A new technique for blood stem cell transplantation avoids whole-body irradiation and improves recovery of immune system function in children with leukemia, according to an article in the November issue of the British Journal of Haematology.

Because the new technique allows blood stem cells to be donated by parents or unmatched adult siblings and avoids aggressive pre-transplantation treatment, it allows the majority of patients with leukemia or non-cancerous blood disorders to undergo transplantation, according to Gregory Hale, MD, of St. Jude Children’s Research Hospital, Memphis, Tennessee, USA, and lead author.

A clinical trial demonstrated that the new technique accelerated recovery of immune system function in recipients during the early post-transplant period, reducing the risk of infections. The immune system recovery included not only T and B lymphocytes, but also natural killer cells, critical first-response cells.
“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 strategy, called reduced intensity conditioning regimen (RICR), avoids total-body irradiation and use of anti-thymocyte globulin (ATG). 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 and 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.

Key to the new technique’s success is use of haplo-identical hematopoietic stem cell transplantation (HaploHSCT), which was pioneered by St. Jude investigators. Before this technique, only matched transplants from a genetic twin or from a matched, unrelated donor could be used because unmatched donations led to unacceptably high rates of severe graft-versus-host disease (GVHD).

The new technique treats partially matched donor blood stem cells to remove T lymphocytes, which normally cause GVHD. An additional advantage is that donor immune cells are likely to attack remaining leukemic cells, an example of graft-versus-tumor response.

During a 12-month follow-up after transplantation, the team compared results of its modified transplantation technique with results from a group of patients with refractory blood cancers who were treated with standard technique.

Of 22 children who underwent the reduced intensity regimen, 91 percent achieved full donor chimerism; that is, the recipient’s body built a blood system that was identical to that of the donor. Among children who received standard therapy, 92 percent achieved full donor chimerism.

Acute graft-versus-host disease developed in 12 patients in the reduced intensity group and 2 in the standard group; 5 reduced-intensity patients developed chronic disease, but none had died by one year as a result.

The team also reported that reduced-intensity patients had a rapid recovery of immune system cells during the first four months after transplantation compared with patients who had undergone standard transplantation. This rapid recovery of the immune system reduced occurrence of viral infection, the researchers reported.

“Many viruses exist in the body in an inactive state, even after a person clears an initial infection,” Hale explained. “A healthy immune system keeps those viruses in check, but after a transplant, the patient’s immune system is rebuilding and not capable of mounting a strong defense. That leaves the patient vulnerable to developing hepatitis, gastroenteritis, encephalitis or other diseases that can be fatal.”

Viral infections can also cause graft failure or prolong the need for transfusions to supplement red blood cells or platelets, he added. Viral infections can further weaken the immune system of transplant recipients, leaving them vulnerable to fungal infections. Moreover, the drugs used to treat those viral infections and reactivation of old infections can cause low blood counts and kidney damage.