Low Fixed-Dose Hydroxyurea in Severely Affected Indian Children with Sickle Cell Disease

Abstract

There is limited data on the efficacy of hydroxyurea (HU) in Indian sickle cell anemia patients who have severe manifestations despite high fetal hemoglobin (Hb F). Sixty sickle cell anemia children (5-18 years) with more than three episodes of vasoocclusive crises or blood transfusions per year were randomized to receive HU (n = 30) or placebo (n = 30) therapy. Fixed dose (10 mg/kg/day) of HU was administered for 18 months and the patients were followed-up monthly with clinical assessment and laboratory monitoring. In the HU group, hemoglobin (Hb) and Hb F levels increased significantly along with a significant decrease in the number of painful crises, blood transfusion requirements and hospitalizations compared to the placebo group. No major adverse events were observed in this study. In conclusion, low-fixed dose HU therapy was effective for the treatment of Indian sickle cell anemia children. However, there is a need for long-term studies to evaluate the efficacy and toxicity in a larger number of Indian sickle cell anemia patients.

Update on the use of hydroxyurea therapy in sickle cell disease

“…15 A small RCT from India reported a significant decrease in the number of VOC, transfusion requirements, and hospitalizations with hydroxyurea compared with placebo despite high baseline HbF levels and low-dose therapy. 39 Findings from nonrandomized studies are consistent with those from RCTs in SCA, confirming decreased frequency of VOC, ACS, transfusion, and hospitalizations as well as overall safety of hydroxyurea in both children and adults. Furthermore, the long-term observational studies support the sustainability of effectiveness.…”

“…6,15,31,39,53 Thus, evidence gathered using other study designs substantially informs our recommendations. With the exception of the SWiTCH trial, these other RCTs described a benefit for patients receiving hydroxyurea compared with the standard of care.…”

“…In children, hydroxyurea was associated with decreased hospitalizations compared with placebo in 2 studies. 15,39 In adults and children, decreased rates of hospitalization were reported for BLOOD, 18 DECEMBER 2014 x VOLUME 124, NUMBER 26 HYDROXYUREA THERAPY 3851…”

“…Thirteen studies 6, [21][22][23][24][25][26][27][28][29][30][31][32] indicated a goal to increase to maximum tolerated dose (limited by mild myelosuppression), 5 studies increased until clinical or laboratory improvement was observed, [33][34][35][36][37] and 5 studies used fixed dosing at 10 or 20 mg/kg per day. 15,[38][39][40][41] When stated, all studies used a maximum dose of 30 to 35 mg/kg per day.…”

Clinical events in a large prospective cohort of children with sickle cell disease in Nagpur, India: evidence against a milder clinical phenotype in India

“…Individuals lost to follow‐up were censored. Patients were started on HU therapy if they were considered to have a severe phenotype as defined in the Multicenter Study of Hydroxyurea . Our planned comparison group was the CSSCD cohort, which was followed between 1978 and 1998, and preceded the general application of HU therapy.…”