Hydroxyurea for children with sickle cell anemia: Prescribe it early and often

Ware, Russell E.; McGann, Patrick T.; Quinn, Charles T.

doi:10.1002/pbc.27778

Cited by 20 publications

(17 citation statements)

References 16 publications

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“… 28 In addition, these studies have argued that an individualized dosage of HU based on pharmacokinetics represents a more efficient strategy than traditional weight-based dosing and stepwise escalation to MTD. 28 , 29 , 30 In the present study, our results demonstrated safety and favorable effects on the neutrophils of SCA patients using HU at higher doses.…”

Section: Discussionsupporting

confidence: 70%

Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship

Pedrosa

Leal

Lemes

2021

Hematology, Transfusion and Cell Therapy

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Introduction Although the efficacy of hydroxyurea (HU) in inhibiting erythrocyte sickling has been well demonstrated, the action of this drug on human neutrophils and the mechanism by which it improves the manifestations of the disease have not been studied thoroughly. We aimed to investigate the cell viability, along with inflammatory and oxidative markers in the neutrophils of sickle cell anemia (SCA) patients and the effects of HU therapy on these cells, by evaluating the dose-responsiveness. Methods In the present study, 101 patients (45 men and 56 women, aged 18–69 years) with SCA were divided into groups according to the use or not of HU: the SS group (without HU treatment, n = 47) and the SSHU group (under HU treatment, n = 54). The SSHU group was further stratified into subgroups according to the daily dose of the drug that patients already used: SSHU - 0.5 g (n = 19); SSHU - 1 g (n = 26) and SSHU - 1.5–2 g (n = 9). A control group (AA) comprised 50 healthy individuals. Neutrophils isolated from whole blood were analyzed using Trypan Blue, monoiodotyrosine (MTT) and lactate dehydrogenase (LDH) toxicity assays. Myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and concentrations of interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and malonaldehyde (MDA) were also measured. Results Neutrophils from SCA patients showed membrane fragility and a significant decrease in cell viability when analyzed by Trypan Blue ( p < 0.05), MTT ( p < 0.001) and LDH ( p = 0.011), compared to the AA group. Levels of inflammatory (MPO, TNF-α, and IL-10) and oxidative markers (SOD, GSH-Px, and MDA) were also altered ( p < 0.05) in these cells, showing a significant difference in the SSHU-1g and SSHU - 1.5–2 g groups, compared to the SS group. Treatment with HU reverted the levels of all markers to concentrations similar to those in healthy individuals in a positive dose-effect relationship. Conclusion The HU did not generate a cytotoxic effect on neutrophils in SCA patients, but it modulated their oxidative and inflammatory mechanisms, promoting cytoprotection with a positive dose-effect.

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Section: Discussionsupporting

confidence: 70%

Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship

Pedrosa

Leal

Lemes

2021

Hematology, Transfusion and Cell Therapy

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“…This practice change included education within our own team about the benefits and safety profile of hydroxyurea with careful review of the literature to support this change and to allow for a unified message about hydroxyurea to patients and families. As opposed to previous discussions describing hydroxyurea as an important medication to start when complications develop, our new approach involved discussions of hydroxyurea as a medication that can prevent complications and allow for a healthier and improved quality of life, much different than previous generations of patients with SCA 11,21 . We have also started these discussions at the first clinical visit as part of routine sickle cell education.…”

Section: Discussionmentioning

confidence: 99%

Implementation of near‐universal hydroxyurea uptake among children with sickle cell anemia: A single‐center experience

Karkoska

Todd

Niss

et al. 2021

Pediatric Blood & Cancer

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Background Without early initiation of disease‐modifying therapy, the acute and chronic complications of sickle cell anemia (SCA) begin early in childhood and progress throughout life. Hydroxyurea is a safe and effective medication that reduces or prevents most SCA‐related complications. Despite recommendations to prescribe hydroxyurea for all children with SCA as young as 9 months, utilization remains low. Procedure We completed a retrospective review of hydroxyurea‐prescribing practices and associated clinical outcomes at our institution over a 10‐year period before and after the 2014 National Heart, Lung, and Blood Institute (NHLBI) recommendations to use hydroxyurea for all children with SCA. Results Hydroxyurea use more than doubled within our pediatric SCA population from 43% in 2010 to 95% in 2019. The age of hydroxyurea initiation was significantly younger during 2014–2019 compared to 2010–2013 (median 2 years vs. 6 years, p ≤ .001). With this change in clinical practice, nearly all (69/71 = 97%) children born after 2013 received disease‐modifying therapy by the end of 2019, primarily hydroxyurea (93%). Concurrently, the number of SCA‐related admissions significantly decreased from 67/100 patient‐years in 2010 to 39/100 patient‐years in 2019 (p < .001). Conclusion The early and universal prescription of hydroxyurea for children with SCA is the standard of care. Here, we demonstrate that a careful and deliberate commitment to follow this guideline in clinical practice is feasible and results in measurable improvements in clinical outcomes. Our approach and improved outcomes can serve as a model for other programs to expand their hydroxyurea use for more children with SCA.

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“…64 Pediatric hematologists strongly recommend the use of HU in children with SCD early and frequently. 65 Unfortunately, access to specialist care for adolescents and adults with SCD is limited and associated with many barriers. Most important among these include appointment non-adherence.…”

Section: Amentioning

confidence: 99%

The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease

Ballas¹

2020

Mediterr J Hematol Infect Dis

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Sickle cell disease (SCD) is an extremely heterogeneous disease that has been associated with global morbidity and early mortality. More effective and inexpensive therapiesare needed. During the last five years the landscape of the pharmacotherapy of SCD has changed dramatically. Currently, there are at least 50 drugs that have been used or under consideration to use for the treatment of SCD. These fall into 3 categories: the first category includes the three drugs (Hydroxyurea, L-Glutamine and Crizanlizumab tmca) that have been approved by the United States Food and Drug Administration (FDA) based on successful clinical trials. The second category includes 22 drugs that failed, discontinued or terminated for now and the third category includes 25 drugs that are actively being considered for the treatment of SCD. New therapies targeting multiple pathways in its complex pathophysiology have been achieved or are under continued investigation. The emerging trend seems to be the use of multimodal drugs (i.e. drugs that have different mechanisms of action) to treat SCD similar to the use of multiple chemotherapeutic agents to treat cancer.

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Hydroxyurea for children with sickle cell anemia: Prescribe it early and often

Cited by 20 publications

References 16 publications

Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship

Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship

Implementation of near‐universal hydroxyurea uptake among children with sickle cell anemia: A single‐center experience

The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease

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