Seminars in hematology
-
Seminars in hematology · Apr 2008
ReviewSafety update on recombinant factor VIIa in the treatment of congenital and acquired hemophilia.
Recombinant activated factor VII (rFVIIa) appears to be safe when used for its licensed indication of congenital and acquired hemophilia A or B with inhibitors. One should carefully consider the clinical indication for which the agent is used when patient risk factors are present that might predispose the subject to a thromboembolic (TE) event, or when concomitant hemostatic agents are being used. ⋯ However, the incidence of serious TE events in hemophilia patients with inhibitors treated with rFVIIa appears to be much less than 1%. The role of rFVIIa in off-label indications should be assessed through rigorously controlled clinical trials or by analyzing carefully collected data from national and international registries.
-
Seminars in hematology · Jul 2007
ReviewRisks and benefits of erythropoiesis-stimulating agents in cancer management.
Anemia is frequently diagnosed in patients with cancer and its treatment is an important clinical problem. The deficiency in red blood cells (RBCs) can be a debilitating problem, and anemia correlates with poor performance status, deteriorates quality of life, and may negatively influence the prognosis of cancer patients. The development of recombinant human erythropoietins (rhEPO) provides a therapeutic option in patients with mild to moderate anemia. ⋯ The dosing and management of these patients should strictly follow evidence-based guidelines of the clinical societies, as well as the manufacturer's recommendations. Furthermore, treatment of patients beyond the correction of anemia must be regarded as potentially harmful and should only be conducted in an experimental clinical setting. In this review, recently published recommendations and standards for the use of rhEPO will be discussed.
-
Seminars in hematology · Jan 2007
ReviewResistance to targeted therapy in chronic myelogenous leukemia.
The advent of the Bcr-Abl selective tyrosine kinase inhibitor imatinib mesylate (Glivec, Gleevec, Novartis, East Hanover, NJ) has substantially changed the treatment landscape for chronic myelogenous leukemia (CML). However, some patients, primarily those with advanced disease, are either initially refractory to imatinib or eventually develop imatinib resistance. Imatinib resistance or intolerance frequently depends on the re-emergence of Bcr-Abl kinase activity, but can also indicate Bcr-Abl-independent disease progression. ⋯ Early mutation detection may aid in risk stratification and molecular-based treatment decisions. To overcome imatinib-resistant disease, novel tyrosine kinase inhibitors with activity against imatinib-resistant mutations and/or with inhibition of alternative pathways, such as Src activation, have recently been developed. Additional strategies include imatinib dose escalation, combination therapy, and treatment interruption to stop clonal selection of resistant cells.
-
Seminars in hematology · Jan 2007
ReviewNew targeted therapies for chronic myelogenous leukemia: opportunities to overcome imatinib resistance.
The advent of tyrosine kinase inhibitors (TKIs) has ushered in a new era in the management of chronic myelogenous leukemia (CML). Imatinib, the first TKI to be approved for the treatment of CML and the current standard first-line therapy, has significantly improved the prognosis of patients with CML. Nevertheless, a minority of patients in chronic-phase CML and even more patients with advanced-phase disease demonstrate resistance to imatinib or develop resistance during treatment. ⋯ These include: dasatinib, a potent dual Bcr-Abl and Src inhibitor; nilotinib, a selective, potent Bcr-Abl inhibitor; bosutinib (SKI-606) and INNO-406 (NS-187), which are both Src-Abl inhibitors; and others. Combination therapy is also being explored concurrently using agents that affect a variety of oncogenic pathways and immune modulation. Herein, we review some of these strategies, particularly those for which clinical data are currently available.