Two Children’s Hospital physicians are blazing new trails in childhood cancer research and giving renewed hope to families across the country.

The first pediatric Dream Team of researchers, led by John M. Maris, MD, director of CHOP’s Center for Childhood Cancer Research (CCCR), will build on pioneering results realized by CCCR’s Director of Translational Research Stephan Grupp, MD, PhD, to treat childhood leukemia. These two researchers are actively involved in new classes of treatments to improve children’s survival and quality of life in the 21st century.

Dr. Grupp recently achieved groundbreaking results using an innovative T cell therapy to treat a patient with an aggressive form of childhood leukemia called acute lymphoblastic leukemia (ALL). The most common form of childhood leukemia and the most common childhood cancer, ALL is highly treatable for approximately 85 percent of cases. But the remaining 15 percent of such cases resist standard therapy.

Dr. Grupp’s work made all the difference for 7-year-old Emma Whitehead, whose prospects were bleak when her cancer relapsed after she received the conventional treatment for ALL. With few other viable options, Dr. Grupp turned to an experimental therapy using bioengineered T cells that were designed to multiply rapidly and destroy leukemia cells. In other words, Dr. Grupp reprogrammed Emma’s own immune cells to attack the ALL cells.

As the workhorses of the immune system, T cells recognize and attack invading disease cells. However, cancer cells fly under the radar of immune surveillance, evading detection by T cells. In what’s known as CTL019 therapy, CAR T cells (chimeric antigen receptor T cells) are engineered to specifically target B cells, which become cancerous in certain leukemias like ALL, as well as types of lymphoma, another cancer of the immune cells.

Amazingly, just three weeks after the treatment, Emma’s doctors found no traces of cancer. A year later, Emma remains healthy and cancer-free.

Such dramatic results bode well for successfully treating resistant cases of childhood ALL and possibly other types of cancer as well. “These engineered T cells have proven to be active in B cell leukemia in adults,” said Dr. Grupp. “We are excited to see that the CTL019 approach may be effective in untreatable cases of pediatric ALL as well. Our hope is that these results will lead to widely available treatments for high-risk B cell leukemia and lymphoma, and perhaps other cancers in the future.”

Emma received the therapy as part of a research clinical trial conducted by investigators at CHOP and the Perelman School of Medicine at the University of Pennsylvania. Recently, Dr. Grupp and the CHOP/Penn team have reported an 82 percent complete response rate in a study that has included 20 children — including Emma and one other pediatric patient — and 5 adults with ALL. A major update on this study will be presented at the upcoming American Society of Hematology annual meeting in December.

Emma was a guest of honor at the announcement of the first pediatric “Dream Team” of cancer researcher solely focused on creating new treatments for the most challenging childhood cancers. CHOP’s Dr. Maris was chosen to co-lead the Dream Team, which was announced at the American Association for Cancer Research annual meeting in Washington, D.C. Crystal L. Mackall, MD, chief of the Pediatric Oncology Branch of the National Cancer Institute, is the Dream Team’s other co-leader.

“The motivation for the creation of this collaborative research project is the realization that completely new strategies are needed if we are to have curative therapies for all childhood cancers,” said Dr. Maris. “Our team hopes to rapidly develop more precise and effective treatments based on the unique characteristics of each child’s tumor, here focusing on the genetic changes that make the cancer cells different from the rest of the child’s body.”

The Dream Team will receive $14.5 million in funding over 4 years, provided by Stand Up to Cancer (SUC2) and St. Baldrick’s Foundation. The research project, called “Immunogenomics to Create New Therapies for High-Risk Childhood Cancers,” melds two disciplines that have historically functioned independently: immunotherapeutics and genomics. The goal of the project is to rapidly translate promising basic research into transformative, targeted treatments that will improve cure rates in children’s cancer.

Recent research in genomics has shown that pediatric cancers are fundamentally different from adult cancers, explained Dr. Maris. Children’s cancers are less likely to arise due to recurring mutations that can be countered with small molecule drugs. Instead, the Dream Team will exploit the unique feature of molecules on cell surfaces of childhood cancer cells that are not present on normal cells, and offer targets for treatments employing bioengineered agents working through the immune system.

