Patient groups according to initially applied treatment (n = 189). After a period without intensive therapy, 75 of 189 patients were placed on a transfusion program, 51 of them because of cerebral macrovasculopathy (TP1) (abnormal intracranial velocities [n = 49], intracranial stenosis [n = 2, in 1 patient with no available temporal window and in 1 patient with conditional TCD]), and 24 other patients because of frequent other complications in absence of any cerebral macrovasculopathy (TP2) (recurrent splenic sequestrations [n = 7], SCI in patients participating in the SIT Trial and randomized in the transfusion group [n = 3], frequent VOC and/or ACS and age younger than 3 years [n = 5], tricuspid regurgitant jet velocity (TRJV) higher than 2.5 m/s [n = 1], hip osteonecrosis [n = 5], and priapism [n = 3]). Thirty-one patients older than 3 years were treated with HU (n = 31) because of frequent VOC and/or ACS (n = 26) or severe anemia with baseline hemoglobin levels lower than 7 g/dL (n = 5). During follow-up, the transfusion program was stopped postsplenectomy (n = 1) and after normalization of intracranial velocities with absence of intracranial stenosis in patients refusing to take HU (n = 2). The transfusion program was replaced by HU in 31 patients after normalization of intracranial velocities and absence of intracranial (Ic) stenosis (n = 20), Ic stenosis regression (n = 1), history of frequent VOC and/or ACS in patients now older than 3 years (n = 2), postsplenectomy (n = 5), normalized TRJV (n = 1), end of SIT Trial (n = 2). However, 12 of them were placed again on a transfusion program because of HU failure to prevent VOC and/or ACS (n = 5), TRJV higher than 2.5 m/s (n = 3), abnormal TCD relapse, and/or intracranial stenosis occurrence (n = 4). At the end of follow-up (first MRI/MRA with cervical assessment), 86 patients still did not receive intensive therapy, 50 were receiving HU, and 53 were on a transfusion program.