Marrow reticulin was studied by trephine biopsy in 44 patients with adult acute leukaemia at presentation and subsequently during the course of their illness. The findings indicate that: (1) an increase in marrow reticulin is common at presentation in patients with both acute lymphoblastic and acute non-lymphoblastic leukaemia; (2) effective anti-leukaemic therapy results in resolution of some or all of the increased marrow reticulin and is not contraindicated, even in patients with a marked increase in marrow reticulin; and (3) reappearance of an increase in marrow reticulin may be a sign of relapse of the leukaemia.
Summary Aim: To compare clinical outcomes in a randomised comparison of treatment with danaparoid sodium (a heparinoid), or dextran 70, for heparin-induced thrombocytopaenia (HIT) plus thrombosis. Methods: Forty-two patients with recent thrombosis and a clinical diagnosis of probable HIT who presented at ten Australian hospitals during a study period of six and one half years were randomly assigned to open-label treatment with intravenous danaparoid or dextran 70, each combined with oral warfarin. Thirty-four patients (83%) had a positive platelet aggregation or 14C-serotonin release test for HIT antibody. Twenty-five received danaparoid as a bolus injection of 2400 anti-Xa units followed by 400 units per hour for 2 h, 300 units per hour for 2 h, and then 200 units per hour for five days. Seventeen received 1000 mL dextran 70 on day one and then 500 mL on days 2-5. Patients were reviewed daily for clinical evidence of thrombus progression or resolution, fresh thrombosis or embolism, bleeding or other complications. The primary trial endpoint was the proportion of thromboembolic events with complete clinical resolution by the time of discharge from hospital. Results: With danaparoid, there was complete clinical recovery from 56% of thromboembolic events compared to 14% after dextran 70 (Odds Ratio 10.53, 95% Confidence Interval 1.6–71.4; p = 0.02). Clinical recovery with danaparoid was complete or partial in 86% of thromboembolic events compared with 53% after dextran 70 (Odds Ratio 4.55, 95% Confidence Interval 1.2–16.7; p = 0.03). Overall clinical effectiveness of danaparoid was rated as high or moderate in 88% of patients compared with 47% for dextran 70 (p = 0.01). One patient given danaparoid died of thrombosis compared with three patients given dextran 70. The platelet count returned to normal after a mean of 6.7 days with danaparoid and 7.3 days with dextran 70. There was no major bleeding with either treatment. Conclusion: danaparoid plus warfarin treatment for HIT with thrombosis is effective, safe, and superior to dextran 70 plus warfarin.
Purpose: To determine the effect of curcumin on plasma cells and osteoclasts in patients with MGUS. Experimental Design: Twenty-six patients with MGUS were recruited into the study and administered 4 grams/day oral curcumin. Blood and urine samples were collected at specified visits after initiating therapy. Full blood count, B2 microglobulin, serum paraprotein, and immunoglobulin electrophoresis (IEPG and EPG) were determined for all patients at each visit. Serum calcium, 25 hydroxyvitamin D3, and bone-specific alkaline phosphatase were determined at baseline only. Urine, as a morning second-void sample, was collected at each visit for urinary N-telopeptide of type I collagen. Results: Our results show that oral curcumin is able to decrease paraprotein load in a select group (i.e., those having a paraprotein level of >20 g/L) of patients with MGUS. Fifty percent (5 of 10) of these patients had a 12% to 30% reduction in their paraprotein levels, while on curcumin therapy. In addition, 27% of patients on curcumin had a >25% decrease in urinary N-telopeptide of type I collagen. Conclusion: Due to the possible progression of MGUS to multiple myeloma, the potential role of curcumin as a therapeutic intervention for MGUS patients warrants further investigation. (Clin Cancer Res 2009;15(18):5917-22) Plasma cell dyscrasias, most commonly associated with paraproteinaemia, are a diverse group of disorders that includes multiple myeloma, Waldenstrom's macroglobulinaemia, heavy chain disease, monoclonal gammopathy of undefined significance (MGUS), and immunocytic amyloidosis. The incidence of plasma cell dyscrasias is age related, occurring in 1% of persons over age 25 years and 4% of those over age 70 years.MGUS is the most common of the monoclonal gammopathies. At Mayo Clinic, almost 60% of patients with a monoclonal gammopathy have MGUS (1). MGUS can precede multiple myeloma and is typified by a serum M-protein value of <30 g/L, fewer than 10% plasma cells in the bone marrow, no or a small amount of M protein in the urine, and absence of lytic bone lesions, anemia, hypercalcemia, or renal insufficiency related to the plasma-cell proliferative process (1). Myeloma is a progressive neoplastic disease and is characterized by high bone turnover, significant bone loss, and pathologic fractures resulting in significant morbidity and a high mortality. It is also associated with hypercalcemia, anemia, renal damage, and increased susceptibility to bacterial infections.Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover. Although MGUS is largely considered a benign condition, a number of studies show that patients with MGUS are at increased risk of developing fractures even before progression to myeloma (2).Elevated bone turnover is an independent predictor of fracture risk, and a number of studies have shown elevated bone resorption and/or reduced bone formation among patients with MGUS and myeloma (3, 4). A study by Diamond et al. (5) found that in a...
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