Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty-seven patients with refractory acute leukemia were treated with high-dose cytosine arabinoside to establish the maximum tolerated dose and duration and to determine the antileukemic activity. The maximum tolerated regimen was found to be 3 g/sq m every 12 hr for 6 days. At this dose, nonhematologic toxicity was limited to conjunctivitis in approximately half of the patients, and liver toxicity (transient elevations in transaminase, alkaline phosphatase, or bilirubin) was frequently observed, but neither was dose-limiting. Extending the duration of treatment to 8 days resulted in excessive diarrhea and skin toxicity (painful erythema with bullae), while increasing the dose to 4.5 g/sq m q. 12 hr for 6 days resulted in severe cerebellar toxicity. Myelosuppression was severe, but was not related to the intensity of treatment; granulocyte recovery occurred a median of 28 days (range 22-40 days) after initiating therapy, and platelet recovery occurred after a median of 25 days (range 16-41 days). Antileukemic activity was evaluable in the 46 patients who survived at least 3 wk. Complete remissions were obtained in 1 of 6 patients with chronic myelogenous leukemia (CML) in accelerated phase and 1 of 3 acute lymphoblastic leukemia (ALL) patients. A more detailed analysis of response was possible for the 37 evaluable patients with acute nonlymphoblastic leukemia: 70% of these patients responded, with 51% complete remissions. The median unmaintained response was 4 mo (range 2-26+ mo). The complete response rate was higher in patients who received at least 12 doses of high-dose cytosine arabinoside compared to shorter regimens [17/28 (61%) versus 2/9 (22%), p less than 0.05]. Resistance to cytosine arabinoside in conventional doses was documented in 11 patients, 5 of whom responded (2 complete remissions) to high-dose regimens. We conclude that high-dose cytosine arabinoside in the maximally tolerated regimen of 3 g/sq m every 12 hr for 6 days has substantial antileukemic activity in patients refractory to standard therapy. Durable unmaintained remissions can be achieved, even in patients who fail to respond to cytosine arabinoside in conventional doses.
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PMID:High-dose cytosine arabinoside therapy for refractory leukemia. 622 74

Leukocyte transfusions from patients with chronic myelogenous leukemia (CML) and elevated WBC counts were given to 14 patients with acute leukemia for the treatment of 16 infectious episodes. The WBCs were not irradiated to determine if engraftment with production of granulocytes would occur following infusion of immature myeloid elements. No recipient was alloimmunized by clinical and serologic criteria. High leukocyte yields were obtained using a variety of differential centrifugation techniques with a mean WBC yield/transfusion of 95 X 10(9) (range 19-275). A mean of 2.5 transfusions (range 1-11) were administered/recipient with a mean total dose of 235 X 10(9) WBC/transfusion episode (range 50-590). Seven patients had granulocyte counts greater than 500/microliters for four or more days (range 4-11 days) following the last transfusion. Ph1 chromosomes were documented in 2 of 4 patients tested 2-8 days following transfusion. Leukocyte alkaline phosphatase scores were increased (greater than 150) in 5/5 recipients tested post-transfusion demonstrating that production of this enzyme can be induced in CML granulocytes. Except for one severe transfusion reaction, there were no significant side effects and no recipient developed signs of graft versus host disease. All patients with sustained increments demonstrated rapid clinical improvement including 3 severely infected, poor risk patients undergoing initial induction therapy. These 3 patients all achieved complete remission with no evidence of the Ph1 chromosome. Because of the high dose of WBC which can be collected and the salutary effect of continued leukocyte production, CML WBC may be the preparation of choice for selected, non-alloimmunized, severely infected patients.
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PMID:Sustained post-transfusion granulocyte count increments following transfusion of leukocytes obtained from donors with chronic myelogenous leukemia. 657 31

