October 25, 2016
9 min read

Training, collaboration key to overcoming ‘inadequacies of care’ for sickle cell disease

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Outcomes for individuals with sickle cell disease have improved markedly in recent decades.

More than 90% of children in the developed world born with the inherited genetic condition — once synonymous with early childhood mortality — will live to adulthood.

However, the longer lifespans of patients with sickle cell disease have presented new challenges, such as a complicated transition to adult care and inconsistencies in the quality of care delivered.

Alexis A. Thompson

Additional problems persist in underdeveloped regions, such as India and sub-Saharan Africa, where sickle cell disease is common and childhood mortality remains high.

“The issues surrounding the treatment of patients with sickle cell disease fall into several categories,” Alexis A. Thompson, MD, MPH, head of hematology at Ann and Robert H. Lurie Children’s Hospital of Chicago, professor of pediatrics at Northwestern University Feinberg School of Medicine, and ASH vice president, told HemOnc Today. “First and foremost is the immense suffering and inadequacies of care for people who have sickle cell disease.”

ASH and other groups collaborated to issue the State of Sickle Cell Disease: 2016 Report, which outlines disparities in access to medical care, potential opportunities for research into new treatment options and strategies for training a new generation of treating physicians.

ASH — along with patient advocacy groups, researchers, industry stakeholders and policymakers — also announced the launch of Sickle Cell Disease Coalition to improve the quality of sickle cell disease care around the globe.

“We recognize that there are extraordinary opportunities that seem to be coming together right now, and it is going to be absolutely critical that we unify these opportunities to take maximum advantage and facilitate improvements in treatment for people with this disease,” Thompson said.

Access to care

Overcoming disparities in the diagnosis of sickle cell disease and inconsistent care delivery across countries and health care systems is key to improving treatment, outcomes and quality of life for patients with sickle cell disease.

“If we are talking about the United States, one of the major milestones of treatment is newborn screening combined with penicillin prophylaxis,” Thompson said. “Newborn screening, penicillin prophylaxis, immunization and other interventions have saved lives, and we can now say that 95% of U.S. children will live into adulthood. That has created some phenomenal opportunities, and we want to see those children reach their full potential.”

Despite universal newborn screening in the United States, research has shown that 31% of infants did not receive long-term follow-up after diagnosis.

Further, improvements in life expectancy have not been uniformly met with advances in treatment.

More than 75% of adults with sickle cell disease and frequent pain crises do not get hydroxyurea — the only FDA–approved sickle cell disease drug. When inadequately treated, sickle cell disease can cause debilitating pain, and these individuals remain at an increased risk for fatal adverse events, including stroke.

The high medical costs associated with the disease — approximately $1 million for patients who achieve a lifespan of 45 years, with annual costs of $10,000 for children and $30,000 for adults — may cause some patients to forgo necessary treatments they cannot afford.

“We need to understand more about why hydroxyurea is underutilized,” Thompson said. “If we understand the barriers, we can try to overcome them, because we know the benefits that hydroxyurea can impart on patients with sickle cell disease.”

Although the mortality rate among children with sickle cell disease decreased 3% annually from 1979 to 2005, the mortality rate among adults increased 1% per year during that time.

“There is a dramatic increase in the health care needs of people with sickle cell disease as they move into their 20s and 30s,” Thompson said. “Those who are living into adulthood are surviving longer, but their quality of life could be vastly improved.”


To address these issues, ASH recommended all health care facilities implement standard-of-care guidelines and develop new resources to help physicians who treat patients with sickle cell disease. Coordinated care models that incorporate community health workers also can help ensure consistency of care throughout more rural parts of the country.

Additional issues face children and adults in underdeveloped countries, where sickle cell disease remains a chronic and fatal childhood condition.

Sickle cell disease primarily occurs in malaria-endemic areas of the world, including the Middle East, Africa and South Asia. Between 10% and 40% of the populations in most African countries carry the sickle cell gene, resulting in a disease prevalence of at least 2%. Approximately 1,000 African children are born with sickle cell disease each day.

The survival gains observed in the United States and United Kingdom have not occurred in nations with fewer resources. Only 10% of African children with sickle cell disease will live to adulthood, and more than half will die by the age of 5 years.

“The mortality rate for children aged younger than 5 years is between 50% and 90% in these countries,” Thompson said. “There is a different set of priorities that needs to be addressed when we talk about the parts of the world with the largest number of patients.”

Increased use of newborn screening and better access to management therapies are essential for improving worldwide care of sickle cell disease, according to the report. The development of guidelines for areas with low resources is another need.

Physicians and organizations in the developed world may hold the key for the expansion of necessary diagnosis and treatment platforms globally, Thompson said.

