Current opinion in hematology
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Curr. Opin. Hematol. · Mar 1998
ReviewPotential therapeutic approaches for the treatment of vaso-occlusion in sickle cell disease.
Vaso-occlusion is the major cause of morbidity and mortality in sickle cell disease. The pathogenesis of vaso-occlusion likely involves many complex steps related to both the primary event of deoxyhemoglobin S polymerization and the many resultant pathologic changes in both the sickle erythrocyte and the vascular endothelium. ⋯ Although gene therapy is actively being pursued, the ability to cure sickle cell disease is currently limited to bone marrow transplantation with its attendant toxicities and limitations. Because the pathophysiology of vaso-occlusion in sickle cell disease is complex, its treatment will likely be optimized using a multifactorial therapeutic approach.
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Use of bone marrow transplant therapy has been limited both by the availability of suitable stem cell donors as well as the various immunologic complications, namely graft-versus-host disease (GVHD) and profound immunosuppression resulting in opportunistic infection. As of March 1997, more than 450 patients with various malignant and nonmalignant diseases have been transplanted with umbilical cord blood from related and unrelated donors. Preliminary results suggest that rate of engraftment is high and risk of severe GVHD is low, regardless of donor type. ⋯ The overall survival in recipients of unrelated donor umbilical cord blood grafts is 0.40 +/- 0.12 at 2 years after transplantation. Notably, no risk factor predicted higher risk of GVHD and only cell dose (P = 0.04) and possibly, degree of HLA mismatch (P = 0.06) impacted survival in multiple regression analysis. Although these data verify earlier reports that sufficient numbers of hematopoietic stem cells exist in umbilical cord blood for most recipients and that risks of acute and chronic GVHD are low despite increased HLA disparity, these data also provide us with a statistical analysis indicating which demographic, graft, and treatment factors possibly influence various outcomes after transplantation.
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Sickle cell disease is characterized by recurrent episodes of acute pain. Some patients also suffer from chronic pain syndromes including avascular necrosis, leg ulcers, and intractable pain. Approaches to rational therapy of sickle pain include pharmacologic, nonpharmacologic, and preventive therapeutic interventions. ⋯ Administration of opioids on a fixed schedule or by patient-controlled analgesia is ideal for effective therapy. Nonpharmacologic approaches to manage sickle pain are underutilized and more studies are needed to determine their role in sickle pain. Preventive therapy of sickle pain is best achieved with hydroxyurea, which was found to decrease the frequency of crises significantly, decrease the incidence of acute chest syndrome, and decrease the need for blood transfusion.
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Curr. Opin. Hematol. · May 1995
ReviewGranulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in the treatment of myeloid leukemia.
Hematopoietic growth factors primarily used in patients with acute myelogenous leukemia after chemotherapy could reduce significantly the neutrophil recovery time in all patients. In high-risk acute myelogenous leukemia, trials also reported a reduction in the incidence of documented infections and early mortality rate. Thus in elderly patients with acute myelogenous leukemia and in high-risk patients with acute myelogenous leukemia the use of hematopoietic growth factors seems justified. ⋯ A novel strategy in the treatment of acute myelogenous leukemia is the attempt to increase the growth fraction of clonal leukemic cells prior to administration of chemotherapeutic agents by the administration of hematopoietic growth factors. Evidence shows that hematopoietic growth factors enhance anti-leukemic activity of cytosine arabinoside against leukemic cells by recruitment of leukemic cells into cell cycle, an increase of intracellular cytosine arabinoside triphosphate:deoxcytidine 5' triphosphate pool ratios, or by an enhanced cytosine arabinoside incorporation into the DNA of acute myelogenous leukemia blasts. Whether these mechanisms lead to an increase in the complete remission rate and eventually to an improvement in survival must be answered in ongoing larger acute myelogenous leukemia trials using granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor in such a setting.