This session will feature new research into strategies for improving outcomes and reducing the treatment burden for children and adults with sickle cell disease (SCD) that could be practice changing. One study examines a new way to prevent stroke in children by administering hydroxyurea, a pill, instead of subjecting them to blood transfusions. Another study reports on outcomes from a large, long-term analysis of children with SCD who received stem cell transplant from a sibling. Finally, researchers will present promising data on a new oral agent that may safely and effectively target the underlying mechanisms of red blood cell sickling.
Russell E. Ware, et al.
3 TCD with Transfusions Changing to Hydroxyurea (TWiTCH): Hydroxyurea Therapy As an Alternative to Transfusions for Primary Stroke Prevention in Children with Sickle Cell Anemia.
Conclusion: In the multicenter Phase III TWiTCH trial, which treated children with SCA and abnormal TCD velocities but without severe MRA vasculopathy, hydroxyurea at MTD was non-inferior and possibly superior to chronic transfusions for maintaining TCD velocities. Serial phlebotomy effectively managed iron overload. Hydroxyurea may represent an effective alternative to indefinite transfusions for the prevention of primary stroke in this high risk population. SLIDES
Barbara Cappelli, et al.
541 Hematopoietic Stem Cell Transplantation from HLA Identical Sibling Forsickle Cell Disease an International Survey on Behalf of Eurocord-Monacord, EBMT Paediatric Disease Working Party and CIBMTR.
Conclusion: This large registry based international study shows that HLA identical sibling transplant is successful more than 90% of the patients with severe SCD with limited transplant related complications (rejection, GVHD). Strategies aimed at lowering graft failure and GVHD are desirable to further optimize the observed 3-year event-free survival. Importantly, these data should increase awareness to early referral to HSCT of patients with severe SCD. SLIDES
Claire Jane Hemmaway, et al.
542 GBT440, a Potent Anti-Sickling Hemoglobin Modifier Reduces Hemolysis, Improves Anemia and Nearly Eliminates Sickle Cells in Peripheral Blood of Patients with Sickle Cell Disease.
Conclusions: Single, oral, daily dosing with GBT440 was well tolerated across a wide dose range and demonstrated dose proportional and predictable PK and PD. GBT440 demonstrated proof of mechanism with a dose-dependent increase in hemoglobin oxygen affinity without causing tissue hypoxia. GBT440 demonstrated proof of concept in SCD patients with rapid reduction in RBC hemolysis and improved oxygen delivery to tissues as evidenced by reduced erythropoietin level, and a marked reduction in circulating sickle cells. These results support further clinical investigation of GBT440 as a potential disease-modifying therapy for SCD. SLIDES