Real‐Life experience with hydroxyurea in patients with sickle cell disease: Results from the prospective ESCORT‐HU cohort study

Abstract

Several controlled studies have evidenced good efficacy and short-term and midterm safety profiles for hydroxyurea (HU), which has become the cornerstone for prevention of sickle-cell disease (SCD)-related vaso-occlusive crises. However, there are few large-scale reports on its long-term use and certain caregivers and patients have concerns about its safety. Following the licensing of HU in Europe for children and adults with severe forms of SCD, ESCORT-HU was designed as a Phase IV observational cohort study. It included 1906 participants, of whom 55% were adults.The most common hemoglobin (Hb) genotypes were HbSS (84.7%) and HbSβ+ (7.0%). The median duration of follow-up was 45 months, for a total of 7309 patientyears of observation. The dose of HU after 1 year was 20.6 mg/kg/d for children and 16.3 mg/kg/d for adults. There was a statistically significant decrease in the number of vaso-occlusive episodes lasting >48 h, acute chest syndrome episodes, hospitalizations, and the percentage of patients requiring blood transfusions within the first 12 months relative to the year before enrolment. Neutropenia and thrombocytopenia were the most commonly reported adverse effects. No new HU toxicity was identified. Overall, 125 pregnancies were reported in 101 women and no malformations were observed in the neonates. There were 12 pregnancies for partners of male patients treated with HU. One case of fatal myelodysplastic syndrome was reported, for which a causal association with HU could not be excluded. This cohort study of patients with SCD highlights the positive benefit-to-risk ratio of HU in children and adults.

Incidence of cancer and related deaths in hemoglobinopathies: A follow‐up of 4631 patients between 1970 and 2021

“…and hydroxyurea have been considered as possible eventual causative factors, although there are no definitive findings so far. 30,31 Moreover, the largest lentiviral vector-mediated β-globin replacement gene therapy trial in SCD reported two cases of adult patients diagnosed with myeloid neoplasms, both considered unrelated to the gene therapy procedure, 32 as previously reported for patients with SCD undergoing BMT. 33,34 However, when we consider all hemoglobinopathies, BMT does not seem to be a major risk factor for cancer in our study, whereas the types of tumors detected in this group of patients indicate that the well-known risk of graft-vs-host disease-related cancers adds to that of a history of HCV and hepatic iron accumulation before BMT.…”

“…In this respect, a 72% increased risk of hematologic malignancies in patients with SCD in comparison with the general population was reported by Brunson et al 22 . Chronic inflammation and hydroxyurea have been considered as possible eventual causative factors, although there are no definitive findings so far 30,31 …”

Essential Thrombocythemia in Children and Adolescents

“…This, however, has not definitively been ascertained. Experience suggests that HU is efficient and safe in young adults with ET [ 93 ] and that it does not induce adverse effects on growth and fertility when used in children with sickle-cell anemia [ 94 ]. However, HU might have different (and detrimental) effects in lifelong treatment for patients with a clonal diseases such as ET.…”

Mathematical Modeling of Hydroxyurea Therapy in Individuals with Sickle Cell Disease

“…SCD affects approximately 100,000 people in the United States and millions globally, and every year an estimated 300,000 children are born with sickle cell anemia (SCA) across the globe [ 3 , 4 ]. Hydroxyurea (HU) is approved by the Food and Drug Administration for adults and children aged 2–18 years with SCD, but it is widely utilized in children beginning as early as 9 months of age [ 5 , 6 ]. Although HU has multiple therapeutic benefits in individuals with SCD, the primary benefits are through increasing fetal hemoglobin (HbF) and additionally increasing mean cell volume (MCV) and reducing absolute neutrophil count (ANC) and total white blood cell (WBC) counts.…”