“An opportunity exists to expand newborn screening to implement early interventions that have improved outcomes in middle- and high-income countries,” Thompson said. “There have been a number of pilot projects that demonstrate the feasibility of performing newborn screening in lower-resource countries. Penicillin and immunization are within the grasp of many countries, and being aware that a child has sickle cell enables a family, a community and a hospital to provide a heightened level of service to those children.”

Physician training

Adequate physician training and education are needed to implement sickle cell disease guidelines, transition patients from childhood to adult care, and increase the use of hydroxyurea in appropriate clinical situations.

Survey data show only 20.4% of family physicians felt comfortable treating patients with sickle cell disease. An additional 69.4% said that clinical decision support tools would help them in their decision-making for sickle cell disease, and 72.6% said more education and decision support tools would help them avoid complications in disease management.

“Primary care physicians, hospitalists, emergency physicians and even oncologists who have sickle cell patients in their practice benefit from having tools made available to them,” Thompson said. “Training and professional education also serve to improve the knowledge base. ASH and other professional societies have an opportunity to reach their memberships and incorporate sickle cell disease more seamlessly into professional education platforms.”

The transition from pediatric to adult medical care is a specific area where training and education are needed.

Although most children in the United States receive care in academic medical centers and have access to pediatric hematologists, adults are more likely to receive care in community hospitals, where there may not be sickle cell disease experts.

Goals outlined in the report include to increase the number of providers able to care for patients with sickle cell disease through training and certificate programs, cultivate an interest in the disease among those in medical training and develop clinical support tools.

Further, an actionable plan can be used to educate hematologists, PCPs, hospitalists and ED physicians about best practices.

“Improving the knowledge base for clinicians, patients and the community are ways that we think can improve access to care,” Thompson said. “The NHLBI expert panel report included evidence-based guidelines [for sickle cell disease], but there are far too few who are aware of them or using them. ASH has already converted large portions of that report into more convenient pocket guides, which are available on smartphones. Converting these data or presenting them in more approachable language for patients to read and understand is something we think is quite achievable.”


New research pathways

Few effective treatments exist for sickle cell disease, and the goal of treatment usually is to manage pain and complications.

Research goals outlined in the report include to identify predictors of the severity of the disease, optimize the use of existing therapies, develop novel and combination therapies, focus on pain research and strengthen curative therapies.

Several studies presented at the ASH Annual Meeting and Exposition in 2015 explored new treatments for sickle cell disease that may be “practice changing,” Thompson said.

A study by Ware and colleagues showed that treatment with the maximum-tolerated dose of hydroxyurea was noninferior to chronic red cell transfusions for stroke prevention in children with sickle cell anemia.

Another study, conducted in France, showed that matched-sibling hematopoietic stem cell transplantation extended OS and EFS in 90% of children with severe sickle cell disease, with limited complications or adverse events.

Lehrer-Graiwer and colleagues found that the oral small molecule hemoglobin modifier GBT440 (Global Blood Therapeutics) reduced hemolysis and improved anemia in patients with sickle cell disease, without increasing the risk for tissue hypoxia. This novel agent is moving forward to a phase 2 trial.

“It is a particularly exciting time in hematology, because there are several new medications in the pipeline for sickle cell disease, which is extraordinary,” Thompson said. “We think that being prepared and informing patients and their families about these opportunities is absolutely critical.”

There are 36 clinical trials underway to evaluate novel agents or approaches in treating sickle cell disease. However, many of these are industry-sponsored trials of single-agent drugs, and it may be years before these agents are widely available and affordable.

ASH is exploring the development of a clinical trial network to increase the number of patients on trials and allow for the evaluation of combination therapies. This also would enable the study of stem cell transplantation — which otherwise is limited due to high cost and availability of donors — and gene therapy.

Further, PCPs and hematologists should encourage their patients to volunteer for clinical trials to advance knowledge and treatment options.

“We are so excited about the possibility of having so many organizations come together to move this forward with a unified voice,” Thompson said. “We can take advantage of this opportunity to make a difference in the lives of individuals with sickle cell disease in the United States and around the world.” – by Cameron Kelsall


ASH. State of Sickle Cell Disease: 2016 Report. Available at www.scdcoalition.org/pdfs/ASH%20State%20of%20Sickle%20Cell%20Disease%202016%20Report.pdf. Accessed on Sept. 23, 2016.

The following were presented at the ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.:

Cappelli B, et al. Abstract 541.

Lehrer-Graiwer J, et al. Abstract 542.

Ware RE, et al. Abstract 3.

For more information:

Alexis A. Thompson, MD, MPH, can be reached at a-thompson@northwestern.edu.

Disclosure: Thompson reports a leadership role with ASH, as well as research funding from Amgen, Bluebird Bio, Eli Lilly and Mast Therapeutics.