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$6.9 million grant for Stanford/Packard Children’s study of pediatric cancer that strikes organ transplant recipients

PALO ALTO, Calif. --

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 Stanford University 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 U.S., 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 professor of surgery in multi-organ transplantation at the School of Medicine. “With these tests, we might be able to modify the child’s immunosuppression or take other preventive or early-treatment measures,” he said.

“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 Stanford/Packard Children’s pediatric cardiologist Daniel Bernstein, MD, who co-directs the project with Esquivel. Packard Children’s, a top pediatric organ transplantation center, will serve as an important venue for the research, added Bernstein, who is professor of pediatric cardiology.

PTLD is caused by the Epstein-Barr virus. The virus is so common that most adults have been exposed to it. In healthy young children, the first exposure typically causes a short, cold-like sickness; healthy teenagers exposed for the first time get infectious mononucleosis. After these illnesses subside, the virus normally 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. The risk of PTLD varies depending on the type of organ transplant a child has received, since different organs require different degrees of immune suppression, and with age, since young children are less likely to have been infected with the virus before transplant. (Adult organ recipients can also get PTLD, but since most have had the virus before transplant, their risk is much lower.) The risk of PTLD is highest for children who receive intestinal or heart transplants; of these groups, 30 and 10 percent of organ recipients develop the cancer, respectively.

The Stanford/Packard Children’s research team will examine two possible markers of PTLD. Olivia Martinez, PhD, research professor of surgery in multi-organ transplantation, will lead one project. Martinez 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. Other scientists working on this project include Sheri Krams, PhD, associate research professor of surgery in multi-organ transplantation and Stephen Quake, Ph.D., professor of bioengineering.

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 Stanford/Packard Children’s clinical investigators involved in the project include Clare Twist, MD, associate professor of pediatric hematology and oncology; William Berquist, MD, professor of pediatric gastroenterology and specialist in pediatric liver transplantation; Ricardo Castillo, MD, associate professor of pediatric gastroenterology and specialist in pediatric intestinal transplantation; David Rosenthal, MD, professor of pediatric cardiology and specialist in pediatric heart transplantation; and John Higgins, MD, associate professor of pathology.

The study will include pediatric organ transplant recipients from Packard Children’s and four other study sites: the University of California-Los Angeles, the University of Texas-Southwestern, the University of Nebraska and the University of Miami. With the project, Stanford and Packard Children’s will join the Clinical Trials on Transplantation in Children consortium, a prestigious research group sponsored by the NIH and the National Institute of Allergy and Infectious Diseases.

About Stanford University School of Medicine
The Stanford University School of Medicine consistently ranks among the nation’s top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children’s Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.



About Stanford Children’s Health and Lucile Packard Children’s Hospital Stanford
Stanford Children’s Health, with Lucile Packard Children’s Hospital Stanford at its core, is an internationally recognized leader in world-class, nurturing care and extraordinary outcomes in every pediatric and obstetric specialty from the routine to rare, for every child and pregnant woman. Together with our Stanford Medicine physicians, nurses, and staff, we deliver this innovative care and research through partnerships, collaborations, outreach, specialty clinics and primary care practices at more than 100 locations in the U.S. western region. As a non-profit, we are committed to supporting our community – from caring for uninsured or underinsured kids, homeless teens and pregnant moms, to helping re-establish school nurse positions in local schools. Learn more about our full range of preeminent programs and network of care at stanfordchildrens.org, and on our Healthier, Happy Lives blog. Join us on Facebook, Twitter, LinkedIn, and YouTube.


Lucile Packard Children’s Hospital Stanford
is the heart of Stanford Children’s Health, and is one of the nation’s top hospitals for the care of children and expectant mothers. For a decade, we have received the highest specialty rankings of any Northern California children’s hospital, according to U.S. News & World Report’s 2014-15 Best Children’s Hospitals survey, and are the only hospital in Northern California to receive the national 2013 Leapfrog Group Top Children’s Hospital award for quality and patient care safety. Discover more at stanfordchildrens.org.