Long-term treatment follow-up of children with sickle cell disease monitored with abnormal transcranial Doppler velocities

Stroke risk in sickle-cell-anemia (SCA) is predicted by high transcranial Doppler (TCD) velocities and prevented by chronic transfusions. Nevertheless, chronic transfusions are associated with severe side effects, such as iron overload. We present here the long-term follow-up of SCA-children from the newborn-CHIC-Creteil-cohort (1992-2012), detected at risk by TCD and placed on chronic transfusions. Patients with normalized-velocities and no persistent stenosis were treated with hydroxyurea, which had been shown to decrease anemia, and hemolytic rate, risk-factors for abnormal-TCD. They were followed with trimestrial Doppler and transfusions re-started immediately in case of reversion to abnormal-velocities. Patients with a genoidentical donor underwent transplantation. Abnormal-TCD (TAMMV≥200cm/sec) was detected in 92 SCA-children, at a mean age of 3.7 years/range:1.3-8.3. With a mean follow-up of 6.1 years, no stroke occurred post-transfusion. Normalization of velocities (TAMMV p = 0.001 ). Switch from transfusions to hydroxyurea was prescribed to 45 patients for a mean follow-up of 3.4 years. Reversion, predicted by baseline reticulocyte count ≥400×10 9 /L (HR=6.3,95%CI:1.8-21.7,p= 0.001 ), occurred in 13/45 (28.9%) at the mean age of 7.1 years/range:4.3-9.5. Transplantation, performed in 24 patients, allowed transfusions to be safely stopped in all patients and velocities to be normalized in 4 patients who still had abnormal-velocities on transfusions. This long-term cohort study shows that transfusions can be stopped not only in transplanted patients, but also in a subset of patients switched to hydroxyurea, provided trimestrial Doppler follow-up and immediately re-starting transfusions in case of reversion.