Michael Pulsipher, M.D., of the Children’s Center for Cancer and Blood Diseases at Children’s Hospital Los Angeles, along with co-principal investigator, Sung-Yun Pai, M.D., of Boston Children’s Hospital, has been awarded nearly $9 million from the National Institute of Allergy and Infectious Diseases of the NIH to study a new treatment approach for babies born with severe combined immunodeficiency (SCID), which prevents the immune system from functioning normally. In a multi-site study, investigators plan to determine the lowest dose of chemotherapy needed for babies with SCID undergoing bone marrow transplant—the standard treatment for SCID. The goal is to restore the immune system safely and effectively with less toxicity than the higher dose regimens currently in use.

Severe combined immunodeficiency (SCID) is a rare genetic disorder characterized by disturbed development of the T cells and B cells resulting in an immune system that is so highly compromised that it is considered nonexistent. Children with SCID, also known as the bubble boy syndrome, lack the ability to fight off even the most benign infections.

Babies with SCID usually die of infection before their second birthday unless they have a bone marrow transplant (BMT). The transplanted cells are injected into the blood stream where they become healthy white blood cells that serve to restore immune function and rebuild the patient’s immune system.

The objective of the new study is to complete the first ever randomized trial in this challenging rare disease. Infants who are determined to have SCID by newborn screening will be randomized to receive a low- or moderate-dose of busulfan—a type of chemotherapy that acts to suppress the immune system in preparation for the transplant.

The investigators propose that BMT can be performed successfully in SCID patients without the higher dose of busulfan typically used, due to the patients’ lack of functional T cells. Because of their already reduced immune system, the investigators theorize that giving a lower dosage of busulfan will be as effective and safer for patients.

“Our goal is to decrease the possible long-term effects from chemotherapy by determining the lowest doses needed to insure T and B-cell function in these infants, restoring normal immune systems that can last throughout their lives,” said Pulsipher, who is chair of the Pediatric Blood and Marrow Transplantation Consortium (PBMTC), section head of BMT at CHLA and professor of pediatrics at the Keck School of Medicine of USC.

The study was organized as a joint project between the PBMTC and the Primary Immune Deficiency Treatment Consortium (PIDTC), a group of over 40 centers in North America dedicated to improving therapy for children with immune deficiencies. As the primary recipient of the NIH award, CHLA will act as coordinating center for the study, which will involve 50 centers in the US and Canada. In addition to CHLA and Boston Children’s Hospital, other institutions receiving funding to carry out the study include the Medical College of Wisconsin, University of California, San Francisco, University of Pittsburgh, the CHU Sainte-Justine Research Center of the University of Montreal and the National Marrow Donor Program headquartered in Minneapolis.