First Prospective Randomized Study Demonstrates Safety, Efficacy of Transfusion Therapy in Adults With Sickle Cell Disease

ORLANDO, Fla.Transfusion therapy in adults with sickle cell disease (SCD) is safe and improves or stabilizes critical laboratory markers, decreases serious sickle cell anemia-related adverse events, and decreases hospitalizations, preliminary data from the first prospective randomized study of the safety and efficacy of transfusion therapy in adults with SCD has found.

Most adults with SCD have received transfusion therapy. However, prospective studies evaluating the efficacy of transfusions in preventing complications of the disease are lacking, Elliott Vichinsky, MD, of Children's Hospital & Research Center Oakland, Oakland, Calif., and colleagues reported.

These results delineate the secondary goal of the study, which was to evaluate the benefit of chronic transfusion on frequency and severity of acute sickle cell events. The primary goal of the phase 2 National Heart, Lung and Blood Institute Comprehensive Sickle Cell Centers (CSCC) Study of Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adult Patients with Sickle Cell Disease, a randomized trial of chronic transfusion vs standard of care in patients with abnormal neurocognitive function, is being conducted to determine the safety and benefits of transfusion therapy on neurocognitive function. When completed, the potential benefits of transfusion therapy in SCD morbidity—including neurocognitive function—will be reported, the investigators noted in a poster presentation at the 52nd American Society of Hematology Annual Meeting and Exposition.

Study eligibility included a normal neurological exam, a WAIS III PIQ score ≤90, hemoglobin (Hb) ≤9 g/dL, hemoglobin SS electrophoresis, and age 21-55 years. Patients were randomly assigned to receive either standard care or transfusions. The goal of transfusion was to maintain an increase in Hb of 2 g/dL over baseline with matched red cells for D, C/c, E/e, and Kell antigens. Simple transfusions occurred at approximately 4-week intervals. Study design did not include chelation therapy. Serial clinical and laboratory evaluations were conducted with central analysis of all clinical and transfusion events and complications. In the transfusion arm, laboratory testing included quantitative Hb S/A, Hb concentration, ferritin levels, and red cell antibody screening. A full hematology/chemistry panel was performed for all subjects at baseline, study midpoint, and study completion.

A total of 34 patients were enrolled, 18 in the transfusion arm and 16 in the standard care arm. Baseline characteristics were similar: Hb 7.8 vs 8.0 g/dL; hematocrit 22.6% vs 23.1%; Hb F 10.5% vs 12.5% for the transfusion and standard care arms, respectively. In the transfusion arm, 35% of patients had a history of acute chest syndrome and 30% were on hydroxyurea, vs 38% and 50% in the standard care arm. Patients in the transfusion arm received an average of 6.7 transfusions (13.6 units per patient), and patients in the standard care arm received an average of 6 transfusions (2.4 units per patient), with no one requiring an acute transfusion.

Transfusion therapy was found to improve the average hematologic status of patients: hemoglobin S% decreased 46.1% (±22.8); Hb and hematocrit increased 1.8% (±1.6). In the transfusion arm, serum ferritin increased 1179 (±839); this outcome is to be expected, since chelation is not part of the transfusion protocol.

Patients in the standard care arm reported more adverse events: 66 (4.13 per person) compared with 23 (1.15 per person) in the transfusion arm. Hospitalizations were also greater: 22 in the standard care arm vs 7 in the transfusion arm. Vaso-occlusive events totaled 5 (0.25 per person) in the standard care arm and 21 (1.31 per person) in the transfusion arm; acute pulmonary events occurred in 3 patients in the standard care arm vs none in the transfusion arm.