Clinicians at St. Jude Children's Research Hospital have successfully demonstrated an improved technique for blood stem cell transplantations in children that shows promise for those most likely to fail standard treatment for leukemia.
The St. Jude technique allows blood stem cells to come from parents or unmatched adult siblings; and it avoids the aggressive, toxic treatments that usually must accompany the transplant. This allows the majority of patients with leukemia or non-cancerous blood disorders to receive a transplant, according to Gregory Hale, M.D., St. Jude Bone Marrow Transplantation Division interim chief. A report on this work appears in the prepublication edition of the British Journal of Haematology.
A clinical trial of this technique demonstrated that it accelerated recovery of the immune system in recipients and shortened the duration of immune deficiency during the early post-transplant period, reducing the risk of infections. The immune system recovery included not only T and B lymphocytes, the major cells genetically programmed to attack specific targets, but also natural killer cells, a critical first-response army of cells that acts as a quick-strike force against a wide variety of targets.
"The overall success of this procedure suggests it holds promise for children who are likely to fail standard treatment for leukemia because they have treatment-resistant disease and no matched donor," Hale said.
The key to the St. Jude strategy--reduced intensity conditioning regimen (RICR)--is that it avoids the total-body irradiation routinely used to kill the recipient's own stem cells to make way for the transplantation. RICR also avoids the use of anti-thymocyte globulin (ATG), a drug commonly used to suppress the remaining immune system of recipients in order to reduce the chance they will reject the transplanted blood stem cells. ATG often delays rebuilding of the immune system in transplant recipients and can lead to a virus-related lymphoma. The standard treatment, called myeloablative conditioning regimen (MCR) uses total body irradiation, ATG and other drugs to eradicate the patient's own blood stem cells and suppress the remaining immune system to prevent rejection of the transplanted blood stem cells.
The underlying technique that permitted the team to eliminate total body irradiation and ATG was the use of haploidentical hematopoietic stem cell transplantation (HaploHSCT) for children, which was previously pioneered by St. Jude investigators. Before this technique, only matched transplants from a genetic twin or from a matched, unrelated donor could be used, since unmatched donations led to unacceptably high rates of severe graft-versus-host disease (GVHD).
However, the St. Jude technique treats partially matched donor blood stem cells to remove the aggressive immune system cells called T lymphocytes that normally cause GVHD. GVHD occurs when donor immune cells respond to the recipient as foreign and launch an attack on the body.
An additional advantage of this new treatment is that donor immune cells are likely to attack the leukemic cells remaining in the recipient, a reaction called a graft-versus-tumor response, according to the researchers.