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Environmental, genetic factors may predict longevity in sickle cell disease

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October 17, 2016

A case series of individuals with sickle cell disease who lived into their ninth decade revealed potential genetic and environmental factors associated with their longevity.

The case report — published in Blood — included data from four women with sickle cell disease who have lived longer than age 80 years. Three women are American and received treatment at Thomas Jefferson University’s Sickle Cell Center. The fourth woman resided in Brazil.

Samir K. Ballas

One patient remained alive and in her 80s at the time of reporting. The remaining three patients are deceased and had lived into their 80s.

Although individuals with sickle cell disease are living longer than ever, most patients do not live beyond the age of 60 years, according to Samir K. Ballas, MD, FACP, emeritus professor of medicine and pediatrics at Thomas Jefferson University.

“In the 1990s, the average lifespan of a patient with sickle cell disease was between 40 years and 50 years,” Ballas told HemOnc Today. “In our patient population, we see a growing number of patients living well into their 50s, with some living into their 60s. In the long run, we hope that patients with sickle cell disease will approach a normal life span.”

Ballas and colleagues sought to observe common traits among patients with sickle cell disease who survive well beyond the average life span. The researchers observed that all octogenarian patients were women.

“On average, women with sickle cell disease live between 8 years and 10 years longer than men,” Ballas said.

The researchers further noted that all octogenarian patients had little history of vaso-occlusive pain crises and no history of strokes. The U.S. patients had no history of acute chest syndrome, although the Brazilian patient had a history of this condition.

Ballas and colleagues further noted that all of the octogenarian patients had low white blood cell counts, low hemoglobin levels and normal biochemical parameters. They also had no history of hydroxyurea use.

All octogenarian patients had several lifestyle factors in common, including no history of smoking; little to no history of alcohol consumption; excellent adherence to medication, medical appointments and patient referrals; and normal or below-normal BMI.

“All patients had excellent family support, which in turn may be responsible for their excellent treatment adherence,” Ballas said. “We believe that this contributed to their longevity, in addition to maintaining healthy lifestyles.”

The researchers acknowledged that their observations are anecdotal. However, Ballas asserted that physicians treating patients with sickle cell disease should consider initiating conversations about potentially actionable lifestyle factors.

“The message of our findings is to emphasize the environmental factors,” Ballas said. “These factors can be controlled or treated. We should counsel, advise and educate patients to follow the examples of these long-living individuals with sickle cell disease, all of whom achieved a life span beyond what is expected of the general population.” – by Cameron Kelsall

For more information:

Samir K. Ballas , MD, FACP, can be reached at samir.ballas@jefferson.edu.

Disclosure: The researchers report no relevant financial disclosures.

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PERSPECTIVE
Kathryn L. Hassell, MD

Kathryn L. Hassell

Sickle cell disease is a group of hemoglobinopathies characterized by lifelong hemolytic anemia and vaso-occlusive processes that lead to acute and chronic organ damage. This results in premature mortality, with an average age at death of 40 to 45 years in the United States for those with HbSS, or sickle cell anemia, the most severe form of the disease. Surveillance data from Georgia and California confirm this premature mortality but also identify an underrecognized subset of the sickle cell disease population that lives into the eighth or ninth decades of life.

The case series by Ballas and colleagues describes four octogenarians, including two with sickle cell anemia. Although anecdotal in nature, this study highlights in these elders the clinical features predicted to be associated with reduced severity of disease as observed in cohort studies of children and younger adults, such as the Cooperative Study of Sickle Cell Disease. These factors included constitutively elevated hemoglobin F, normal baseline white blood cell count, infrequent health care visits for acute severe vaso-occlusive pain episodes — or “crises” — and relatively low baseline hemoglobin values. These characteristics were present “naturally” in the patients reported by Ballas and colleagues, without lifelong application of disease-modifying therapies, such as hydroxyurea or sustained chronic transfusion therapy.

This study underscores and reinforces the enthusiasm for therapies that have the potential to target similar changes for all individuals with sickle cell disease. For example, hydroxyurea — the only FDA–approved therapy for sickle cell anemia — increases fetal hemoglobin, decreases white blood cell count, and is associated with fewer acute severe vaso-occlusive complications and improvement in survival.

However, more lessons will be learned by a larger study of individuals with sickle cell disease who survive decades beyond the average age of death. There likely are biological and environmental influences on disease course and survival that will be revealed only by methodical study of this portion of the population. Ongoing work — including the Sickle Cell Disease Data Collection program, supported by the CDC Foundation — has the potential to identify and scrutinize factors associated with longevity in sickle cell disease. In an era when the availability of curative therapies — including stem cell transplantation and gene-correction strategies — are still limited, analysis of long-term survivors can inform interventions and therapeutics for this devastating disease.

References:

CDC. Sickle Cell Data Collection Program. Available at: www.cdc.gov/ncbddd/hemoglobinopathies/scdc.html. Accessed on Nov. 28, 2016.

McGann PT and Ware RE. Expert Opin Drug Saf. 2015;doi:10.1517/14740338.2015.1088827.

Paulukonis ST, et al. Public Health Rep. 2016;131:367-375.

Serjeant GR. Cold Spring Harb Perspect Med. 2013;doi:10.1101/cshperspect.a011783.


Kathryn L. Hassell, MD

University of Colorado School of Medicine

Disclosure: Hassell reports no relevant financial disclosure.