Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytostatic antibiotics of the anthracycline class are the best known of the chemotherapeutic agents that cause cardiotoxicity. Alkylating agents such as cyclophosphamide, ifosfamide, cisplatin, carmustine, busulfan, chlormethine and mitomycin have also been associated with cardiotoxicity. Other agents that may induce a cardiac event include paclitaxel, etoposide, teniposide, the vinca alkaloids, fluorouracil, cytarabine, amsacrine, cladribine, asparaginase, tretinoin and pentostatin. Cardiotoxicity is rare with some agents, but may occur in >20% of patients treated with doxorubicin, daunorubicin or fluorouracil. Cardiac events may include mild blood pressure changes, thrombosis, electrocardiographic changes, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, cardiac failure (left ventricular failure) and congestive heart failure. These may occur during or shortly after treatment, within days or weeks after treatment, or may not be apparent until months, and sometimes years, after completion of chemotherapy. A number of risk factors may predispose a patient to cardiotoxicity. These are: cumulative dose (anthracyclines, mitomycin); total dose administered during a day or a course (cyclophosphamide, ifosfamide, carmustine, fluorouracil, cytarabine); rate of administration (anthracyclines, fluorouracil); schedule of administration (anthracyclines); mediastinal radiation; age; female gender; concurrent administration of cardiotoxic agents; prior anthracycline chemotherapy; history of or pre-existing cardiovascular disorders; and electrolyte imbalances such as hypokalaemia and hypomagnesaemia. The potential for cardiotoxicity should be recognised before therapy is initiated. Patients should be screened for risk factors, and an attempt to modify them should be made. Monitoring for cardiac events and their treatment will usually depend on the signs and symptoms anticipated and exhibited. Patients may be asymptomatic, with the only manifestation being electrocardiographic changes. Continuous cardiac monitoring, baseline and regular electrocardiographic and echocardiographic studies, radionuclide angiography and measurement of serum electrolytes and cardiac enzymes may be considered in patients with risk factors or those with a history of cardiotoxicity. Treatment of most cardiac events induced by chemotherapy is symptomatic. Agents that can be used prophylactically are few, although dexrazoxane, a cardioprotective agent specific for anthracycline chemotherapy, has been approved by the US Food and Drug Administration. Cardiotoxicity can be prevented by screening and modifying risk factors, aggressively monitoring for signs and symptoms as chemotherapy is administered, and continuing follow-up after completion of a course or the entire treatment. Prompt measures such as discontinuation or modification of chemotherapy or use of appropriate drug therapy should be initiated on the basis of changes in monitoring parameters before the patient exhibits signs and symptoms of cardiotoxicity.
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PMID:Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. 1078 23

This report describes the long-term (23 years) follow-up of a pediatric patient with acute lymphoblastic leukemia and eosinophilia who underwent multiple valve replacements. An 8-year-old boy with this complex disease was admitted in January 1984 and treated with 6-week course of vincristine, L-asparaginase, and prednisolone, which induced complete remission. He developed atrioventricular valvular insufficiency and infectious endocarditis at 13.5 and 17.3 years of ages, respectively, with progressive development of congestive heart failure. At 18.6 years of age, he underwent prosthetic valve replacement of both atrioventricular valves; the mitral valve was replaced with a mechanical prosthetic valve and tricuspid valve with a bioprosthetic valve. Histopathological examination of the ventricular endomyocardium showed extensive fibrous degeneration and persistent infiltration of eosinophils and lymphocytes. The right-side prosthesis was replaced twice, at 22.4 and 29 years of ages, due to degeneration of bioleaflets and thrombosis of the mechanical valve, respectively. Although he tolerated all surgical procedures, he developed liver cancer at 31 years of age and died. Autopsy could not be performed. The present study indicates that a subset of patients in complete remission of acute lymphoblastic leukemia and eosinophilia can show persistent myocardial eosinophilic infiltration and are at risk of late cardiac disease.
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PMID:Persistent eosinophilic infiltration of the myocardium in a child in complete remission of acute lymphoblastic leukemia and eosinophilia. Potential role in late cardiac disease? 2060 42