresponding equation for chronic leukemic lymphocytic leukemia is: log mc. P32 per year = 0.45 log L - 1.22. The group of lymphocytic leukemias with initial counts below 15,000 again showed a median and distribution similar to that for the entire leukemic group. The remarkable fact that the dose requirement years later is related to the initial leukocyte count is discussed. Revised recommendations on dosage schedule for titrated, regularly spaced P32 therapy of the chronic leukemias are presented. For each individual patient with chronic leukemia, there is a threshold dose of intravenously administered P32 below which no effect is observed. The dose and interval which will maintain a uniform leukocyte count of about 15,000 may remain unchanged for years or may show abrupt changes at any time to either a lower or higher requirement.

Vitamin B12 binding capacity of normal and leukemic sera.

Abstract A method for the measurement of binding capacity of serum for vitamin B 12 is described. With this method, sera from normal subjects and patients suffering from chronic granulocytic leukemia, lymphocytic leukemia (acute or chronic), and various other conditions were studied. The serum of chronic granulocytic leukemia patients showed an increase and that of lymphocytic leukemia patients a decrease of the binding capacity for vitamin B 12 .