Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients with acute lymphoblastic leukemia and one with lymphosarcoma cell leukemia developed transient hypofibrinogenemia during a course of treatment with vincristine and prednisone. There was no evidence of overt, disseminated intravascular coagulation or significant liver impairment. Fibrinogen survival using homologous-125-I-labelled fibrinogen was measured in two patients; it was moderately shortened in both, perhaps indicating subclinical intravascular coagulation. Rapid lysis of leukemic cells might have been responsible for activating coagulation and fibrinolysis in vivo. These four patients, however, were not different in any clinical or laboratory parameter from nine others with lymphoblastic leukemia similarly treated and investigated without observing any defect in their fibrinogen. There were no bleeding complications and the fibrinogen level became normal within 13 to 30 days.
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PMID:Hypofibrinogenemia associated with vincristine and prednisone therapy in lymphoblastic leukemia. 105 92

Blood coagulation, fibrinolytic and unspecific proteolytic parameters were investigated in 34 patients with acute myeloid leukemia. An increased activity of the coagulation system, documented by elevated thrombin-antithrombin III-complex (TAT) plasma levels, was found in 91% of the patients; 50% had increased elastase plasma levels. Hyperfibrinolysis, as shown by elevated fibrin split-product D-Dimer plasma levels, was detected in 91% of AML patients. Activation of these enzyme systems was not associated with relevant defects in blood coagulation or fibrinolysis in the majority of the patients investigated. In selected cases of promyelocytic M3 and monoblastic M5 leukemia, however, hypofibrinogenemia and alpha 2-plasmininhibitor deficiency was found, most likely due to depletion of these proteins in the course of disseminated intravascular coagulation and secondary hyperfibrinolysis. Significant correlations were calculated between TAT and fibrinogen (r = -0.57, P less than 0.005), TAT and D-Dimer (r = 0.89, P less than 0.0005), and D-Dimer and alpha 2-plasmininhibitor (r = -0.77, P less than 0.0005) levels. Indications of a pathogenetic importance of primary hyperfibrinolysis or unspecific proteolysis for hypofibrinogenemia and alpha 2-PI deficiency were not found.
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PMID:Hemostatic and fibrinolytic parameters in patients with acute myeloid leukemia: activation of blood coagulation, fibrinolysis and unspecific proteolysis. 227 76

We examined fibrinolytic substances in homogenate of leukemic cells, normal granulocyte or mononuclear cells fraction. Plasminogen activators (PA) were significantly low in normal cells, but they were slightly increased in lymphoblastic leukemia cells and markedly increased in myeloblastic leukemia cells. In almost leukemic cells homogenate, the antigen ratio of tissue type PA (t-PA)/urokinase type PA (u-PA) was about 2.0. In especially AMMoL and AMoL, PA activity had discrepancy between euglobulin lysis time and amidolytic assay using chromogenic substrate. As PA inhibitor (PAI)-II was markedly increased in them. PAI might effect the PA assay. PA activity of leukemic cells homogenate was similar to that without t-PA stimulator and leukemic cells homogenate significantly stimulated t-PA. As both PA activity and antigen were statistically increased in leukemic cells homogenate of patient with disseminated intravascular coagulation (DIC), PA and PA stimulator in leukemic cell might play an important role in hypofibrinogenemia or DIC.
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PMID:[Plasminogen activator in leukemic cell homogenate]. 228 63

We report here a patient with acute lymphoblastic leukemia (ALL) in whom hypofibrinogenemia developed during chemotherapy. The patient was a 65-year-old female who was diagnosed as having common ALL, and she was treated with BHAC-DMPV (enocitabine: 160 mg, daunorubicin : 40 mg, 6-MP: 35 mg, prednisolone (PSL): 60 mg, and vincristine: 2 mg). Hypofibrinogenemia appeared promptly each chemotherapy, including PSL was given. To ascertain a correlation between hypofibrinogenemia and the drugs given in this patient, a trial administration of PSL was attempted during a complete remission state. The level of fibrinogen, in terms of the amount of antigen or coagulability, decreased during PSL treatment, although the levels of AT III, plasminogen, alpha 2PI.Plm complex, and FDP did not change. Thus, it is difficult to speculate that PSL induced destruction of leukemia cells and release of protease from the cells resulting in fibrinolysis and hypofibrinogenemia in this case. These findings also suggest that the administration of only PSL could induce hypofibrinogenemia.
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PMID:[Transient hypofibrinogenemia induced by prednisolone in a case of acute lymphoblastic leukemia]. 268 81

