Best practice & research. Clinical haematology
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For many years the treatment of multiple myeloma was limited to such regimens as melphalan-prednisone, high-dose dexamethasone, and vincristine-doxorubicin-dexamethasone (VAD). These combinations provided response rates of 45-55%, with complete remission rates of up to 10%. ⋯ Lenalidomide, a thalidomide analog, was developed with the hope of improving both the efficacy and toxicity profile of thalidomide, and has subsequently shown significant clinical activity in patients with multiple myeloma. We describe the role of lenalidomide in patients with symptomatic multiple myeloma that is newly diagnosed, relapsed and/or refractory to other therapies, or concurrent with primary amyloidosis.
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Best Pract Res Clin Haematol · Dec 2007
ReviewFrontline treatment in multiple myeloma patients not eligible for stem-cell transplantation.
Melphalan-prednisone-thalidomide (MPT) currently appears to be the treatment of choice for a large proportion of elderly patients ineligible for autologous stem-cell transplantation (ASCT). It seems certain that in the near future melphalan-prednisone-Velcade (MPV) and melphalan-prednisone-lenalidomide (MPR) will also be proved superior to melphalan-prednisone (MP), thus providing three therapeutic options (MPT, MPV and MPR) in this patient group with multiple myeloma (MM). These therapeutic options could lead to more personalized treatment approaches, based on patient comorbidities, as the three novel therapies have somewhat different toxicity profiles. ⋯ Questions regarding the relative efficacy of melphalan-based regimens versus dexamethasone-based regimens (preferably with low-dose dexamethasone) will require randomized phase-III trials. More intensive approaches with new drug combinations or with the incorporation of polyethylene glycolated (PEGylated) liposomal doxorubicin will also require additional studies. Additionally, the important issue of maintenance treatment needs to be further investigated, especially in elderly patients.
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The past two decades have seen a major paradigm shift in the therapy of chronic lymphocytic leukemia (CLL), with the treatment goal shifting from symptom palliation to the attainment of maximal disease control using the most effective frontline regimens available, thus prolonging survival and possibly leading to cure. The most potent therapeutic regimens developed to date include the chemoimmunotherapy combinations incorporating purine analogs and monoclonal antibodies. We review the evolution of modern chemoimmunotherapy for CLL, and discuss current research directions for further refining the potency of these regimens.
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Best Pract Res Clin Haematol · Jan 2006
ReviewPlasma and plasma components in the management of disseminated intravascular coagulation.
A variety of clinical conditions can cause systemic activation of coagulation that ranges from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). DIC consists of a widespread systemic activation of coagulation, resulting in diffuse fibrin deposition in small and midsize vessels. There is compelling evidence from clinical and experimental studies that DIC is involved in the pathogenesis of microvascular dysfunction and contributes to organ failure. ⋯ Recent insight into important pathogenetic mechanisms that might lead to DIC has resulted in novel preventive and therapeutic approaches to patients with sepsis and derangement of coagulation. Supportive strategies aimed at inhibition of coagulation activation might theoretically be justified and have been found beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation or restoration of physiological anticoagulant pathways.
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Best Pract Res Clin Haematol · Jan 2006
ReviewPlasma and plasma products in the treatment of massive haemorrhage.
Massive haemorrhage requires the use of plasma products when it is accompanied by a coagulopathy or when the more than one blood volume has been lost and intractable bleeding continues. The coagulopathy results from haemorrhagic shock, hypothermia, and activation, consumption and dilution of coagulation factors. Plasma products have a critical role in maintaining sufficient levels of coagulation proteins to ensure haemostasis can occur. ⋯ Recombinant factor VIIa has now been shown to have a role in massive haemorrhage. Randomised controlled trials are currently underway to determine the optimal dose and timing of its administration. The physiology and management of the coagulation disturbance using plasma products in the massive haemorrhage of specific clinical situations are described.