Entries Tagged as 'Semin Hematol'
Advances in antibacterial therapy against emerging bacterial pathogens.
Semin Hematol. 2009 Jul;46(3):198-211
Authors: Pournaras S, Iosifidis E, Roilides E
During the last decade, both gram-positive and gram-negative bacteria that are resistant to most or all available antibacterial classes have become increasingly prevalent nosocomial pathogens, particularly among immunocompromised patients and those hospitalized in intensive care units. Among gram-positive bacteria, increasing concerns are posed for health care- and community-associated methicillin-resistant Staphylococcus aureus (MRSA), S aureus with reduced susceptibility to vancomycin, and vancomycin-resistant enterococci (VRE). A spectrum of newer antibacterial agents has been developed for the treatment of multi-resistant gram-positive bacteria, such as linezolid, tigecycline, daptomycin, and novel glycopeptides. Gram-negative bacteria have also developed multidrug resistance (MDR), which in the Enterobacteriacae is commonly due to the production of extended-spectrum beta-lactamases and carbapenemases of VIM, IMP, or KPC types. Currently, non-fermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii are commonly resistant to all available antibiotics, including the newer agents. Colistin retains activity against most P aeruginosa and A baumannii, but its clinical use remains questionable, while newer carbapenems and tigecycline have limited additional advantages. Rational use of newer antibacterial agents coupled with enhanced infection control measures may be able to sufficiently control MDR organisms as to allow hematological patients to recover from serious infectious complications.
PMID: 19549574 [PubMed - indexed for MEDLINE]
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Neutropenic fever syndromes in patients undergoing cytotoxic therapy for acute leukemia and myelodysplastic syndromes.
Semin Hematol. 2009 Jul;46(3):259-68
Authors: Bow EJ
Fever represents the major surrogate of infection in neutropenic cancer patients. A number of neutropenic fever syndromes have been recognized, the causes and significance of which will vary depending upon the clinical context. First neutropenic fever syndromes are typically of bacterial origin, the character of which may be influenced by whether antibacterial chemoprophylaxis has been administered. Persistent neutropenic fevers are documented during the empirical systemic antibacterial therapy for the first neutropenic fever, the cause of which is likely outside the spectrum of activity of the initial therapy. Recrudescent neutropenic fevers, defined by the appearance of a new fever after defervescence of the first fever, are often a function of invasive fungal infection or gram-positive infections outside the spectrum of the initial empirical antibacterial regimen. The myeloid reconstitution syndrome occurs in parallel with neutrophil recovery from aplasia and may not necessarily represent new infection. Recognition of these patterns can help the clinician make better clinical judgments and management plans.
PMID: 19549578 [PubMed - indexed for MEDLINE]
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Thrombocytopenia in myelodysplastic syndromes and myelofibrosis.
Semin Hematol. 2009 Jan;46(1 Suppl 2):S37-43
Authors: Boruchov AM
Myelodysplastic syndromes (MDS) are a group of hematopoietic stem cell disorders characterized by ineffective hematopoeisis and an increased risk of transforming to acute myelogenous leukemia (AML). Determining the molecular basis of the disease has been hampered by its heterogeneity. Thrombocytopenia is often a manifestation of MDS and needs to be monitored and treated accordingly. Treating the underlying disorder with a variety of differentiation and immunosuppressive agents alleviates the problem in a small percentage of patients but more often complicates the issue. Several treatments used for primary immune thrombocytopenic purpura (ITP) have been tried in MDS patients, though with only modest success rates. Preliminary studies suggest that the use of a thrombopoietic growth factor may afford substantial increases in platelet levels without excessive deleterious side effects. Primary myelofibrosis (MF) is a chronic myeloproliferative disorder associated with hepatosplenomegaly and refractory cytopenias. Immunomodulatory agents have shown promise in treating the anemia associated with this MF. However, there are currently no standard therapies to treat the thrombocytopenia that is often found in patients with this disease.
PMID: 19245933 [PubMed - indexed for MEDLINE]
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Management of chemotherapy-induced thrombocytopenia: current status of thrombopoietic agents.
Semin Hematol. 2009 Jan;46(1 Suppl 2):S26-32
Authors: Vadhan-Raj S
Myelosuppression, one of the most common toxicities of chemotherapy, results in varying degree of cytopenias. While neutropenia and anemia have been reduced with the currently approved hematopoietic growth factors, thrombocytopenia remains a significant clinical problem with an unmet medical need. Although platelet transfusions can provide a temporary solution, they do not address the underlying cause of thrombocytopenia. Management of chemotherapy-associated thrombocytopenia often involves dose reductions or treatment delays. Thrombocytopenia can also affect quality of life and significantly increase healthcare costs. With the introduction of several novel antineoplastic agents with an increased propensity to cause thrombocytopenia, a further increase in the incidence of thrombocytopenia can be expected. Despite the extensive efforts in the clinical development of thrombopoietic agents in the past decade, recombinant interleukin-11 (IL-11) is the only agent currently approved by the US Food and Drug Administration for thrombocytopenia induced by chemotherapy. The use of this agent is limited due to its narrow therapeutic index. While promising biologic activity was observed with recombinant thrombopoietins (TPOs) in nonmyeloablative clinical settings, further clinical development was halted due to evidence of neutralizing antibodies to pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Recently, a number of novel TPO receptor agonists have been developed with promising clinical activity and a lesser potential for immunogenicity. Several of these second-generation platelet-stimulating agents are currently in clinical development, including peptide (romiplostim, formerly AMG-531) and nonpeptide (eltrombopag and AKR501) mimetics. The clinical trials of romiplostim and eltrombopag are currently ongoing to optimize their dose and schedule in ameliorating chemotherapy-induced thrombocytopenia.
PMID: 19245931 [PubMed - indexed for MEDLINE]
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Pathobiology of secondary immune thrombocytopenia.
Semin Hematol. 2009 Jan;46(1 Suppl 2):S2-14
Authors: Cines DB, Liebman H, Stasi R
Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes of secondary ITP differ from each other and from primary ITP, so accurate diagnosis is essential. Immune thrombocytopenia can be secondary to medications or to a concurrent disease, such as an autoimmune condition (eg, systemic lupus erythematosus [SLE], antiphospholipid antibody syndrome [APS], immune thyroid disease, or Evans syndrome), a lymphoproliferative disease (eg, chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia), or chronic infection, eg, with Helicobacter pylori, human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Response to infection may generate antibodies that cross-react with platelet antigens (HIV, H pylori) or immune complexes that bind to platelet Fcgamma receptors (HCV), and platelet production may be impaired by infection of megakaryocyte (MK) bone marrow-dependent progenitor cells (HCV and HIV), decreased production of thrombopoietin (TPO), and splenic sequestration of platelets secondary to portal hypertension (HCV). Sudden and severe onset of thrombocytopenia has been observed in children after vaccination for measles, mumps, and rubella or natural viral infections, including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management.
PMID: 19245930 [PubMed - indexed for MEDLINE]
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