Pediatric patients with severe sickle cell disease have new reason to hope that their disease can be cured with new breakthroughs in myeoloablative allogeneic stem cell transplants. Researchers from France found an 85 per cent disease-free survival rate in children using myeloablative stem cell transplant and sibling donors, according to a study. Myeloablative allogeneic stem cell transplants involve the temporary destruction of a patient's bone marrow to allow the transplantation of donor cells.

The study looked at 69 children with severe sickle cell disease with a median age of 8.9 years. Two conditioning regimens were tested prior to transplantation: The first twelve cases (n=12) used busulfan and cyclophosphamide (BU+CY) and the subsequent cases used busulfan, cyclophosphamide, and rabbit anti-thymocyte globulin (ATG). Stem cell transplant was performed with bone marrow (n=60), cord blood (n=7), cord blood and bone marrow (n=1), and peripheral blood stem cells (n=1).

Engraftment was successful in all but one case. Before the addition of ATG, investigators found mixed chimerism (two genetically distinct types of cells) followed by rejection in four out of 12 patients. One case of aplasia (defective development or congenital absence of an organ) required a second successful bone marrow transplant, and three cases of progressive autologous reconstitution were observed. In contrast, no rejection was observed in the group whose conditioning regimen included ATG.

"We are greatly encouraged by our findings," said Francoise Bernaudin, lead investigator, Saint Louis Hospital, Paris and Creteil, France. "The early identification of patients at high risk for sickle cell disease-related complications coupled with the conditioning regimen and use of sibling donors shows tremendous promise. The side effects are minimal and the fact that we can use the word 'cure' suggests significant progress against this terrible disease."

Of the 69 cases, there were six deaths: one from sepsis during aplasia, one from hemorrhagic cerebrovascular accident (stroke), and four due to graft-versus-host complications. Follow-up (median 36 months), using Kaplan-Meier estimates, showed that survival and event-free survival were 91.3 per cent and 84.1 per cent respectively. Disease free survival was 90 per cent in children younger than 15 years and having received ATG. No occurrence of stroke was observed in 27 out of 29 patients after a median follow-up of 62 months and splenic function and sickle cell disease-related osteonecrosis (bone death resulting from poor blood supply to an area of bone) were improved.

"This study offers such hope to those with sickle cell disease," said Robert I. Handin, president of the American Society of Hematology. "It demonstrates an unprecedented cure rate for children and at the same time does not produce greater toxicity or serious complications. This is the kind of science that makes our meeting sing."

Sickle cell disease is an inherited chronic blood disorder that affects red blood cells. People with sickle cell disease have red blood cells that contain mostly hemoglobin S, an abnormal type of hemoglobin that sometimes causes these cells to become sickle-shaped (crescent-shaped), resulting in difficulty passing through small blood vessels.