Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with acute leukemia undergoing remission induction chemotherapy occasionally develop venous thrombosis despite severe thrombocytopenia and in the absence of disseminated intravascular coagulation. This observation prompted us to study the levels of the naturally occurring anticoagulant proteins C and S prospectively in patients undergoing remission induction chemotherapy for acute leukemia. Plasma samples from 50 adult patients with acute leukemia (34 AML, 16 ALL) were analyzed for protein C antigen, functional protein C, immunologic total and free protein S as well as levels of C4b binding protein (C4bBP). Plasma levels of immunologic protein C were significantly lower in patients with active acute myelocytic leukemia (mean = 77.9) than in controls (mean = 123.6) or patients in remission (mean = 132). Functional protein C levels were also significantly lower in AML patients with active disease (mean = 58.5) than controls (mean = 95.5) or patients in remission (mean = 98.5). Patients with acute lymphocytic leukemia (ALL) had normal levels of immunologic and functional protein C. Although total protein S levels were normal in all patients studied, levels of free protein S were significantly decreased in patients with active AML (mean = 29.3) compared with patients in remission (mean = 42.0) or controls (mean = 42.4). In contrast, patients with ALL, both with active disease and in remission had normal free protein S levels. This decrease in free protein S seen in active AML was not associated with liver disease, white cell count or an increase in C4bBP. These findings provide a possible explanation for the occasional occurrence of venous thrombosis in patients with acute myelocytic leukemia.
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PMID:Protein C and S levels in acute leukemia. 183 Apr 52

Eight pts with acute myeloid leukemia were studied to assess coagulation and fibrinolysis disturbances as a cause of hemorrhages associated to thrombopenia. Fibrinogen, products of fibrinogen to fibrin degradation, D-dimer, antithrombin III, protein C, plasminogen and alpha-2 antiplasmin determinations were performed at admission, during and after chemotherapy. All pts were on heparin during induction chemotherapy. Coagulation activation, which increased with the onset of chemotherapy (increases in D-dimer) and a decreasing trend at the end of the antileukemic therapy (normalization of fibrinogen levels) was observed. During the whole observation period alpha-2 antiplasmin levels remained very low. No significant changes were observed in antithrombin III or protein C levels. In conclusion, disseminated intravascular coagulation with associated thrombopenia is an important event in acute leukemia and an increased fibrinolytic activity due to low alpha-2 antiplasmin levels may take part in the genesis of hemorrhage. These data suggest that both heparin administration and the use of antifibrinolytic drugs may have a therapeutic effect.
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PMID:[Intravascular coagulation in acute promyelocytic leukemia: analysis of coagulation and fibrinolysis parameters]. 184 6

An efficiency of the acute myeloblastic leukemia therapy has been assessed in 79 patients aged over 60 years. Twenty six patients out of this group have been treated with usual or reduced doses of doxorubicin and cytarabine (ADR-Ara-C) 35--low doses of cytarabine (LD Ara-C), 11-6-mercaptopurine (6 MP), and 7 patients died before chemotherapy. Complete remission in group treated with ADR-Ara-C was achieved in 23% of patients while partial remission in 42%. Median survival in this group was 5.8 months (range from 0.5 to 16 months). Percentage of the complete remissions in the group treated with LD-Ara-C was 6%, and partial remissions 40%. Median survival was 4.7 months (range from 0.5 to 14.2 months). Partial remission in 5 out of 11 patients treated with 6 MP (36%) and no complete remissions were noted. Median survival was 3.9 months. Therapy with ADR-Ara-C produced marked leucopenia and thrombocytopenia in the majority of treated patients. Vomiting, hemorrhagic complications, and bacterial infections have also been noted. These adverse reactions have been less frequent in patients treated with LD-Ara-C, and 6 MP. Ten patients (38%) treated with ADR-Ara-C and 7 patients treated with LD-Ara-C died during remission inducing therapy.
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PMID:[Results of treating acute myeloblastic leukemia in patients over 60 years of age]. 184 11

