Abstract
BACKGROUND
HU (Hydroxycarbamide or Hydroxyurea) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and approved since 2007 in the European Union (EU) and 2017 in the Unites States of America (USA) for preventing vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in adults, adolescents and children ≥2 years with sickle cell disease (SCD). One risk raised for using a cytotoxic drug such as HU in children would be a potential negative impact on growth. Hence, a continuous follow-up of the growth of children treated with HU is recommended.
We hypothesized that as HU increased hemoglobin concentration and enhances quality of life it may have a positive impact on growth and even more significantly improve growth and nutritional status in SCD children, who are exposed by their disease to impaired growth due to higher metabolic rate, chronic anemia, and hypoxemia.
Here, we present preliminary results on growth development of sickle cell (SC) children enrolled in the ESCORT-HU study (European Sickle Cell Disease COhoRT - HydroxyUrea), a multicentric, prospective, non-interventional European study whose objective is to evaluate the safety of HU in real life.
METHOD
Between January 2009 and June 2017, 1920 patients were enrolled from 63 centers in France, Germany, Greece and Italy. Of these 1920 patients, 849 (408 girls and 441 boys) were < 18 years of age.
Patients' follow-up in ESCORT-HU is strictly observational and follows usual recommendations and local clinical practices. Patients are seen by their physician approximately every 3 to 6 months. Weights, heights and Body Mass Index (BMI) were thus collected all along the study.
Patients previously treated with HU and HU-naïve before inclusion have been included in ESCORT-HU study which allowed comparison of these two groups of patients at inclusion in the study.
The French population reference measurement scale (growth curve AFPA -CRESS/INSERM) was used for comparison of growth in children enrolled in ESCORT-HU as approximately 83% of children were included in France.
RESULTS
547 children with reported height and/or weight were HU-naive at inclusion and 292 children were non-HU naive. Non-HU naïve patients had been treated for a median of 4.56 ± 3.29 years before inclusion in the ESCORT-HU cohort.
Median duration of observation in the ESCORT-HU study was 2.60 ± 1.67 years
Data on HU treatment and SC genotypes (90% SS) are displayed in table 1.
Both heights and weights between HU-naive and non-HU naive girls and boys at enrolment were significantly different (p<0.001) (table 2 and 3). Non-HU naive girls and boys were taller and heavier compared to HU-naive patients, suggesting a positive impact of HU on growth.
Mean heights and weights per age for girls were within the normal range all along the study with a mild decrease between 12 and 14 years old (Figure 1 and 2). For boys, weights and heights were within the normal range until the age of 11 and below the median normal range after 11 years (Figure 3 and 4).
Mean BMIs stayed within the normal range for all age groups (Figure 5 and 6) during the course of treatment with HU. 12% of HU naive patients had a low BMI at enrolment but this percentage decreased constantly all along HU treatment (7.2% at year 2 and 3% at year 5). On the contrary, 6% of the patient were overweight (BMI above the normal range) and this percentage increased all along HU treatment (9.9% at year 2 and 15.8% at year 5). Among overweight patients, only seven were reported to have obesity and the percentage remained stable.
CONCLUSION
In the ESCORT-HU study children who were non HU-naive at enrolment were heavier and taller than HU-naive patients, but these differences faded during the course of HU treatment which confirmed the absence of negative impact of HU on growth.
Heights and weights were within the normal range for girls whereas boys seemed to have a slower growth from 12 years of age. This difference may be due to pubertal delay in boys, but pubertal status was not collected in ESCORT-HU so this data could not be analysed. A minority of pediatric patients experienced overweight, suggesting to screen this possible complication.
Oevermann:Addmedica: Membership on an entity's Board of Directors or advisory committees. De Montalembert:Addmedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy. Brousse:Addmedica: Membership on an entity's Board of Directors or advisory committees. Pondarré:Blue Bird Bio: Honoraria; Novartis: Honoraria; Addmedica: Membership on an entity's Board of Directors or advisory committees.
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