Sparsomycin is a cytotoxic drug exhibiting a broad spectrum of in vitro activity against murine tumors and many tumor cell lines. It also appears to be a potent stimulator of the antitumor activity of cisplatin against L1210 leukemia in vivo. However, because of its toxicity, the antitumor activity of sparsomycin on murine tumors in vivo has been disappointing. The purpose of our study was to investigate the pharmacokinetics of this drug as well as the possible mechanisms that produce sparsomycin toxicity. Tests on beagle dogs revealed that about 60% of the drug is eliminated by metabolic clearance, while 40% is eliminated by the kidneys. After a single bolus injection of 0.1 mg/kg sparsomycin without narcosis, sparsomycin was eliminated with a t beta 1/2 of 0.6-0.7 h, the AUC being 0.32-0.38 mg.h.l-1, and the volume of distribution (Vd) 0.26 l/kg. In addition to being subject to glomerular filtration, sparsomycin is probably also actively excreted and actively reabsorbed by the renal tubuli. Sparsomycin itself may inhibit its active tubular excretion, thus resulting in a decrease in the drug's renal clearance and its accumulation in the plasma. Sparsomycin appeared to be toxic primarily in the liver, disturbing its function and the synthesis of plasma proteins. Two out of five dogs developed hemorrhagic diathesis due to hypofibrinogenemia and deficiency of other blood-coagulation factors. Sparsomycin was not toxic to the bone marrow.
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PMID:Pharmacokinetics and toxicology of sparsomycin in beagle dogs. 366 30

We attempted to examine procoagulant activity (PCA), X activator activity (XAA) and plasminogen activator activity (PlgAA) of various leukemic cell lysates: 17 acute myelocytic leukemias (AML), 4 acute promyelocytic leukemias (APL), 9 acute myelomonocytic leukemias (AMMoL), 7 chronic myelocytic leukemias (CML), 4 CML with blastic crisis, 7 T cell acute lymphocytic leukemias (ALL), 8 adult T cell leukemias (ATL), 8 null cell ALL, 6 B cell lymphocytic leukemias. Among those 70 cases, 4 APL, 4 AMMoL and 5 AML were associated with overt disseminated intravascular coagulation (DIC) and 5 T cell ALL, 7 ATL and 2 null cell ALL were associated with hypofibrinogenemia not adapted for DIC. The sample used was the lysate of 10(7) cells. PCA was measured by recalcification time of normal plasma with the cell lysate, XAA and PlgAA was measured by chromogenic substrate. APL and AML, especially those associated with overt DIC, had high PCA, and lymphocytic leukemia generally had low PCA in comparison with normal controls. Total PCA (PCA multiplied by cell count/microliter) was remarkably increased in DIC and mildly increased in ALL with hypofibrinogenemia. The change in XAA and total XAA (XAA multiplied by cell count/microliter) was not remarkable in any leukemia except for T cell ALL and null cell ALL with hypofibrinogenemia. PlgAA was high in lymphocytic leukemias with hypofibrinogenemia, APL and AMMoL with DIC. Total PlgAA (PlgAA multiplied by cell count/microliter) was high especially in T cell ALL and null cell ALL with hypofibrinogenemia. Thus it is probable that PCA is the most important factor causing DIC in myelogenous leukemia and that PlgAA is the most important factor causing hypofibrinogenemia in lymphocytic leukemia. The measurement of these activities in the leukemic cells is valuable in prediction and prevention of the hemostatic disorder in leukemia.
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PMID:Coagulant and fibrinolytic activities in the leukemic cell lysates. 635 39

Complete hemograms were evaluated for 57 rats with mononuclear cell leukemia and compared to hemograms obtained from 52 age- and sex-matched nonleukemic rats. All leukemic rats had marked hemolytic anemia and associated spherocytosis, reticulocytosis, anisocytosis, and polychromasia. The anemia varied with the stage of illness and was more severe in rts with advanced leukemia. Death appeared to be related to anemia. There was a marked neutrophilia with left shift, mild lymphopenia, and moderate to severe thrombocytopenia. Atypical mononuclear cells were detected in circulation in all but three rats. Total white blood cell counts ranged from 5.0-370 x 10(3) cells/ml. There was an increase in erythrocyte osmotic fragility with separation into two distinct populations of erythrocytes. Eight of nine rats were Coombs' positive indicating an immune-mediated pathogenesis for the anemia. Hemostasis tests revealed a markedly prolonged prothrombin time, hypofibrinogenemia, slightly increased to normal partial thromboplastin time, and undetected fibrin degradation products. These findings suggest significant liver disease associated with the leukemia.
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PMID:Pathology of the mononuclear cell leukemia of Fischer rats. II. Hematology. 664 39