To study the relationship granulocyte alkaline phosphatase (AP)--zinc (Zn) in mixed leukocyte suspensions, the enzyme from 51 mixed leukocyte suspensions was separated and purified. In the pure extract, determinations were carried out for enzymatic activity--using the autoanalyzer LKB 8600--and for Zn content--using atomic absorption spectrophotometry. From the data obtained it resulted that, in agreement with the results in the literature Zn concentration in the mixed leukocyte suspensions from chronic myeloid leukemia, (CML) patients is about half that in the normal controls (0.65 +/- 0.15 as compared with 1.24 +/- 0.15 micrograms/mg total nitrogen). Granulocyte AP separated from normal leukocyte suspensions was found to bind about 95% of the total Zn content, i.e., 1.21 +/- 0.15 micrograms/mg total nitrogen and its enzymatic activity was about 16 U/g total nitrogen. In CML patients the enzyme bound a mean Zn concentration of 0.55 +/- 0.15 micrograms/mg total nitrogen and its mean activity was 2.25 U/g total nitrogen, i.e., about 86% of the normal values found in the controls. The enzymatic activity decreased to zero after only 20 min dialysis with 8-hydroxyquinoleine-5-sulfonic acid (8HC5S) as compared with the 60-80 min in the controls. It can be concluded that the leukemic leukocyte is unable to form the metal-enzyme complex owing to the deficit of the Zn involved in the enzymatic activity.
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PMID:The relationship zinc--alkaline phosphatase activity in normal and pathologic granulocytes. 658 74

Leucocyte alkaline phosphatase (LAP) is a granulocyte enzyme whose concentration varies in disease states. In order to determine whether the pattern of expression is altered in leukaemic granulocytes, we have analysed the LAP isozyme pattern of a series of normal subjects and patients with various haematological diseases. Electrophoretic patterns of partially purified LAP samples were determined by polyacrylamide gel electrophoresis in the presence of Triton X-100. These patterns were reproducible on repeated samples from the same patient. Presence of the LAPf and LAPs isozymes were determined after staining with the dye Fast Blue BB. Granulocytes were obtained from 15 normal subjects. Thirteen of these samples had only the LAPs isozyme. The other two had LAPs, plus a small amount (less than or equal to 10% of total) of LAPf activity. Eight patients with stable phase chronic myelogenous leukaemia (CML) had only small amounts of the normal LAPs isozyme and no evidence of LAPf . Of 11 patients with CGL who clinically had blast crisis. 10 had both LAPs and LAPf . The eleventh patient who was Ph1 negative had only LAPs. Three of five patients with polycythaemia vera had only the LAPs isozyme while two had both isozymes. Six patients with non-malignant leucocytosis had only LAPs. We interpret this data to indicate that the increased levels of LAP activity in some CGL blast crisis patients are primarily related to synthesis of the LAPf isozyme.
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PMID:Altered isozyme patterns of leucocyte alkaline phosphatase in disease states. 658 2

A 44-year-old woman with Ph1-positive CML achieved a complete remission following small doses of MCNU. She is still in remission after more than 18 months without maintenance therapy. Chromosomal analyses revealed Ph1 chromosomes in 100% of cells before the therapy, and a mosaic of Ph1-positive cells (74%) and negative cells (26%) after the therapy. Leukocyte alkaline phosphatase scores were low before the therapy and became normal after the therapy. MCNU seems to be an effective drug for treating CML producing prolonged remission with reappearance of Ph1-negative normal clones in the present case.
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PMID:[Prolonged remission in a patient with chronic myelocytic leukemia (CML) by methyl 6-[3-(2-chloroethyl)-3-deoxy-alpha-D-glucopyranoside (MCNU)]. 659 76

Granulocyte alkaline phosphatase (GAP) was extracted from the leukocyte suspensions of 15 subjects with chronic myeloid leukemia (CML), determining the Zn content by atomic absorption spectrophotometry. The purified enzymatic preparation was dialyzed against a ZnCl2 solution (.01 mg%) in TRIS-HCl 0.1 M, pH 7.5, for 48 hours. After dialysis Zn concentration and GAP activity reached normal values. This suggests that the GAP molecule isolated from CML subjects is not altered as it is able to receive at most 2 Zn moles responsible for the enzymatic function.
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PMID:Alkaline phosphatase activity improved by the addition of zinc in granulocytes from leukemic subjects (in vitro study). 659 61

