Lower leukemia relapse in pediatric patients with pulmonary cytolytic thrombi following allogeneic transplant.

Pulmonary cytolytic thrombi (PCT) is an uncommon complication after hematopoietic cell transplantation. Although the pathogenesis is unknown, patients typically respond to systemic corticosteroid treatment. Considering corticosteroids may impair GVL reactions, we reviewed the records of 324 pediatric patients who received a transplant for leukemia and compared the outcomes of those with PCT (n=14) to those without PCT (n=310). PCT patients had a significantly more acute GVHD (aGVHD) and chronic GVHD (cGVHD). Though 3-year non-relapse mortality and OS were similar, there was significantly less relapse in patients with PCT compared to those without PCT (0 vs 28%, P=0.02), regardless of the presence or absence of aGVHD. In multivariate analysis, grade II-IV aGVHD (P=0.02), cGVHD (P=0.01) and development of PCT (P<0.01) were independently associated with less relapse. These data suggest that patients with PCT are at greater risk for GVHD, but at lower risk of leukemia relapse.

Lowering of HDL cholesterol in post-menopausal women by tibolone is not associated with changes in cholesterol efflux capacity or paraoxonase activity.

Low HDL cholesterol increases the risk of coronary heart disease. Treatment of postmenopausal women with tibolone lowers HDL cholesterol. We elucidated the consequences of this unwanted side effect in a randomized, double-blind study, where 12 women received 2.5 mg tibolone per day and 6 women, placebo. Blood samples were collected on days -1 (i.e. baseline), 28, 56, and 84 for the analysis of various parameters of lipid metabolism and HDL function. Compared to placebo, treatment with tibolone led to statistically significant decreases of HDL cholesterol (-22% to -32%), apoA-I (-14% to -22%), and HDL subclass LpA-I (-30% to -40%) but to no significant changes in apoA-II and HDL subclass LpA-I,A-II. These changes were not associated with statistically significant changes in the activity of plasma to release 3H-cholesterol from radiolabeled fibroblasts or in the serum activity of the anti-oxidative enzyme paraoxonase/arylesterase. There were no significant changes in either serum levels of triglycerides, LDL cholesterol, apoB, and leptin, or in LDL size. We conclude that changes in insulin do not contribute to the lowering of HDL cholesterol by tibolone. Despite decreased HDL cholesterol, putatively anti-atherogenic activities of HDL remained unchanged.

Treatment of hypertriglyceridemia by two diets rich either in unsaturated fatty acids or in carbohydrates: effects on lipoprotein subclasses, lipolytic enzymes, lipid transfer proteins, insulin and leptin.

BACKGROUND: There is lack of agreement on which dietary regimen is most suitable for treatment of hypertriglyceridemia, especially if high triglyceride concentrations are not due to obesity or alcohol abuse. We compared the effects on blood lipids of a diet high in total and unsaturated fat with a low-fat diet in patients with triglyceride concentrations of > 2.3 mmol/l. METHODS: Nineteen non-obese male outpatients with triglycerides ranging from 2.30 to 9.94 mmol/l received two consecutive diets for 3 weeks each: first a modified high-fat diet (39% total fat, 8% SFA, 15% monounsaturated fatty acids, 1.6% marine n-3 polyunsaturated fatty acids), and then a low-fat diet (total fat 28%, carbohydrates 54%). RESULTS: The high-fat diet significantly decreased triglycerides (-63%), total cholesterol (-22%), VLDL cholesterol (-54%), LDL cholesterol ( 16%), total apoC-III (-27%), apoC-III in apoB containing lipoproteins (apoC-III LpB; -31%) and in HDL (apoC-III nonLpB; -29%), apoE in serum (-33%) and apoB-containing lipoproteins (nonHDL-E; -42%), LpA-I (-16%), insulin (-36%), and leptin (-26%) and significantly increased the means of HDL cholesterol (+8%), LDL size (+6%), lipoprotein lipase (LPL, +11%), hepatic lipase (+13%), and lecithin: cholesterol acyltransferase (LCAT, +2%). The subsequent low-fat diet increased triglycerides (+63%), VLDL cholesterol (+19%), apoC-III (+23%), apoC-III LpB (+44%) apoC-III nonLpB (+17%), apoE (+29%) and nonHDL-E (+43%), and decreased HDL cholesterol (-12%), LPL (-3%), and LCAT (-3%). Changes in triglycerides correlated with changes in LPL activity and insulin levels. CONCLUSIONS: In hypertriglyceridemic patients, a modified diet rich in mono- and n-3 polyunsaturated fatty acids is more effective than a carbohydrate-rich low-fat diet in correcting the atherogenic lipoprotein phenotype.

Pulmonary cytolytic thrombi: a newly recognized complication of stem cell transplantation.

Over the past 5 years we have recognized a new pulmonary complication of hematopoietic stem cell transplantation (HSCT) associated with fever and pulmonary nodules termed 'pulmonary cytolytic thrombi' (PCT). Retrospective analysis of medical and radiographic records and pathologic material from 13 HSCT recipients with PCT and a review of the Blood and Marrow Transplant Database for all patients with radiographic evidence of pulmonary nodules or who underwent open-lung biopsy from 1 January 1993 to 31 December 1998 (n = 1228) were performed. The median age of patients with PCT was 11.9 years (range, 1.3-29.7 years). All patients developed fever at a median of 72 days (range, 8-343 days) post transplant, followed by pulmonary nodules on chest CT. Eleven patients were receiving therapy for active GVHD (acute, grades I-IV (n = 10); extensive chronic (n = 1)). Biopsy of the pulmonary nodules revealed a unique pattern of necrotic, basophilic thromboemboli with amorphous material suggestive of cellular breakdown products. This was descriptively labeled 'pulmonary cytolytic thrombi'. Immunohistochemical staining revealed entrapped leukocytes and disrupted endothelium, but was negative for histiocytes. Cultures and immunohistochemical stains were negative for infectious agents. Empiric therapy included systemic corticosteroids (n = 9) and amphotericin (n = 7). Nine patients survive with resolution of PCT at a median follow-up of 1.5 years. Bone Marrow Transplantation (2000) 25, 293-300.