Dyslipidemia and lipid-lowering treatment in a hematopoietic stem cell transplant cohort: 25 years of follow-up data.

BACKGROUND: Dyslipidemia is common after hematopoietic stem cell transplantation (HSCT). Few data regarding the time course of lipid profiles after HSCT, the effect of multiple transplantations, and efficacy and safety of lipid-lowering treatments are available. OBJECTIVE: The objective of the study was to determine the prevalence and treatment of dyslipidemia over a 25-year period in a large, single-center cohort. METHODS: One thousand one hundred ninety-six adult patients (≥16 years) who underwent HSCT during 1973 to 2013 and who survived ≥100 days were studied retrospectively. RESULTS: The prevalence of dyslipidemia before transplantation was 36% and 28% in the autologous and allogeneic groups, respectively (P < .001). Three months after HSCT, the prevalence rose to 62% and 74% (P < .001), and at 25 years, it was 67% and 89%. Lipid profiles were similar after first and subsequent transplants. Baseline dyslipidemia (odds ratio [OR] = 2.72), allogeneic transplant (OR = 2.44), and age ≥ 35 years (OR = 2.33) were independent risk factors for dyslipidemia at 1 year. Lipid-lowering treatment was given to 223 (19%) patients, primarily in the form of statins (86%) and was associated with a decrease in total cholesterol from 246 to 192 mg/dL (P < .01) and from 244 to 195 mg/dL (P < .001) in the autologous and allogeneic groups, respectively. There were 10 cases (4%) of muscle symptoms prompting cessation of lipid-lowering therapy, including 1 case of rhabdomyolysis. The OR for dyslipidemia among patients who suffered a cardiovascular event (conditional logistic regression) was 3.5 (95% confidence interval = 1.6-7.7, P = .002). CONCLUSION: This study confirms that dyslipidemia is a common and long-lasting phenomenon among both allogeneic and autologous HSCT patients. Statins are effective, generally well-tolerated and should be highly recommended for the management of post-HSCT dyslipidemia.

Overexpression of α-synuclein in oligodendrocytes does not increase susceptibility to focal striatal excitotoxicity.

BACKGROUND: Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disease characterized by α-synuclein (α-syn) positive oligodendroglial cytoplasmic inclusions. The latter are associated with a neuronal multisystem neurodegeneration targeting central autonomic, olivopontocerebellar and striatonigral pathways, however the underlying mechanisms of neuronal cell death are poorly understood. Previous experiments have shown that oligodendroglial α-syn pathology increases the susceptibility to mitochondrial stress and proteasomal dysfunction leading to enhanced MSA-like neurodegeneration. Here we analyzed whether oligodendroglial α-syn overexpression in a transgenic mouse model of MSA synergistically interacts with focal neuronal excitotoxic damage generated by a striatal injection of quinolinic acid (QA) to affect the degree of striatal neuronal loss. RESULTS: QA injury led to comparable striatal neuronal loss and optical density of astro- and microgliosis in the striatum of transgenic and control mice. Respectively, no differences were identified in drug-induced rotation behavior or open field behavior between the groups. CONCLUSIONS: The failure of oligodendroglial α-syn pathology to exacerbate striatal neuronal loss resulting from QA excitotoxicity contrasts with enhanced striatal neurodegeneration due to oxidative or proteolytic stress, suggesting that enhanced vulnerability to excitotoxicity does not occur in oligodendroglial α-synucleinopathy like MSA.