Grant will allow researchers to study cancer that strikes young transplant recipients

Prediction and early detection of a high-risk form of childhood cancer are the goals of an ambitious new study led by scientists at Lucile Packard Children's Hospital and the School of Medicine.

The study, funded by a $6.9 million, five-year grant from the National Institutes of Health, targets a form of cancer that strikes children who have received solid organ transplants. Because they take immune-suppressing medications to keep their transplanted organs safe, these children are vulnerable to a cancer caused by an inappropriate immune-system response to a common virus.

The cancer, called post-transplant lymphoproliferative disorder, is a malignancy of the white blood cells. At present, doctors cannot tell which young organ recipients are likely to develop PTLD, and often the cancer cannot be detected until it causes clinical signs or symptoms. The cancer's mortality rate can be as high as 35 percent. About 150 children develop the cancer each year in the United States, and many more are at risk.

"We want to develop assays so that we can identify children who are at risk for PTLD before they even develop the disease," said Carlos Esquivel, MD, PhD, a liver transplant surgeon at Packard Children's who is the principal investigator of the new study.

The scientists will also investigate a possible PTLD marker that may allow them to find the cancer before it causes symptoms, said Esquivel, who is also a professor of surgery at the medical school. "With these tests, we might be able to modify the child's immunosuppression or take other preventive or early-treatment measures," he added.

"Our study is unique in that it is bringing to bear Stanford's incredible expertise in the basic sciences of immunology, virology and cancer all together to try to answer a critical clinical question that disproportionately affects children," said Daniel Bernstein, MD, a professor of pediatric cardiology who co-directs the study with Esquivel.

PTLD is caused by the Epstein-Barr virus. The virus is so common that most adults have been exposed to it. In healthy children and teenagers, the first exposure typically causes self-limiting illnesses, after which the virus goes into a dormant state in the person's immune cells.

In contrast, in an organ transplant recipient who has never had the virus, the immune cells that help control the body's response to it function poorly. The child's first exposure to the virus can lead to a malignant overgrowth of a specific type of white blood cell, B lymphocytes.

With the new grant, Stanford/Packard Children's researchers will examine two possible markers of PTLD. Olivia Martinez, PhD, research professor of surgery in multi-organ transplantation, has identified two mutant forms of the Epstein-Barr virus that appear only in transplant recipients; her team will verify whether children who have the mutated forms are at greater risk for developing PTLD.

A second project will be co-directed by Kenneth Weinberg, MD, professor of pediatric stem cell transplantation, and Scott Boyd, MD, PhD, assistant professor of pathology, who will study whether an early warning system for PTLD could be devised by looking for small numbers of abnormal B lymphocytes in a child's blood before detectable tumors develop. The study will include pediatric organ transplant recipients from Packard Children's, UCLA, the University of Texas-Southwestern, the University of Nebraska and the University of Miami.