Among 35 patients with relapsed or refractory acute myelogenous leukemia (AML) who received salvage chemotherapy, 28 were treated with mitoxantrone (7.5 mg/m2/d intravenously [IV] over 1 hour for 5 days) and etoposide (VP-16) (2 g/m2 over 4 days either as a daily infusion or as two daily doses). Seven patients received mitoxantrone (6 mg/m2/d for 5 days) and VP-16 (1500 mg/m2 over 3 days). The median duration of the initial complete remission (CR) was 6 months and 83% of the patients had initial CR that lasted 12 months or less. Forty-six percent of the patients were undergoing a second or subsequent salvage attempt. Eight patients (23%) achieved CR; seven of these CR were obtained after one course of therapy. Twelve patients (33%) died and 15 patients (42%) had disease that was resistant to treatment. Patients undergoing a first salvage attempt had a higher incidence rate of CR than those undergoing a second or subsequent salvage attempt (37% versus 6%; P = 0.03). CR rates were also higher in patients with a favorable (translocation 8;21 or 15;17) or diploid karyotype compared with other patients (32% versus 8%; P = 0.10). The median survival time was 2 months for all patients and 8 months for patients achieving CR. Mucositis occurred in 74% of the patients and was severe in 32%. Diarrhea and rash occurred in less than 33% of the patients. Fever was noticed in all but 1 of the patients and documented infections occurred in 65% of the patients. Six patients had pancytopenia or thrombocytopenia that lasted more than 42 days from the initiation of treatment. Although mitoxantrone and high-dose VP-16 is an effective antileukemic regimen, it is associated with a high incidence of mucositis. Strategies that are used to limit mucosal damage may improve the tolerance of this combination.
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PMID:Mitoxantrone and high-dose etoposide for patients with relapsed or refractory acute leukemia. 185 68

The authors describe the clinical history of two adult patients with acute myeloid leukemia, who had severe neutropenia and thrombocytopenia. After chemotherapy in both patients had developed typhlitis with fatal outcome caused by sepsis. They discuss the etiopathogenesis and clinical features of necrotizing typhlitis as a complication of treated acute leukemia and point out the difficulty of the differential diagnosis and management.
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PMID:[Typhlitis as a complication of acute leukemia]. 186 61

Twenty-two patients with acute myeloid leukemia (AML), having a median age of 48.3 years (range 26-70; 10 male, 12 female), were treated with 4'-(9-acridinylamino) methanesulphon-m-anisidide (m-AMSA) 100 mg/m2 and cytosine arabinoside (AraC) 2 x 1000 mg/m2i.v. on days 1-5. There were 2M1,8 M2, 9 M4, 2M4 Eo, and 1 M5a. Of these, 12 achieved a complete remission, 3 a partial remission and 6 did not respond. The median remission duration was 9.0 months and the median overall survival 8.1 months. Side-effects of induction consisted mainly of haematological toxicity and infections with a median duration of WHO-grade-4 granulopenia and thrombopenia of 20 and 28 days respectively. Organ toxicity was mild with mucositis and cutaneous and liver toxicity being experienced by only a few patients. There was one treatment-related death. Five-day m-AMSA and intermediate-dose AraC is an easy-to-handle condensed treatment schedule with tolerable toxicity. Its effectiveness in relapsed and refractory AML is comparable to combinations of high-dose AraC with m-AMSA, anthracyclines or etoposide.
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PMID:Five-day 4'-(9-acridinylamino)methanesulphon-m-anisidide and intermediate-dose cytosine arabinoside in high-risk relapsing or refractory acute myeloid leukemia. 189 Jan 42

