This article is more than 5 years old. Information may no longer be current.
Sickle cell disease doubles risk for leukemia
Click Here to Manage Email Alerts
Individuals with sickle cell disease demonstrated more than double the risk for leukemia compared with the general population, according to an analysis of population-based data from California.
However, those with sickle cell disease did not demonstrate increased risk for most other cancers, and they had a reduced risk for solid tumors.
“To our knowledge, this is one of the first studies to determine cancer incidence among [patients with sickle cell disease],” Ted Wun, MD, FACP, director of UC Davis Clinical and Translational Science Center and chief of the division of hematology and oncology at UC Davis School of Medicine, and colleagues wrote. “The increased incidence of leukemia suggests a role of high cellular turnover and chronic inflammation in leukemic pathogenesis, and implies that mutations commonly seen in acute leukemia and myelodysplasia might be seen with greater frequency in patients with sickle cell disease.”
Life expectancy has improved among individuals with sickle cell disease in the past 50 years due to advances in treatment. Because more patients survive longer, their risk for cancer has increased.
Data on how cancer risk among individuals with sickle cell disease compares to the general population has been limited.
Wun and colleagues used databases from California’s Office of Statewide Health Planning and Development to identify 6,423 patients with sickle cell disease between 1991 and 2014.
Investigators used linked data from the population-based California Cancer Registry from 1988 through 2014 to determine cancer occurrence and calculate standardized incidence ratios (SIRs) to compare cancer incidence within the sickle cell disease cohort and the general population.
Researchers observed members of the sickle cell disease cohort for 141,752 person-years, with a median follow-up of 22.2 person-years. During follow-up, 115 individuals in the cohort received diagnoses of first primary cancers (median age at diagnosis, 46 years).
Results showed individuals with sickle cell disease did not have increased risk for a majority of cancer types; however, they demonstrated more than a twofold risk for leukemia.
When researchers analyzed risk by subtype, they determined the greatest risk was for acute myeloid leukemia (SIR = 3.59; 95% CI, 1.32-7.82). They also observed a borderline increased risk for chronic lymphocytic leukemia (SIR = 4.83; 95% CI, 1-14.11).
Females aged 15 to 39 years demonstrated a threefold increased risk for leukemia. Individuals with severe sickle cell disease — regardless of sex — demonstrated a fourfold increased risk for leukemia.
People with sickle cell disease demonstrated a 72% increased risk for hematologic malignancies compared with the general population.
Researchers observed a 38% reduced risk for solid tumors, which could be attributed to the sickling of red blood cells. Specifically, researchers observed reduced risks for breast cancers and male genital cancers, including cancers of the prostate, penis and testes.
Wun and colleagues acknowledged potential limitations of the study, including the absence of population data that included important variables — such as socioeconomic status — that could have impacted the cancer incidence rates.
“Further studies are needed to confirm our findings in a larger population and identify risk factors for developing cancer among [patients with sickle cell disease] and the impact on survival,” the researchers wrote. – by Melinda Stevens
Disclosures: The researchers report no relevant financial disclosures.
Perspective
Back to Top
Brunson and colleagues describe an increased risk for leukemia among patients with sickle disease in California. The standard incidence ratio (SIR) for leukemia was primarily increased among adolescents to young adults ages 15 to 39 years, and adults aged over 40 years.
The highest SIR — although not statistically significant — was for CLL (SIR = 4.83), which possibly reflects better care for patients with sickle cell disease, leading to a longer lifespan in an older age group in which CLL is more commonly seen.
Hydroxyurea, the mainstay of therapy in sickle cell disease, did not seem to increase leukemia risks. The SIR for leukemia from 1988 to 1999 — a span during which hydroxyurea was not frequently used — and the SIR from 2000 to 2014, after FDA approval of hydroxyurea, was similar. Further, patients with sickle cell disease had reduced risks for breast cancers and other solid tumors.
This is a provocative observation in a small subset of patients.
The possibility that inflammation, oxidative stress, iron overload and increased cell turnover plays a role in the increased risk for AML is intriguing and requires further study.
Click Here to Manage Email Alerts