Children born with immunodeficiencies may be able to look forward to an alternative treatment to chemotherapy to get the help they need from stem-cell transplants.

Researchers in the department of bone marrow transplanation at Great Ormond Street Children’s Hospital in London have found a regimen using antibodies instead of high-dose chemotherapy that may help even the sickest children.

Children with primary immunodeficiencies have genetic defects in their immune stystme that leave them susceptible to infections and other complications. However, stem-cell transplants can replace the defective immune system with one derived from the bone marrow of a healthy donor. Without a stem-cell transplant, many children may die.

To create space for the donor stem cells and prevent rejection, the
patient usually undergoes chemotherapy or radiotherapy or both which can cause severe liver or lung damage as well as hair loss and sickness. In addition, the chemoradiotherapy can cause problems with growth, puberty and infertility later in life.

In this study, rather than using high-dose chemotherapy, researchers used immune molecules made by white blood cells, called monoclonal antibodies. The method targeted molecules called CD45 and CD52 which are specific to bone marrow and blood cells. In this way, the monoclonal antibodies targeted only the immune cells that cause rejection and did not affect other body tissues.

Using this approach, the 16 children in the study who had primary immunodeficiencies and were too sick for a traditional stem-cell transplant, were able to avoid much of the toxicity caused by chemotherapy. Furthermore, the approach was well-tolerated by patients who were extremely sick at the time of the transplant.

The researchers reported no signs of sickness or hair loss among those who participated in the study and there was less damage to the liver and lungs. In addition, patients recovered faster than those who were given the standard treatment and almost all of the children are doing well and are expected to have few problems later in life.