All-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL) represents the leading example of targetted drugs for inducing an in vivo differentiation of malignancy (1,2). A fixed dose of 45 mg/m2/day was proposed for the treatment of patients (3), according to the results obtained by retinoic acid derivatives in skin diseases. We report that 25 mg (4), and even 15 mg/m2/day are still effective dosages. Absence of drug resistance, rapid correction of fibrinogenopenia and the absence of hypoplasia are the apparent major advantages and consequently high frequency of early mortality generally reported during chemotherapy is expected to be reduced. In fact the same risk of early death (10%) is recorded in all available data (5), due to coagulation disorders and to a leukocyte activation syndrome. Management of these side-effects is based on the prevention and treatment of the irreversible state as soon as first symptoms appear. Actually the major advantage of ATRA treatment in addition to chemotherapy is the decrease of relapse rate (6), the increase of event-free survival, and thus the increase of survival.
Leukemia 1994
PMID:Induction treatment of acute promyelocytic leukemia using all-trans retinoic acid. Controversies about dosage, advantages and side-effect management. 780 30

The bleeding diathesis in patients with acute promyelocytic leukemia (APL) is generally attributed to disseminated intravascular coagulation (DIC), initiated by the release of procoagulant activity from leukemic cells. Primary fibrinogenolysis, mediated by the release of leukocyte proteases, may also contribute to this disorder. We analyzed coagulation parameters in 15 non-septic APL patients. Before treatment, there was evidence of thrombin activation with DIC: increased levels of circulating thrombin-antithrombin III complexes, prothrombin fragments 1 + 2 and D-Dimer complexes. This DIC syndrome was probably limited, since no prothrombin time decrease, no significant factor V consumption, and normal levels of coagulation inhibitors (antithrombin III and protein C) were observed in APL patients when compared to normal controls. In this context, marked hypofibrinogenemia suggested primary fibrinogenolysis as the predominant etiology. Despite normal or high tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) antigen levels, the plasma PAI-1 activity and the formation of tPA/PAI-1 complexes were lower in APL patients than in normal controls, suggesting a proteolytic degradation of PAI-1, not able to complex tPA. Two other fibrinolytic inhibitor molecules (alpha-2 plasmin inhibitor antigen and histidine-rich glycoprotein antigen) were also significantly reduced, as well as the two subunits of fibrin stability factor XIII, although only subunit A is known to be susceptible to thrombin action. Evidence of degraded forms of von Willebrand factor in the plasma suggested an extended proteolytic activity. Four patients treated with all-trans-retinoic acid (ATRA) as a single differentiating agent were studied serially. A dissociation between these two syndromes--DIC and fibrinogenolysis/proteolysis--was observed. The rapid correction of the lysis markers contrasted with a more prolonged persistence of the procoagulant activity. We observed persistently high elastase/alpha 1-proteinase inhibitor complex levels during ATRA therapy, despite progressive correction of all lysis markers. Thus, the release of elastase from promyelocytic leukemic cells is probably not the only determinant of the fibrinogenolytic/proteolytic syndrome. In summary, the present findings provide new arguments for the association of DIC and proteolysis syndromes in APL-associated coagulation disorders. Further prospective studies are needed in order to confirm the persistence of thrombin activation in course of ATRA therapy.
Leukemia 1993 Jan
PMID:Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment. 841 75

The aims of this study were to analyze the characteristics and outcome of patients with secondary acute promyelocytic leukemia (APL) and compare them to those with primary APL. One hundred and thirteen patients referred to our service with a diagnosis of APL were reviewed. Fourteen were classified as secondary APL. Nine were induced with chemotherapy, and five with all-trans retinoic acid plus chemotherapy. Pretreatment characteristics, response to therapy and outcome of primary vs secondary APL were compared by standard statistical methods. Secondary APL constituted 12% of all APL cases. Patients with secondary APL were significantly older (median age 56 vs 36 years; P < 0.01) and had a lower incidence of hypofibrinogenemia (P < 0.01) than those with primary APL. The complete response (CR) rates were similar with secondary vs primary APL (CR rates 79 vs 69%), as were CR duration and survival. The CR rates at 5 years were 57 and 45%, respectively(P not significant), and the survival rates 37 and 35%, respectively (P not significant). The incidence of secondary APL within APL disease (12%) was similar to the incidence of secondary acute myeloid leukemia (AML) in karyotypes not known to be therapy-related (diploid, t(8;21), inversion 16: incidences 9 to 12%), but was significantly lower than in karyotypes known to be therapy-related (chromosome 5 or 7 abnormalities, 11q; incidences 30 and 33%). We conclude that secondary APL has general characteristics and outcome similar to primary APL. it is more likely a second primary rather than therapy-related AML, and should be treated in a manner similar to primary APL.
Leukemia 1996 Jan
PMID:Secondary acute promyelocytic leukemia. Characteristics and prognosis of 14 patients from a single institution. 855 33


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