Reviews in clinical and experimental hematology最新文献

In spite of recent advances in the treatment of myelodysplastic syndromes (MDS), supportive care remains a very important part of the therapy. Red blood cells transfusions are the most important component of this supportive care. They transiently relieve anemia symptoms and alleviate their effects on quality of life and daily functioning. Platelet transfusion therapy is less frequently needed, at least in low-risk MDS. Dealing with an increased risk of infections linked to neutropenia, mainly by broad spectrum antibiotics, is also needed, more often in advanced stages of [dict: MDS] or when the MDS evolves to acute myeloid leukemia. Chronic red blood cell transfusions expose patients to various side-effects, including blood components intolerance reactions and alloimmunization risks, but also increased frequency of iron overload, a more significant problem in low-risk heavily transfused MDS patients, who have prolonged life expectancy. The use of growth factors is becoming a more and more important part of current supportive care. High-dose erythropoietin is able to reduce or suppress red blood cell transfusions needs in selected subgroups of MDS. The short-term use of granulocyte colony-stimulating factor is also often proposed in infections, although not formally established by prospective trials. Although trials of growth factors with thrombopoeitic activity have been performed with interleukin 11 and are underway with thrombopoeitin, none of them are available for routine use.

A number of clinical, laboratory, morphological and genetic factors are useful to predict the natural course of Myelodysplastic syndromes (MDS). The identification of these factors resulted in the development of scoring systems that aid to differentiate high risk patients from those with a better prognosis. At the initial approach towards a patient with MDS the clinician will take into account the individual's age and performance score, and the morphological characteristics of the peripheral blood and bone marrow, including number of dysplastic lineages and blast count, as proposed by the new World Health Organization classification. Some laboratory features like the neutrophil and platelet count and the lactate dehydrogenase levels are of additional independent prognostic importance. Finally, the karyotype of the malignant hematopoietic cells is a very strong prognostic variable and therefore mandatory in the assessment of patients with MDS. By using part of the above-mentioned factors, the International Prognostic Scoring System has proven reliable in grouping MDS patients into one of four risk categories and can be used in the stratification of patients in therapeutic trials. With the avenue of more sophisticated molecular techniques like gene expression profiling, it might become possible not only to predict the natural course of the disease more precisely, but also to identify patient populations that are prone to respond to specific drugs especially designed for specific genetic lesions.

Cancer patients are at increased risk for thrombosis. Among the predisposing factors for the hemostatic imbalance, drugs have a definite role. Induction of thrombosis by drugs involves a variety of mechanisms: Enhancement of procoagulant activity, reduction in anticoagulants synthesis, stimulation of platelet aggregation and endothelial damage. L-asparaginase is associated with thrombotic events, mainly in the venous system. Supportive therapy with fresh frozen plasma is probably insufficient and heparin needs further evaluation. Venous thromboembolism has recently emerged following thalidomide use particularly in combination chemotherapy. The hematopoietic growth factors granulocyte colony-stimulating factor, macrophage-granulocyte colony-stimulating factor and erythropoietin have also been implicated in venous as well as in arterial thrombotic events. Numerous drugs are associated with thrombotic microangiopathy i.e., cyclosporine A, tacrolimus, cisplatin, bleomycin, gemcitabine. The clinical presentation, pathological mechanisms and therapeutic modalities are discussed.

Hepatic veno-occlusive disease (VOD) is one of the most important complications following hematopoietic stem cell transplantation (SCT) and is associated with a very high mortality when severe. This review addresses the pathogenesis and clinical features of VOD and outlines the role on endothelial cell injury and risk factors. The current status of research for both treatment and prevention are discussed.

The association between thrombosis, bleeding and neoplastic disease is well recognized. There are distinctive features of the thrombotic and bleeding complications associated with specific hematologic malignancies. A number of procoagulants can initiate intravascular clotting including tissue factor, cancer procoagulant and interleukin-1. The hematologic malignancy most often associated with intravascular clotting and bleeding is acute promyelocytic leukemia. The pathogenesis of the life-threatening bleeding disorder associated with this uncommon subtype of acute myeloid leukemia (AML) is complex and involves disseminated intravascular coagulation, fibrinolysis and proteolysis. Both all-trans retinoic acid and arsenic trioxide result in relatively rapid resolution of the coagulopathy. Intravascular clotting may also be induced by hyperleukocytosis in AML and by the hyperviscosity syndrome observed in multiple myeloma and Waldenström's macroglobulinemia. In the setting of hematologic malignancies, when thromboembolic complications occur, the presence of comorbid thrombophilic conditions should be excluded. Abnormal platelet production and function contribute to the development of thrombosis in patients with myeloproliferative disorders. The Budd-Chiari syndrome may be observed in patients with myeloproliferative disorders. A number of medications have thrombogenic potential, including corticosteroids, thalidomide, L-asparaginase, all-trans retinoic acid and arsenic trioxide.

This review is based on pediatric reports (- January 2004) on the presence of symptomatic thrombosis in children with hematologic malignancies, mainly acute lymphoblastic leukemia, treated with different treatment protocols and associated with acquired and inherited prothrombotic risk factors (factor V G1691A, factor G20210A, MTHFR C677T genotypes, protein C, protein S, antithrombin, elevated levels of lipoprotein(a), and homocysteine). The interactions of treatment modalities, study designs, ethnical backgrounds and associated central lines are discussed. Based on the data presented here, we suggest the use of prednisone and E. coli asparaginase concomitantly administered in a leukemic patient suffering a prothrombotic risk factor to be responsible for the onset of venous thrombosis in the majority of cases. In addition, primary preventive anticoagulant/antithrombotic strategies are discussed.

For many years central venous catheters (CVC) have been utilized to monitor hemodynamics and to deliver parenteral nutrition, blood products, pharmacological therapies or infusion fluids. Recently, CVC use has greatly increased with significant impact on the administration of chemotherapy, stem cell transplantation and other treatments to cancer patients. However, CVC use may be accompanied by a variety of side-effects, which increase with the duration of implantation. The most common catheter-related complications are thrombotic events and blood-stream infections. The true incidence of these complications is still uncertain and has changed over time due to CVC device improvement. More data are available in solid tumor than in oncohematologic patients. Recently, much attention has been paid to the issues of prevention and treatment of these complications. Some strategies have been proposed: fixed dose warfarin or low molecular weight heparins have been evaluated in some clinical trials of thromboprophylaxis in this condition. However, more studies are still needed to address this issue. This review will focus on CVC use and complications in oncohematologic patients.