UCLA

Children with sickle cell disease (SCD) are at high-risk of progressive, chronic pulmonary and cardiac dysfunction. In this prospective multicenter Phase II trial of myeloimmunoablative conditioning followed by haploidentical stem cell transplantation in children with high-risk SCD, 19 patients, 2.0-21.0 years of age, were enrolled with one or more of the following: history of (1) overt stroke; (2) silent stroke; (3) elevated transcranial Doppler velocity; (4) multiple vaso-occlusive crises; and/or (5) two or more acute chest syndromes and received haploidentical transplants from 18 parental donors. Cardiac and pulmonary centralized cores were established. Pulmonary function results were expressed as percent of the median of healthy reference cohorts, matched for age, sex, height and race. At 2 years, pulmonary functions including forced expiratory volume (FEV), FEV₁/ forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity of lung for carbon monoxide (DLCO) were stable to improved compared to baseline values. Importantly, specific airway conductance was significantly improved at 2 years (p < 0.004). Left ventricular systolic function (fractional shortening) and tricuspid regurgitant velocity were stable at 2 years. These results demonstrate that haploidentical stem cell transplantation can stabilize or improve cardiopulmonary function in patients with SCD.