Select patients with sickle cell anemia can safely stop transfusions

Children with sickle cell anemia and normalized transcranial Doppler velocities on transfusions appeared able to safely switch to hydroxyurea with trimestriel Doppler follow-up, according to long-term follow-up data.

Further, receipt of allogeneic transplant led to transfusion cessation in all patients, even those with abnormal velocities prior to transplant.

Children with sickle cell anemia and high risk for stroke — determined by high transcranial Doppler (TCD) velocities — undergo chronic transfusions to mitigate their risk. However, chronic transfusions are associated with severe adverse events, including iron overload.

Francoise Bernaudin , MD, of the referral center for sickle cell disease in the department of pediatrics at the Centre Hospitalier Intercommunal, in Creteil, France, and colleagues evaluated long-term follow-up data from 309 children with sickle cell anemia enrolled on the newborn-CHIC-Crétail-cohort and followed since birth. These patients had a least 1-year follow-up with TCD imaging.

Patients with normalized TCD velocities switched to hydroxyurea and were followed with trimestriel Doppler. These patients restarted transfusions if they reverted to abnormal velocities.

Patients underwent transplantation if they had a genoidentical donor.

The mean age of the cohort was 1.7 ± 0.6 years (range, 0.5-3.2 years) at the time of the first TCD imaging and 8.1 ± 4.5 years (range, 2-19 years) at their last TCD imaging.

Ninety-two children (29.8%) had a history of abnormal TCD imaging at the mean age of 3.7 ± 1.5 years (range, 1.3-8.3 years).

After a mean follow-up of 6.1 ± 3.6 years (range, 0.7-16 years), no strokes occurred after transfusion in this population.

Parents of one of the patients declined transfusions, and that patient was treated with hydroxyurea.

The other 91 patients were placed on chronic transfusion.

Seventy-six patients (83.5%) achieved normalized TCD velocities at a median age of 5.3 ± 1.9 years (range, 1.8-10.8 years), following a mean duration of chronic transfusion of 1.4 ± 1.3 years (range, 0.3-6.9 years).

Stenosis — which occurred in 27.5% of the children — appeared associated with risk for non-TCD normalization (HR = 2.6; 95% CI, 1.5-4).

Forty-five patients with normal velocities and no persistent stenosis switched to hydroxyurea. Median follow-up for this cohort was 3.4 years.

Reversion occurred in 13 patients (28.9%) at the mean age of 7.1 ± 1.6 years (range, 4.3-9.5 years). The reversion occurred within the first month in four (8.9%) of these patients.

A multivariate Cox regression analysis that included all baseline blood parameters showed that reticulocyte count significantly predicted reversion while on hydroxyurea (HR = 1.005 per 1x10⁹/L increase; 95% CI, 1.001-1.009). Additionally, baseline reticulocyte counts of 400x10⁹/L or greater were highly predictive of reversion on hydroxyurea (HR = 6.3; 95% CI, 1.8-21.7).

Twenty-four patients with a genoidentical donor underwent stem cell transplantation, all of whom were alive at last follow-up with no chronic graft-versus-host disease. All but one of these patients had normalized velocities at their last TCD imaging.

The researchers noted the lack of a control group — due to the longitudinal prospective observational nature of the study — may be a limitation to these findings, as efficacy and net benefit could not be measured.

“Discontinuation of chronic transfusion in patients with a history of abnormal velocities with switch to hydroxyurea can be safe in a subset of patients with normalized velocities and no stenosis, provided that the patients be reassessed with Doppler each trimester and transfusions reinitiated as soon as abnormal velocities return,” the researchers wrote. “However, transplantation with a genoidentical donor remains the only procedure allowing the safe cessation of transfusions in all patients. – by Anthony SanFilippo

Disclosure: The researchers report no relevant financial disclosures.