Cancer and its treatments are well-recognized risk factors for venous thromboembolism (VTE). Evidence suggests that the absolute risk depends on the tumor type, the stage or extent of the cancer, and treatment with antineoplastic agents. Furthermore, age, surgery, immobilization, and other comorbid features will also influence the overall likelihood of thrombotic complications, as they do in patients without cancer. The role of hereditary thrombophilia in patients with cancer and thrombosis is still unclear, and screening for this condition in cancer patients is not indicated. The most common malignancies associated with thrombosis are those of the breast, colon, and lung, reflecting the prevalence of these malignancies in the general population. When adjusted for disease prevalence, the cancers most strongly associated with thrombotic complications are those of the pancreas, ovary, and brain. Idiopathic thrombosis can be the first manifestation of an occult malignancy. However, intensive screening for cancer in patients with VTE often does not improve survival and is not generally warranted. Independently of the timing of cancer diagnosis (before or after the VTE), the life expectancy of cancer patients with VTE is relatively short, because of both deaths from recurrent VTE and the cancer itself. Patients with cancer and acute VTE who take anticoagulants for an extended period are at increased risk of recurrent VTE and bleeding. A recent randomized trial, the Randomized Comparison of Low Molecular Weight Heparin versus Oral Anticoagulant Therapy for Long-Term Anticoagulation in Cancer Patients with Venous Thromboembolism (CLOT) study, showed that low molecular weight heparin may be a better treatment option for this group of patients. The antineoplastic effects of anticoagulants are being actively investigated with promising preliminary results.

Venous Thromboembolism and Cancer: Risks and Outcomes

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.

Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention.

Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children's Leukemia Group phase 3 trial.

Chemotherapy-induced thrombosis.

Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients

A syndrome of thrombosis and hemorrhage complicating L-asparaginase therapy for childhood acute lymphoblastic leukemia.

Intracranial hemorrhage and focal seizures secondary to use of l-asparaginase during induction therapy of acute lymphocytic leukemia

The use of antithymocyte globulin in the treatment of severe aplastic anemia in children

Tumor Lysis Syndrome

The benefit of antithymocyte globulin in severe aplastic anemia in the pediatric age group was assessed Four children received ten alternate-day courses of A TG (horse antihuman thymocyte globulin) as well as antihistamines and corticosteroids to minimize allergic reactions. The outcome of 19 other children with severe aplastic anemia who received A TG was also summarized. Combined data reveal that 12 of 23 have had a complete or partial response with residual thrombocytopenia and a probability of 48% survival one year from the start of A TG therapy as projected by life table analysis. Only one death has been recorded in the responding group. Response rate did not appear to be influenced by age, sex, etiology, initial blood count, interval prior to A TG therapy, or dose of A TG employed. Complications were minimal and included minor urticarial reactions and intermittent fever. Therapy with A TG should be considered in childhood severe aplastic anemia when bone marrow transplantation is not possible.

Mitchell S. Cairo

Papers

A syndrome of thrombosis and hemorrhage complicating L-asparaginase therapy for childhood acute lymphoblastic leukemia.

Intracranial hemorrhage and focal seizures secondary to use of l-asparaginase during induction therapy of acute lymphocytic leukemia

The use of antithymocyte globulin in the treatment of severe aplastic anemia in children

Tumor Lysis Syndrome

The use of antithymocyte globulin in of severe aplastic anemia in children the treatment