Faculty Bibliography

High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (HDT/ASCT) can improve survival in patients with lymphoma. Limited experience is available on the safety and efficacy of HDT/ASCT in elderly patients. In this article, we review the published data on the role of HDT/ASCT in management of lymphoma in older patients. Based on available data, evaluation of comorbidities, functional status, and comprehensive geriatric assessment (CGA) will help identify those who can benefit most from this intervention. Prospective clinical trials focusing on HDT/ASCT in older patients with lymphoma are needed to establish optimal management protocols in this select population.

Malaria is a serious and sometimes fatal disease caused by an intraerythrocytic parasite, and is commonly seen in developing countries. Approximately 1500 cases of malaria are diagnosed in the United States each year, mostly in travelers and immigrants returning from endemic areas [1]. There are many different regimens used to treat malaria, some of which are not approved in the USA. The side effects of these medications may not be familiar to physicians in the USA. We report a case of a returning traveler from Nigeria presenting with fever and hemolytic anemia caused by a delayed response to artesunate given 3 weeks earlier while in Nigeria. To our knowledge, there are few cases reported in the United States of hemolytic anemia secondary to artesunate therapy [2].

Neurofibromin (Nf1) is an approximately 280 kDa protein having tumor suppressor function, presumably by virtue of its GTPase activating domain, but little is known regarding molecular aspects of its effector pathways. Caveolin-1 (Cav-1) regulates diverse signaling molecules and has itself been implicated as a tumor suppressor. Here we demonstrate that Nf1 binds to Cav-1's scaffolding domain and co-immunoprecipitates with Cav-1. Analysis of Nf1's primary structure reveals four potential caveolin binding domains, and interestingly, in individuals with neurofibromatosis I, missense mutations occur with high frequency in 3 of the 4 putative domains. We show that Nf1 modulates ras, Akt, and focal adhesion kinase pathways, thereby affecting cytoskeletal organization; moreover, Nf1's effects on signaling are altered when lipid rafts and caveolae are disrupted by cholesterol depletion. These novel findings provide insight into possible signaling mechanisms of Nf1 and suggest that together Nf1 and Cav-1 may coordinately regulate cell growth and differentiation.