American journal of hematology
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Multicenter Study Clinical Trial
Rapid donor T-cell engraftment increases the risk of chronic graft-versus-host disease following salvage allogeneic peripheral blood hematopoietic cell transplantation for bone marrow failure syndromes.
The risk of graft-rejection after allogeneic hematopoietic cell transplantation using conventional cyclophosphamide-based conditioning is increased in patients with bone marrow failure syndromes (BMFS) who are heavily transfused and often HLA-alloimmunized. Fifty-six patients with BMFS underwent fludarabine-based reduced-intensity conditioning and allogeneic peripheral blood progenitor cell (PBPC) transplantation at a single institution. The conditioning regimen consisted of intravenous cyclophosphamide, fludarabine, and equine antithymocyte globulin. ⋯ The cumulative incidence of grade II-IV acute-GVHD and chronic-GVHD was 51.8% and 72%, respectively; with 87.1% surviving at a median follow-up of 4.5 years. A multivariate analysis showed pretransplant alloimmunization and rapid donor T-cell engraftment (≥95% donor by day 30) were both significantly (P < 0.05) associated with the development of chronic-GVHD (adjusted HR 2.13 and 2.99, respectively). These data show fludarabine-based PBPC transplantation overcomes the risk of graft-failure in patients with BMFS, although rapid donor T-cell engraftment associated with this approach appears to increase the risk of chronic-GVHD. (Clinicaltrials.gov identifier: NCT00003838).
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Impact of a venous thromboembolism prophylaxis "smart order set": Improved compliance, fewer events.
Venous thromboembolism (VTE) affects over 700,000 Americans annually. Prophylaxis reduces the risk of VTE by 60% but many patients still do not receive risk-appropriate VTE prophylaxis. To improve our institution's VTE prophylaxis performance, we developed mandatory computerized clinical decision support-enabled "smart order sets" that required providers to assess VTE risk factors and contraindications to pharmacologic prophylaxis. ⋯ Radiographically documented symptomatic VTE within 90 days of hospital discharge declined from 2.5% to 0.7% (P = 0.002). Preventable harm was completely eliminated (1.1% to 0%, P = 0.001) with no difference in major bleeding or all-cause mortality. A VTE prophylaxis computerized clinical decision support-enabled "smart order set" improved prescription of risk-appropriate VTE prophylaxis, reduced symptomatic VTE and eliminated preventable harm from VTE without increasing major bleeding.
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Polycythemia Vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) primarily characterized by erythrocytosis and thrombocytosis, respectively. Other disease features include leukocytosis, splenomegaly, thrombohemorrhagic complications, vasomotor disturbances, pruritus and a small risk of disease progression into acute myeloid leukemia or myelofibrosis. ⋯ Survival is near-normal in ET and reasonably long in PV. The 10-year risk of leukemic/fibrotic transformation is <1%/1% in ET and <3%/10% in PV. In contrast, the risk of thrombosis exceeds 20%. The main goal of therapy is therefore to prevent thrombohemorrhagic complications. In low risk patients, this is effectively and safely accomplished by the use of low-dose aspirin in both PV and ET and phlebotomy (hematocrit target of <45%) in PV. In high risk patients, treatment with hydroxyurea is additionally recommended, although not mandated in older patients without JAK2V617F or CV risk factors. Treatment with busulfan or interferon-α is usually effective in hydroxyurea failures. Screening for clinically significant AvWS is recommended before administrating aspirin in the presence of extreme thrombocytosis.