This is a pilot, single-blind, randomized, multicenter, therapeutic clinical trial designed to evaluate the feasibility of enrolling infants and toddlers (9 months to 36 months) with sickle cell anemia (SCa; HbSS or HbSB0thalassemia), regardless of disease severity, to a therapeutic trial. The BaBY HuG trial demonstrated that a fixed dose (20 mg/kg/day) of hydroxyurea was safe and effective in decreasing SCa-related complications in very young children (9-18 months), and largely due to these findings, hydroxyurea is recommended to be offered to all children ( 9 months old) with SCa, independent of disease severity. nevertheless, children in the treatment arm of BaBY HuG continued to experience vaso-occlusive symptoms and to incur organ damage. in clinical trials of older children with SCa, intensification of hydroxyurea to a maximum tolerated dosage (MTD), defined by mild to moderate myelosuppression, may be associated with improved laboratory parameters compared to fixed lower-dosing, but the clinical benefits gained from dose intensification have not been described. Therefore, in the HuGKiSS trial, children in the standard treatment arm will receive a fixed dose of hydroxyurea (20mg/kg/day), and participants in the experimental arm will receive hydroxyurea intensified to MTD, defined by a goal absolute neutrophil count (anC) of 1500-3000 cells/[MiCRo-SYMBoL]L. This trial aims to establish a multicenter infrastructure that will identify, enroll and randomize very young children (9-36 months) to receive fixed dose versus intensified-dose hydroxyurea in a single blinded manner, and to obtain prospective pilot data comparing the clinical and laboratory outcomes between the treatment arms to facilitate design of a definitive phase iii trial.