A total of 32 patients (15 men and 17 women) presenting with relapsing or refractory acute leukemia were treated with a 3-h infusion of 3 g/m2 cytosine arabinoside (ara-C) twice daily on days 1-6 and a 1-h infusion of 100 mg/m2 etoposide on days 1-5. In all, 6 subjects had acute lymphocytic leukemia (ALL); 25 had acute myeloid leukemia (AML) of types M1 (n = 6), M2 (n = 10), M4 (n = 5), and M5 (n = 4); and 1 had mixed-type leukemia. The median age was 35 years (ranges, 16-62 years). Of the patients presenting with AML, 11 were primarily refractory and 3 became refractory after their first relapse. Six subjects had an early first relapse following a complete remission (CR) that lasted less than 6 months and five, a second relapse. Another patient underwent a primary relapse after greater than 6 months but had been heavily pretreated. In all, 5 subjects with refractory AML achieved a CR (36%; 95% confidence interval (CI), 10%-62%) as did 7 patients exhibiting relapsing AML (58%; CI, 30%-86%). Three patients who had relapsing or resistant ALL achieved a CR. Side effects consisted of severe hematotoxicity associated with granulocytopenia of less than 500/mm3 that lasted for a mean of 23.6 days and thrombocytopenia of less than 20,000/mm3 whose mean duration was 20.8 days. Marked gastrointestinal toxicity and infections were also prevalent. Cutaneous and ocular toxicity as well as allergic, pulmonary and cerebellar side effects were observed in a few cases. We conclude that the combination of high-dose ara-C and etoposide is a powerful but toxic induction regimen for refractory or relapsed acute leukemia.
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PMID:High-dose ara-C and etoposide in refractory or relapsing acute leukemia. 193 54

Bleeding and septicemia are the most common causes of death in patients with acute leukemia. Additionally to thrombopenia, which is present in most patients, in part of the patients severe coagulation abnormalities are observed. The prevalence of severe coagulation abnormalities in patients with acute myeloid leukemia including all FAB types is around 12%, in patients with promyelocytic leukemia the prevalence is more than 50%. The etiology of this coagulation abnormality remains unclear. There are 3 mechanisms currently under discussion: activation of coagulation, activation of fibrinolysis and an increased activity of specific leucocyte proteases. In particular, in promyelocytic leukemia the risk of cerebral bleeding is high (10 to 15% of early deaths). The most important therapeutic consequence is an intensified thrombocyte replacement regimen. Additional therapeutic efforts, like administration of heparin or antifibrinolytic drugs, have failed to improve the prognosis of patients with severe coagulation abnormalities.
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PMID:[Blood coagulation disorders in leukemia]. 194 47

Fourteen patients with acute myeloid leukemia (AML) were autotransplanted with peripheral blood cells collected during early remission. Seven were autotransplanted in first relapse and seven in first remission. They received a median of 3.3 X 10(8) nucleated cells/kg body weight (BW) and 92 X 10(4) myeloid progenitor cell (CFU-GM) per kg BW. Rapid hemopoietic reconstitution (HR) occurred in all patients with median time to reach normal neutrophil and platelet counts 13 and 18 days post re-infusion respectively. However, in three patients neutrophil counts fell to less than 1.0 x 10(9)/l and in seven patients platelet counts fell to less than 25 x 10(9)/l between 26 and 40 days post-transplant (trough count). In all but two patients who received the lowest CFU-GM dose the counts returned to normal or near normal levels (steady count). There were significant correlations between the CFU-GM dose and the trough and the steady platelet counts (p = 0.04 and 0.01 respectively). Patients receiving more than 50 x 10(4) CFU-GM/kg BW had higher steady neutrophil and platelet counts (p = 0.011 and 0.033 respectively) although some patients receiving greater than 50 x 10(4) CFU-GM/kg still experienced thrombocytopenia during the second month post graft. There was no significant correlation between the nucleated cell dose and HR. The cause of the fall in platelet and neutrophil counts in the second month post graft is not clear but is probably a reflection of a proliferative defect in the recovery phase stem cells in AML.
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PMID:An unusual pattern of hemopoietic reconstitution in patients with acute myeloid leukemia transplanted with autologous recovery phase peripheral blood. 197 98

The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels.
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PMID:Fludarabine: a review. 206 37


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