Expert review of hematology
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Effective therapy for multiple myeloma has existed for a little more than the last half century. The introduction of melphalan 55 years ago was followed by a stagnant period of four decades in which many combinations of alkylating agents and chemotherapeutic drugs were developed without a significant increase in overall survival. The first novel agent, thalidomide, was introduced 15 years ago when it was used as an anti-angiogenesis agent. ⋯ Then lenalidomide, a second-generation analog of thalidomide was introduced. More recently carfilzomib, a proteasome inhibitor, and pomalidomide, a third-generation derivative of thalidomide have entered the marketplace. Many new agents are in development and potentially available for future therapy.
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Smoldering or asymptomatic multiple myeloma may be best described as a state of limbo where the patient has not developed any symptoms of disease and is being observed expectantly. With the advent of novel agents in myeloma therapy, several clinical investigations are underway to determine whether early intervention will help improve survival outcomes in this patient population. Mateos MV et al. report on the first Phase III trial in smoldering multiple myeloma that has shown overall survival benefit. The commentary discusses the study design, key results and potential implications of the study.
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The risk of CNS dissemination and CNS prophylaxis strategies in aggressive non-Hodgkin lymphoma (NHL) is still debated. CNS dissemination is a rare but fatal event. ⋯ Risk models in the rituximab era were modulated for the detection of occult CNS disease at diagnosis using flow cytometry. The optimal regimen for CNS prophylaxis in aggressive lymphoma patients has not been established thus far and should be modulated at different levels of 'intensity' such as standard intrathecal chemotherapy, 'active' intrathecal chemotherapy with liposomal cytarabine or more aggressive systemic treatment with high doses of drugs having good CNS bioavailability reserved for patients who are truly at high risk of CNS dissemination.
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Drugs that selectively inhibit Bruton's tyrosine kinase (BTK), such as the new orally administered agent ibrutinib, are currently under investigation for the treatment of several types of B-cell malignancies. In this article, the authors present results of a Phase Ib/II study of ibrutinib in 85 patients with relapsed or refractory chronic lymphocytic leukemia (CLL). ⋯ In addition, the use of an effective oral agent like ibrutinib whose efficacy does not translate into a high burden of toxicity should be considered in choosing therapy in the elderly. A challenging issue with ibrutinib is the possibility of overcoming chemotherapy in the treatment of CLL.
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Fibrinogen plays a key role in the coagulation process, and therefore maintaining adequate quantities of fibrinogen is an essential step in achieving satisfactory hemostasis in patients with acquired hypofibrinogenemia. Potential options for treating acquired hypofibrinogenemia in patients with uncontrolled bleeding include the use of cryoprecipitate or fibrinogen replacement therapy. This review provides a brief overview of the hemostatic process and the methods for assessing coagulopathy and discusses the efficacy and safety of cryoprecipitate and fibrinogen concentrate in restoring fibrinogen levels, achieving hemostasis and reducing transfusion requirements in different patient populations requiring rapid hemostasis. Other issues relevant to the clinical use of these agents in restoring hemostasis, including variations in product composition, preparation time and cost, are also examined.