Clinical and laboratory findings at the time of diagnosis were correlated with the survival of 242 patients with chronic myelocytic leukemia. Twelve patients with the blastic stage of the disease (blasts greater than or equal to 29%) had a median survival of eight months. Of the nonblastic patients, 28 without the Philadelphia chromosome had a relatively constant mortality averaging 43% per year and a median survival of 13 months, markedly worse than the Ph1-positive group (mortality, 6% in the first year, 17% in the second year, and the 25% per year, with a median survival of 43 months; P less than 0.001). In the latter group of 202 patients, features reflecting the "quantity" of leukemia (leukocyte count, marrow cellularity, and M:E serum B12, different degrees of splenomegaly, presence or absence of symptoms) had weaker or short-term correlations with mortality, while "qualitative" abnormalities (e.g., increased percentage of circulating blast, extramedullary leukemic tumors, major abnormalities of erythropoiesis or platelet production, marked basophilia or eosinophilia) had strong and persistent correlations with mortality. Chromosome abnormalities in addition to the Ph appeared to have a delayed though significant effect on survival. Serum alkaline phosphatase and SGOT levels did not correlate significantly with survival, but major elevations of serum LDH were associated with increased mortality throughout the course of the disease.
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PMID:Prognostic features at diagnosis of chronic myelocytic leukemia. 694 41

Cytogenetic studies were made on 160 patients with acute nonlymphocytic leukemia (ANLL) between 1963 and 1979, of whom 115 had acute myelocytic leukemia with 67 patients showing aneuploidy (58.3%). Among these, 24 patients were found to have similar chromosome alterations that appeared to involve specifically chromosomes 8 and 21. Banding studies on at least 7 of these patients confirmed the presence of a translocation between these two chromosomes. Of 160 ANLL patients, 142 were scored for neutrophil alkaline phosphatase (neutrophil AP) at the time of diagnosis. Fifty-nine patients showed a low neutrophil AP score, 42 a normal value, and 41 a high value. All patients with 8;21 (or C/G) translocation had a low neutrophil AP score and leukemic cells with maturation (M2 of FAB classification) in the bone marrow. In vitro liquid culture for 2 wk of 8;21 translocated leukemic cells revealed no increase of neutrophil AP activity nor increase of mature granulocytes, whereas 9;22 translocated chronic myelocytic leukemia cells with a low neutrophil AP score did so. Neutrophil AP score at the time of diagnosis in acute myelocytic leukemia is very useful for detecting 8;21 translocation AML and for studying the pathophysiology and genetic alterations of the characteristic subgroup of AML with 8'21 translocation.
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PMID:In vivo and in vitro activity of neutrophil alkaline phosphatase in acute myelocytic leukemia with 8;21 translocation. 694 48

We describe two patients who had similar features of erythrocytosis and marked leukocytosis but who were subsequently classified as having chronic myelogenous leukemia and polycythemia vera, respectively, using leukocyte alkaline phosphatase scores and cytogenetic studies to detect the Philadelphia chromosome. The patient diagnosed as having polycythemia vera had a leukocyte count of 164,000/cu mm, which remained at similar levels when the patient was not in remission. We believe this is the first well documented case of PV with a leukocyte count above 150,000/cu mm.
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PMID:Erythrocytosis and marked leukocytosis in overlapping myeloproliferative diseases. 695 6

A possible correlation between Fc-IgG receptor expression and neutrophil alkaline phosphatase (NAP) activity was investigated in relation to maturation of granulocytes in human peripheral blood and bone marrow. NAP activity was studied in bone marrow from patients with normal peripheral blood NAP scores (20-100) and compared with those with high NAP scores. Results indicate that NAP activity is confined to segmented neutrophils (SN) in marrow and peripheral blood except when peripheral NAP activity is abnormally high. There is a normal increase of approximately 60% in mean NAP scores of peripheral blood compared to marrow SN. Granulocyte Fc-IgG receptor activity, known to increase with maturation, was studied in relation to NAP activity. A combined assay using a rosetting technique with ox-erythrocyte (oxE) antibody-IgG and subsequent NAP cytochemistry was used. Receptor expression was found to be virtually complete in normal granulocytic maturation before the appearance of detectable NAP activity. This was supported by findings in chronic myeloid leukaemia where no cases of low Fc receptor activity were found despite NAP scores of less than 5. The significance of these findings is discussed in the light of current concepts of the control of NAP activity.
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PMID:Relation of neutrophil alkaline phosphatase activity to Fc IgG receptor development in human blood and bone marrow. 695 85


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