Kwaku Ohene-Frempong, M.D., was born in Ghana and came to the United States in 1966 to attend Yale University. He received his Bachelor of Science degree in Biology in 1970 and was awarded the William Mallory Award for the Best Student Athlete at Yale. After graduating from the Yale School of Medicine in 1975, he trained in Pediatrics at the New York Hospital – Cornell Medical Center, and in Pediatric Hematology-Oncology (1977-80) at the Children’s Hospital of Philadelphia (CHOP). Following a 6-year service at Tulane University Medical Center, he returned to CHOP in 1986.
Dr. Ohene-Frempong has been involved in several research projects at the Comprehensive Sickle Cell Center at CHOP and is devoting an increasing amount of time to sickle cell disease work in Africa. In Ghana, he developed the first public health program for screening newborns for sickle cell disease in Africa. With assistance from the government of Brazil, he is working with Brazilian colleagues to scale up the newborn screening project into a national program and develop a Blood and Sickle Cell Center in Kumasi. Ghana launched its national newborn Screening Programme for Sickle Cell Disease in November 2010. Prof. Ohene-Frempong is serving as Programme Coordinator.
Dr. Ohene-Frempong is a Professor of Pediatrics at the University of Pennsylvania, Senior Scientist and Attending Hematologist, and Director Emeritus of the Comprehensive Sickle Cell Center at The Children’s Hospital of Philadelphia.
Abstract: Keeping patients well: a global view
Kwaku Ohene-Frempong, The Children’s Hospital of Philadelphia, USA
Newborns with sickle cell disease SCD, like those with other severe beta-hemoglobinopathies, are well and show no manifestation of the disease. From that moment on, clinical management follows a protocol largely of waiting for evidence of pathology and management of complications. Disease modifying therapies are for SCD are few and applied on a limited basis. The lives of most people with SCD are expectant not of improving but worsening health, disability, and of early death. This presentation will discuss current therapeutic approaches and propose a strategy for keeping most people with SCD well.
Disease-modifying therapies currently available are chronic transfusion (CTx), hydroxyurea (HU), and hematopoietic stem cell transplantation (HSCT). The overwhelming majority of people in the world with severe SCD (SS, So thal, SOArab), especially those living in resource-poor countries, do not receive these therapies or simple interventions such as penicillin prophylaxis and anti-pneumococcal vaccination. On the distant horizon are a few botanicals and pharmacologic agents on trial, and gene therapy for SCD may soon become a reality. CTx and HU therapies are restricted to patients who have demonstrated severe and often irreversible physical or psychological pathology, even as evidence supporting their broad effect on the disease continues to mount. Repeatedly, clinical trials involving CTx and HU therapies demonstrate their efficacy in modifying the basic clinical course of SCD however, application of these therapies continue to be targeted to only a minority of patients. Cost-effectiveness of CTx and HU therapy has been favorably demonstrated in SCD. Yet, health care providers tend to exaggerate the side effects, toxicities, and costs associated with these therapies, resulting in denial of access to many qualifying patients. In addition, patients and their families are insufficiently informed about the value of these therapies. In the end, SCD remains associated with reduced survival with more than 85% of the deaths related to the underlying disease.
Early diagnosis of SCD followed by anti-microbial prophylaxis is improving as newborn screening programmes grow in countries with highest incidence rates. In the next decade or two, very large numbers of young children, previously unidentified and unplanned for in public health services, will need to be provided specific treatment for SCD. Most of these children will be born in resource-poor, developing countries in Africa, India, and the Caribbean. Will the strategies for SCD management adopted in resource-rich countries apply in poor countries? Curative HSCT and “elegant” interventions such as gene therapy are expected to emerge and slowly expand in use. However, it is difficulty to envisage when the 6 million people with severe SCD (50% of the total estimated global SCD population) would have access to such interventions. Would not a strategy that aims to prevent most common acute complications be wiser, especially in areas where most patients are unlikely to reach full-service healthcare institutions in time?
There are very few people with severe SCD who have little or no chronic hemolytic anemia, do not encounter significant medical or psychosocial complications of the disease through the lifespan, and have normal survival. Most adults and children with severe SCD would benefit from hydroxyurea therapy; those who do not respond with significantly improved hemolytic anemia, clinical course, and health-related quality of life should be offered chronic transfusion therapy. That should be the standard approach to management of severe SCD in 2012 (SCD Scientific Year 102). Clinical research in SCD would shift to compare and improve these therapies and new interventions would be measured against this raised standard and not against placebo.