Risk of SCD-related organ damage increases as teens become adults

Data suggest that early treatment with hydroxyurea may prevent damage

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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The probability of developing organ and tissue damage — including in the lungs, kidneys, or eyes — increases as teenagers with sickle cell disease (SCD) transition from adolescence into adulthood, according to a study by researchers in France.

Particularly, the study demonstrated that disease morbidity associated with chronic organ damage was higher when treatment with hydroxyurea, an approved SCD therapy, was started after the recurrence of vaso-occlusive complications.

“Our data suggest that the implementation of early preventive [hydroxyurea] treatment … may help to prevent chronic organ damage in patients with [more severe] genotypes,” the researchers wrote.

The study, “High risk of progression for chronic major organ complications of sickle cell disease in adolescents and young adults: A long-term neonatal cohort study,” was published as a letter to the editor in the American Journal of Hematology.

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Higher hemoglobin levels tied to lower end-organ damage risk

Probability of starting hydroxyurea rose from 49% to 68% over 10 years

SCD is caused by mutations in the beta-globin (HBB) gene, which contains instructions to make a component of hemoglobin — the protein that carries oxygen throughout the body.

Defective hemoglobin causes red blood cells to take on a sickle-like shape, making it difficult for them to pass through small blood vessels. Sickled red blood cells can slow and even obstruct blood flow, compromising oxygen delivery to body tissues and causing painful vaso-occlusive crises (VOCs). These abnormally shaped cells also are more prone to die prematurely, leading to a shortage of red blood cells in the body.

Chronic red blood cell destruction, along with oxygen deprivation brought on by repeated VOCs, ultimately leads to organ injury, which usually starts during childhood.

Now, a team of researchers sought to further understand the risk of chronic organ damage in patients ages 15-25. To that end, the researchers retrospectively analyzed clinical data from 150 patients who had been identified from their newborn screening cohort at the Créteil Hospital, in France.

The patients were divided into three main groups, with the largest, comprising 113 patients, counting those with more severe disease: 107 with HbSS and six with HbS/beta-zero-thalassemia. A total of 10 patients had HbS/beta-plus thalassemia, while 27 had HbSC.

HbSS patients have both mutated HBB gene copies producing a faulty version of hemoglobin called hemoglobin S, while HbSC patients have one gene copy that produces hemoglobin and another that encodes hemoglobin C, another defective form of the protein. Patients with the HbS/beta thalassemia disease subtypes, meanwhile, also have an HBB mutation that’s associated with beta thalassemia, a blood disorder that reduces hemoglobin production. While patients with beta-plus thalassemia can still produce low amounts of beta-globin, those with beta-zero are not able to produce any at all.

Consistent with other studies, the probability of the patients living until age 25 was high, at 94.9%.

Overall, the probability of starting treatment with disease-modifying therapies increased with age. For instance, the probability of initiating treatment with hydroxyurea increased from 49.1% at age 15 to 68.3% at age 25.

In 21 patients with the most severe disease types — HbSS/beta-zero thalassemia — hydroxyurea was started after the age of 15. In 16 of these patients, treatment was initiated for recurrent acute vaso-occlusive complications.

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Most patients are free from VOEs after gene therapy treatment

Risk of organ damage increases for patients from age 15 to 25

The probability of experiencing some organ complications also climbed with age. Specifically, the risk for high tricuspid regurgitation velocity (TRV), a feature associated with a higher probability of developing pulmonary hypertension — a disease marked by high blood pressure in the blood vessels that supply blood to the lungs — increased from 2.5% at age 15 to 13% at age 25 for all patient groups.

This was mainly associated with low levels of fetal hemoglobin, a form of hemoglobin produced during fetal development that is more effective at transporting oxygen in the body than its adult counterpart.

We report a high risk of progression for chronic … major organ complications of SCD throughout adolescence and early adulthood. … A focused ‘transition program’ to ensure the safe transfer of teenagers from pediatric to adult services should, therefore, be a key priority, to facilitate screening for chronic organ dysfunction.

The risk of SCD-related kidney complications was assessed based on the likelihood of developing albuminuria, or excessive levels of the protein albumin in the urine. This increased as patients got older, and was significantly higher in those with severe disease, the data showed.

Eye issues, more specifically retinopathy — a condition that can cause blindness and is triggered by damage occurring in blood vessels at the back of the eye — also were more frequent in older patients and among those with the HbSC genotype.

“We report a high risk of progression for chronic … major organ complications of SCD throughout adolescence and early adulthood,” the researchers wrote. “A focused ‘transition program’ to ensure the safe transfer of teenagers from pediatric to adult services should, therefore, be a key priority, to facilitate screening for chronic organ dysfunction,” the researchers wrote.