“The success of the program will ultimately be judged by the number of lives saved through our efforts,” said Dr. Maris.

The Dream Team will take on the four most deadly pediatric cancers: malignant brain tumors, high-risk leukemias (such as the type of ALL that Emma had), neuroblastomas (which affect the peripheral nervous system), and sarcomas (other tumors of bone and other tissue). Dr. Grupp and Tom Curran, PhD, FRS, deputy director of the CHOP Research Institute, will lead the CHOP-based research efforts.

Research Institute investigators are often more than just leaders in their fields. Seemingly tireless, many CHOP researchers regularly use their expertise to help improve public policies and legislation related to children’s health, while also advancing pediatric medical research. By contributing to interdisciplinary programs and government panels, Children’s Hospital researchers “lead from the front,” advancing changes that will improve the health and welfare of children now and in the future.

In a recent significant example of this, co-director of The Children’s Hospital of Philadelphia’s PolicyLab David Rubin, MD, MSCE, was recently appointed to a government commission tasked with working to end child abuse and neglect-related deaths. Dr. Rubin is one of twelve experts from a variety of fields to be named to the Commission to Eliminate Child Abuse and Neglect Fatalities, and one of just six appointed by President Obama. Notably, Dr. Rubin is the only health care provider appointed to the commission.

The commission was established as part of the Protect Our Kids Act of 2012. By creating a commission of child welfare experts, pediatricians, and jurists, the Protect Our Kids Act seeks to “develop a national strategy and recommendations for reducing fatalities resulting from child abuse and neglect,” according to the law’s text. A rare example of bipartisan accord, the House of Representatives voted 330-77 in favor of the act before it quickly proceeded through the Senate. President Obama signed the act into law on January 14, 2013.

The Protect Our Kids Act was inspired in part by a 2011 Government Accountability Office (GAO) report on child fatalities from abuse and neglect. According to the National Child Abuse and Neglect Data System (NCANDS) — a voluntary reporting system that collects data from all 50 states as well as the District of Columbia and Puerto Rico — in 2009 there were 1,770 child deaths due to abuse and neglect.

However, the true number of child deaths that year was likely higher, the GAO report states, both because the NCANDS is a voluntary data-collection system, and because “nearly half of states report to NCANDS data only on children who were already known to” child protective services (CPS). However, not all children who die from abuse or neglect are brought to the attention of CPS, the report states.

“As a society, we should be doing everything in our collective power to end child deaths and near deaths from maltreatment, and the collection and reporting of comprehensive data on these tragic situations is an important step toward that goal,” the GAO report concluded.

As a first step in preventing child deaths from mistreatment, the Protect Our Kids Act charges the Commission to Eliminate Child Abuse and Neglect Fatalities with conducting a survey of child welfare and protection services, in order to determine the effectiveness of existing policies and services. The commission, which will offer education opportunities to graduate students, will also examine barriers to improving child welfare, child abuse and neglect trends, and methods of improving data collection.

Based on its work, the commission will “develop recommendations to reduce fatalities from child abuse and neglect,” as well as developing data tracking guidelines. The commission is due to submit a report to the President and Congress on its work within two years.

Six members of the commission were appointed directly by President Obama, while three were appointed by the House of Representatives and three by the Senate. In addition to Dr. Rubin, commission members include Theresa Martha Covington, MPH, director of the National Center for the Review and Prevention of Child Deaths, Marilyn Bruguier Zimmerman, MSW, director of the National Native Children’s Trauma Center, and Susan Dreyfus, president and CEO of the Alliance for Children and Families. The Commission will be chaired by David Sanders, PhD, executive vice president of Casey Family Programs.

Along with current co-director Kathleen Noonan, JD, in 2008 Dr. Rubin founded PolicyLab, which works to develop evidence-based solutions for the most challenging health-related issues affecting children. In addition to his role at PolicyLab, Dr. Rubin is an associate professor of Pediatrics as the Perelman School of Medicine at the University of Pennsylvania, a senior fellow at the Leonard Davis Institute of Health Economics, and an associate program director of the Robert Wood Johnson Clinical Scholars Program at the University of Pennsylvania.

