Stem cell transplantation in sickle cell disease

Stem cell transplantation remains the only curative therapy for Sickle Cell Disease (SCD) and near 200 SCD patients have been transplanted worldwide. The French transplant experience includes 70 severe SCD patients (2.2 to 22 years old) transplanted since 1988, using myeloablative conditioning regimen and genoidentical sibling donor. Median follow-up was 3.8 years and the Kaplan-Meier estimates of survival and event free survival (EFS) were 91.4% and 84.1%. The rate of rejections was significantly reduced (23.5% to 2%) by the addition of anti-thymoglobulin (ATG) and dose adjustment of busulfan. Transplant-related mortality (9%) was principally GVH related and was reduced over the course of the study (no deaths among the last 31 patients). Moreover, GVHD was significantly decreased in cord blood transplants (n=7). In < 15 years old patients, conditioned with ATG, EFS was 91%. The only CR-related toxicity was a gonadal insufficiency in girls encouraging to offer pretransplant ovarian cryopreservation. No veno-occlusive disease was observed. Among patients with a stroke history (n=27), the risk of recurrence was only of 6.7% with a median follow-up of 5.1 years. Splenic function and SCD-related osteonecrosis were improved. These results encourage sibling cord blood cryopreservation and to propose earlier SCT for high risk patients using myeloablative CR in order to obtain a definitive cure.