New considerations in the treatment of sickle cell disease.

The familial pattern of recurring pain and early death seen so often among those affected by sickle cell disease has been long recognized within African cultures, though its first clear description in Western medical literature did not appear until 1910 (1). Although most common in persons of African ancestry, the mutation giving rise to the sickle gene arose independently in several locations where malaria was prevalent (2), traveled with migrating populations, and is now widely distributed among regions and ethnic groups. Recognizing the qualitative abnormality of sickle hemoglobin as a prototype, Pauling & Castle established the notion of a molecular disease (3). Ironically, while the biochemistry and molecular biology of sickle cell disease has been intensively investigated, research into patient care has been limited in scope until recently. Prospective study of large patient groups diagnosed at birth is now providing insight into the disease's natural history and facilitating investigational treatments. Newborn diagnosis, combined with study of new drugs, cytokines, surgical procedures, and a more proactive utilization of transfusion is leading to greatly improved care and survival. Life expectancy is increasing (4) but adults are experiencing more complications of chronic organ dysfunction. A few patients have been cured by stem-cell transplantation, but difficult problems will continue to limit its application.