“As a pediatrician in Philadelphia, I see the toll that stress has on children and families,” Dr. Rubin said. “I am honored to have the opportunity to serve this commission and hope to bring my experiences serving children and families to think preventatively at the system level about what can be done to avoid unnecessary childhood injuries and fatalities.”

The CHOP Research Institute has joined a prominent network of hospitals and research bodies to translate genetic data into improved care that will benefit both current patients and future generations. The network is defining the future by using genetic information and electronic medical records to identify the genetic contributions to disease, with the overall goal of giving health care providers the tools to apply genomic knowledge to patient care.

CHOP’s Center for Applied Genomics (CAG) was recently awarded approximately $2.5 million over three years to mine electronic medical record data for future clinical use as part of the ongoing Electronic Medical Records and Genomics (eMERGE) Network. Hakon Hakonarson, MD, PhD, the director of CAG, serves as the principal investigator of the project and leads the network’s pediatric-centered efforts.

Being a part of the eMERGE network will “elevate the important information that genomic information delivers,” noted Dr. Hakonarson.

CAG’s inclusion in eMERGE is especially significant because it currently has the largest pediatric biorepository — comprising more than 40,000 children — and genome-wide association study (GWAS) genotyping facility in the world. CHOP is one of only three pediatric sites selected to take part in eMERGE, now in its second phase, and one of only 10 sites included overall. So in addition to being selected to join eMERGE Phase II, CAG is taking on the role of pediatric leader in the network.

Further, CAG’s participation will help advance the study of minority genetics because its biorepository includes a large minority population. This is an important contribution because only modest numbers of African-American patients have been included in GWAS to date. Approximately 38 percent of the subjects in CAG’s biorepository are African American, 6 percent Hispanic, and 4 percent are Asian.

Dr. Hakonarson and his team plan to use patients’ electronic medical records (EMRs) to mine “disease phenotypes and environmental exposure data in over 40 phenotypes” in order to establish a database for future clinical use. They will work to enable future sharing of genetic and genomic data with patients and establish guidelines for CAG’s biorepository and databases. In doing so, Dr. Hakonarson hopes to generate informed consent procedures that will foster clinical use of genomic data in concert with other eMERGE members.

CAG also plans to use this data to determine pharmacogenetic response profiles, working to determine biomarkers to inform clinical care. While the initial eMERGE funding will largely support disease susceptibility studies, Dr. Hakonarson also hopes to extend his group’s pharmacogenetic research through additional grants.

Funded and organized by the National Human Genome Research Institute (NHGRI), the eMERGE initiative is a consortium of U.S. medical institutions brought together to “develop, disseminate, and apply approaches to research that combine DNA biorepositories with electronic medical record (EMR) systems, for large-scale, high-throughput genetic research,” according to NHGRI. In addition to including an expanded number of institutions, a key goal of eMERGE Phase II is to explore ways to best incorporate genetic information into EMR data so it can be used in a clinical setting.

Audrey Rose Oberio made history just by being born. Audrey, whose birth marked the Hospital’s 1,000th fetal surgery patient, was born to Jackie and Gideon Oberio of Maryland.

CHOP’s Center for Fetal Diagnosis and Treatment gave the Oberio family new hope and optimism for their baby’s future. The Center’s internationally renowned specialists treat the full range of fetal anomalies through highly complex surgical interventions to repair birth defects in the womb, changing outcomes for many children before they are even born.

The Center leads the way in fetal surgeries around the world. Approximately 4,000 fetal surgeries have been conducted worldwide, which means a quarter of them have been performed at CHOP, the largest number of any hospital in the world. The Center is firmly established at the forefront in providing and advancing fetal therapy, widely recognized as one of the most promising fields in pediatric medicine.

When Jackie Oberio was 19 weeks pregnant, the couple learned their unborn daughter had myelomeningocele, the most severe form of spina bifida, a condition in which part of the developing spine fails to close properly. With conventional postnatal surgery, myelomeningocele can still result in lifelong disabilities, including paralysis, bladder and bowel problems, and cognitive impairments.

