Blood reviews
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For many years, the oral combination melphalan-prednisone (MP) has been considered the standard of care for patients with multiple myeloma (MM) not eligible for autologous stem cell transplantation. In the era of novel agents, the introduction of immunomodulatory drugs and proteasome inhibitors has challenged the role of MP and led to new standards of care for this disease. Five randomized phase III studies compared the traditional MP with the MP plus thalidomide (MPT). ⋯ The availability of different efficacious regimens provided clinicians with the opportunity of tailoring the proper and specific approach for each patient. The choice should be based on patients' comorbidities and biologic age, while taking into account the expected toxicity profiles of each treatment regimen. Moreover, an accurate management of therapy-related adverse events and a gentler approach, particularly for patients older than 75 years, with appropriate age-adjusted dose reductions, should be considered to further improve outcome.
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New effective strategies are required that specifically address the challenges of multiple myeloma (MM) treatment, namely, disease recurrence, immunosuppression, and treatment-related toxicities. Recent preclinical and clinical findings suggest that the IMiDs® immunomodulatory compound lenalidomide has a dual mechanism of action, involving both a direct tumoricidal activity and immunomodulation, which may result in rapid and sustained control of MM, respectively. The tumoricidal effect of lenalidomide occurs through several mechanisms, including disruption of stromal support, induction of tumor suppressor genes, and activation of caspases. ⋯ Lenalidomide in combination with dexamethasone synergistically inhibits proliferation and induces apoptosis; however, dexamethasone appears to antagonize the immune-enhancing effect of lenalidomide. A study has demonstrated that a regimen of lenalidomide in combination with an optimal dose and schedule of dexamethasone may increase survival by allowing synergistic antiproliferative effects, without affecting immunomodulatory activity. As preclinical and clinical research continue, additional insights into the dual mechanism of action of lenalidomide will help to further optimize the use of lenalidomide in MM.
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The survival prospects of critically ill patients with haematological malignancy (HM) are reviewed, as are the variables which might influence decisions about the limitation of life sustaining therapies (LLST). Approximately 40% of patients with HM admitted to ICU survive to hospital discharge and a broad admission policy is warranted. Short term survival is predicted by the severity of the underlying physiological disturbance rather than cancer specific characteristics, although the prognostic importance of neutropenia and prior stem cell transplantation remains to be clarified. ⋯ Patients should be provided with realistic information in order to make an informed decision about CPR. Decisions about LLST must be individualised. Consideration should be given to the patient's wishes and prognosis, the immediate clinical circumstances and their potential reversibility.
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The transfusion approach to massive hemorrhage has continually evolved since it began in the early 1900s. It started with fresh whole blood and currently consists of virtually exclusive use of component and crystalloid therapy. Recent US military experience has reinvigorated the debate on what the most optimal transfusion strategy is for patients with traumatic hemorrhagic shock. ⋯ Lastly we discuss the importance of an established massive transfusion protocol to rapidly employ DCR and hemostatic resuscitation principles. While the majority of recent trauma transfusion papers are supportive of these general concepts, there is no Level 1 or 2 data available. Taken together, the preponderance of data suggests that these concepts may significantly decrease mortality in massively transfused trauma patients.
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As activation of the coagulation pathway is a physiological response to injury, the development of disseminated intravascular coagulation (DIC) is a warning signal to the clinician that the primary pathological disease state is decompensating. In pregnancy, DIC can occur in several settings, which include emergencies such as placental abruption and amniotic fluid embolism as well as complications such as pre-eclampsia. Whilst the acuteness of the event and the proportionality in the coagulant and fibrinolytic responses may vary between these different conditions, a common theme for pregnancy-associated DIC is the pivotal role played by the placenta. ⋯ This is necessary because DIC itself can have pathological consequences that translate clinically into a worse prognosis for affected patients. This article will describe how pregnancy-associated DIC can be diagnosed promptly and how treatment should be managed strategically. It also discusses the latest developments in our understanding of haemostatic mechanisms within the placenta and how these may have relevance to new diagnostic approaches as well as novel therapeutic modalities.