PubMed · 16998958
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Ivan Oransky. 2006-09-09. Joan Wright Goodman.. https://doi.org/10.1016/s0140-6736(06)69358-6
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BACKGROUND: Despite decreases in overall mortality following bone marrow transplantation (BMT), a number of complications such as neurotoxicity have been described and often associated with immunosuppressive agents. The syndrome of reversible posterior leukoencephalopathy has been described in patients receiving cyclosporin and FK-506. We report here a subset of children who developed a syndrome of previously undescribed irreversible leukoencephalopathy following allogeneic BMT. PATIENTS AND METHODS: Between 1996 and 2002, 138 pediatric patients received an allogeneic BMT at Lucile Salter Packard Children's Hospital at Stanford. Six cases of irreversible leukoencephalopathy were observed. Cases were defined as children who exhibited progressive and continued, severe neurologic deterioration lasting greater than 2 weeks and consistent with non-localizing, central nervous system abnormalities. Medical records and magnetic resonance images (MRIs) were reviewed. RESULTS: Median age of the affected patients at BMT was 7.8 years. All six received cyclosporine, and [corrected] one had elevated drug levels. Encephalopathy occurred at a median of 53 days (range 14-77) following BMT. Symptoms at onset of leukoenceophalopathy included confusion and altered mental status, sluggish pupillary responses, abnormal movements, and seizures. Two patients died during their neurologic decline. Four patients remain alive with persistent encephalopathy. MRI showed abnormalities in all patients including periventricular or subcortical white matter involvement in all, and basal ganglia lesions in three. CONCLUSIONS: We report a syndrome of irreversible neurologic deficits and cerebral white matter abnormalities following allogeneic BMT, yet not associated with elevated cyclosporin levels. A precise mechanism for this syndrome is lacking and warrants further consideration.
Cardiac stem cell therapy with bone-marrow-derived stem cells is a promising approach to facilitate myocardial regeneration after acute myocardial infarction or in congestive heart failure. The clinical data currently available seem to indicate that this approach is safe and is not associated with an increase in the number of adverse clinical events; nevertheless, the level of safety confidence is limited because of the small number of patients who have been treated and the absence of long-term clinical follow-up data. In order to establish the clinical safety of cardiac stem cell therapy, it will be necessary to collect additional data from both previous and ongoing clinical trials in subsets of patients relative to their background risk. Several conceptual safety concerns should also be addressed. These concerns relate to a number of operational mechanisms and include biological effects on differentiation, remote homing of transplanted stem cells, progression of atherosclerosis, and arrhythmias. The proactive scrutiny of these phenomena could eventually facilitate the translation of the promise of cardiac regeneration into a safe and effective therapy.