After talking to local specialists and doing online research, the Oberios discovered that the Center for Fetal Diagnosis and Treatment pioneered a surgical procedure to repair spina bifida before birth. The Center’s team of physicians found that addressing spina bifida by operating on the baby in the womb, months before birth, could reduce the need to divert fluid from the brain, improve neurologic function, and increase the likelihood that a child would be able to walk independently.


When she was born post-surgery, Audrey Rose weighed 5 pounds, 8 ounces, and had nothing more than a scar where her doctors had operated.

“Although birth defects remain the leading cause of infant mortality in the United States, we have been able to develop and share innovations that help advance treatment for these defects, relying on tools, techniques and experience not available 30 years ago,” said N. Scott Adzick, MD, the Medical Director of the Center for Fetal Diagnosis and Treatment at CHOP, where he is also Surgeon-in-Chief.

Established by Dr. Adzick in 1995, the Center is now the largest and most comprehensive fetal program in the world, having welcomed nearly 15,000 expectant mothers from all 50 states and more than 50 countries. Each week at CHOP, highly sophisticated surgical teams repair spina bifida and other birth defects in the womb, place fetal shunts to treat life-threatening congenital conditions, or perform minimally invasive procedures in the mother’s uterus to treat complications in fetal twins. The Center staff also manages pregnancies complicated by birth defects, in which newborns need immediate specialized medical care or surgery after delivery.

In 2011, Dr. Adzick and his team published the results of more than two decades of research in the New England Journal of Medicine that showed fetal surgery can significantly improve the outcomes for children diagnosed in utero with spina bifida. Their study demonstrated that two and a half years after fetal surgery children with spina bifida were better able to walk when compared to children who received surgery shortly after birth, and patients who received fetal surgery scored better on tests of motor function.

“It’s very gratifying to take this idea forward over 30 years, starting with a concept and now offering hope — to families, mothers, and the children themselves,” said Dr. Adzick.

Alternative medicine, including dietary supplements and acupuncture, has become increasingly popular with many people. However Paul Offit, MD, isn’t one of them, and isn’t afraid to say so.

Dr. Offit is a leader in the medical community’s ongoing crusade against misinformation for his willingness to speak his mind, question popular (and at times ill-informed) wisdom, and defend science against its detractors. He is the chief of CHOP’s Division of Infectious Diseases and directs CHOP’s Vaccine Education Center. Dr. Offit is also a co-creator of the rotavirus vaccine Rotateq.

In a move sure to earn him some new critics, Dr. Offit recently published a new book, Do You Believe in Magic?: The Sense and Nonsense of Alternative Medicine. The book has received a great deal of attention from the media, including NBC News and CBS This Morning.

In his latest book, Dr. Offit examines the science and science fiction behind alternative therapies such as megavitamins and alternative treatments including coffee enemas and laetrile, a chemically modified form of amygdalin, a naturally-occurring substance found mainly in the pits of apricots and peaches, used to prevent and treat cancer.

Dr. Offit acknowledges in the book that people often turn to alternative treatments after becoming disillusioned with conventional medicine. However, while “conventional therapies can be disappointing, alternative therapies shouldn’t be given a free pass,” he says.

In fact, alternative medicine “can be quite harmful,” Dr. Offit points out in the book. “Chiropractic manipulations have torn arteries, causing permanent paralysis; acupuncture needles have caused serious viral infections or ended up in lungs, livers, or hearts; dietary supplements have caused bleeding, psychosis, liver dysfunction, heart arrhythmias, seizures, and brain swelling; and some megavitamins have been found to actually increase the risk of cancer,” he writes.

Conventional and alternative therapies should “be held to the same high standard of proof,” he notes in Do You Believe in Magic? For example, because megavitamins and other supplements are not regulated by the U.S. Food and Drug Administration, “consumers don’t know that taking megavitamins could increase their risk of cancer and heart disease and shorten their lives,” Dr. Offit writes.

