Hematologic malignancies and thrombosis.

Patients with hematologic malignancies have an increased risk of venous thromboembolism (VTE), particularly at diagnosis and during the treatment with chemotherapy, asparaginase or immunomodulatory drugs (IMiDs). A disease-dependent hypercoagulable condition associated with other risk factors like drugs, central venous catheter (CVC), immobility and infections are responsible for this high VTE rate. Thrombotic complications have a significant impact on morbidity and in some cases also on mortality of patients with onco-hematologic diseases, therefore thromboprophylaxis to prevent VTE in this setting is needed. However, thrombocytopenia and hemorrhagic complications pone many difficulties in the management of an anticoagulant or antiaggregant treatment in these patients. Recommendations from current guidelines are limited to multiple myeloma patients treated with thalidomide or lenalidomide associated with dexamethasone or chemotherapy, but hematological clinical departments should implement a policy for prevention and treatment of thromboembolic complications in hematologic malignancies.

Bleeding complications of antiangiogenic therapy: pathogenetic mechanisms and clinical impact.

Tumor vasculature and tumor-associated neo-angiogenesis have recently become major targets of antineoplastic therapy. Beside the agents which have already obtained US Food and Drug Administration (FDA) approval for clinical use (thalidomide, lenalidomide, bevacizumab, sunitinib, sorafenib), many others are being tested in clinical trials. Angiogenesis inhibitors, in particular inhibitors of the vascular endothelial growth factor (VEGF) pathway, have shown significant vascular complications, including both thromboembolic and bleeding events. The definition of the clinical impact of bleeding complications (increase in the rate of hemorrhages in comparison with the control group) and the knowledge of the pathogenesis of this toxicity are very important in order to evaluate the results of many studies using antiangiogenic agents in the treatment of cancer patients.

Ifosfamide in hematological malignancies of adults.

Ifosfamide is an alkylating agent with a broad spectrum of activity in solid tumors and hematological malignancies. In this review we will illustrate its use in the treatment of lymphomas and Hodgkin's disease and the results of the principal studies which have investigated ifosfamide-containing regimens. Ifosfamide has been mainly used, in combination with other drugs, as a component of salvage regimens for relapsed or primarily refractory lymphoma. These regimens induced a variable clinical response rate (complete remissions ranging from 6 up to 73% and overall response rate from 24 to 72%). High-dose ifosfamide, in combination with etoposide or mitoxantrone, showed a good potential for mobilization of peripheral stem cells while reducing the tumor burden. Ifosfamide-based regimens are also being evaluated in the treatment of newly diagnosed patients in sequential, response-based protocols, using many non-cross-resistant drugs.