“The truth is, there’s no such thing as conventional or alternative or complementary or integrative of holistic medicine. There’s only medicine that works and medicine that doesn’t,” he says in the book.

No stranger to controversy, hate mail, and even death threats, Dr. Offit’s previous books include Deadly Choices, about the anti-vaccine movement, and Autism’s False Prophets, about the now-discredited connection between vaccines and autism.

As one of the premier pediatric research institutions in the country, The Children’s Hospital of Philadelphia Research Institute has long been committed to training the next generation of pediatric researchers and clinicians. The Institute offers education programs at all levels, from those geared to undergraduates to opportunities for physician fellows.

During fiscal 2013, the Research Institute received funding to support training programs in a wide variety of disciplines. Programs in pharmacology, hematology, genetics, cardiology, oncology, endocrinology, and neonatology offered trainees the chance to gain hands-on experience and exposure to advanced scientific training and research techniques.

For example, the Neurodevelopmental Disabilities Training Program (NDTP) was established as a joint initiative of Children’s Hospital and the University of Pennsylvania in 1998, and is led by Children’s Hospital neuroscientist Michael Robinson, PhD. During fiscal 2013, the NDTP received an additional five years of funding totaling more than $1.7 million from the NIH’s National Institute of Neurological Disorders and Stroke.

Neurodevelopmental “disorders have diverse genetic and environmental causes, but they share many co-morbidities,” said Dr. Robinson. “Therefore the rationale was to bring together researchers from diverse training backgrounds and scientific expertise to both advance interdisciplinary training and encourage collaboration.”

The NDTP pairs trainees with faculty mentors, who provide advanced research training designed to help the trainees achieve their career goals. In addition to working closely with a mentor, NDTP trainees attend lectures and seminars, participate in clinical practica, and develop skills like grant writing. Trainees who have taken part in the program come from a variety of disciplines, including neurology and neuroscience, physics, and clinical psychology. Of the 26 trainees who have completed training, 13 have taken faculty positions at prestigious academic institutions across the country.

“It is gratifying to support such a talented group of individuals. Like a parent, I’m proud of the accomplishments of these trainees.” Dr. Robinson noted.

Several of the Research Institute’s Centers of Emphasis also offer their own training programs. The Center for Childhood Cancer Research, for example, offers post-doctoral trainees opportunities to participate in fellowships and research training. And the Center for Injury Research and Prevention (CIRP) has long been focused on training, with programs for both graduate and undergraduate researchers.

The Center offers programs in four scientific disciplines: behavioral science, epidemiology and biostatistics, engineering, and outreach and advocacy. Aimed at undergraduates and graduate students, trainees who participate in CIRP’s programs attend project and mentorship meetings, screen and enroll research project participants, submit protocols, and manage data.

CIRP also has several programs specifically for undergraduates studying behavioral science, education, engineering, injury prevention, or related fields. Supported by the National Science Foundation, the Research Experiences for Undergraduates (REU) program offers student-scholars the chance to collaborate with CIRP mentors over the course of an intensive 10-week summer schedule. Living on the University of Pennsylvania campus, REU trainees work with their mentors while attending workshops, seminars, and field trips, while receiving training in research ethics and conducting studies.

“As fully integrated research team members, student trainees work alongside CIRP scientists helping to advance the science toward creating positive impact on the lives of children, adolescents, and young adults,” said CIRP training manager Carol Murray, MSS, MLSP. During fiscal 2013, 47 trainees took part in CIRP’s programs, including 40 undergraduates, Murray said.

Speaking at the Research Institute’s annual Scientific Symposium, CHOP Research Chief Scientific Officer and Executive Vice President Philip R. Johnson, MD, noted how CHOP Research's educational programs positions the institution to meet the training challenges posed by decreased federal funding for research.

Another CHOP Research program, the CHOP Research Institute Summer Scholars Program, which has a special emphasis on advancing translational pediatric research, “brings undergraduates into the Research Institute and shows them how great science is,” Dr. Johnson said.

“These programs are the way we will build the future generation of scientists,” Dr. Johnson said.