A mere 10 to 15 percent of older adolescents (ages 15 to 19) with cancer are enrolled in clinical trials—a far lower proportion than younger pediatric cancer patients. Some of the more common cancers seen in adolescents are similar to adult cancers, but most adult oncology clinical trials exclude patients younger than 18. The Federal Drug Administration, however, is now recommending that adolescents ages 12 to 17 be eligible for adult oncology trials when the investigational or approved drug being tested is appropriate for their cancer.
Ami Desai, MD, MSCE, is making sure this happens. Desai sees young adult patients with sarcomas or other advanced solid tumors in the Medical Oncology Phase 1 Clinic, where they are evaluated for early phase clinical trials and are followed medically once they are enrolled in a trial. As the liaison between the pediatric and adult oncology programs, Desai keeps Comer Children’s pediatric oncologists informed of open adult oncology trials at the University of Chicago that may be a good fit for their young adult patients. “I can inform and enroll adolescents and young adult (AYA) patients on these clinical trials that may not be open or available on the pediatric side,” says Desai.
There is a strong history of collaboration between the pediatric and adult oncology teams at the University, which ensures that the AYA population is treated with the most effective therapies. Pioneering studies conducted by Wendy Stock, MD, the late James Nachman, MD, Tara Henderson, MD, MPH, and Jennifer McNeer, MD, MS, have demonstrated that for some types of cancer, such as leukemia and Hodgkin’s lymphoma, AYA patients have better outcomes when treated with regimens from pediatric clinical trials rather than adult regimens.
I can inform and enroll adolescents and young adult (AYA) patients on these clinical trials that may not be open or available on the pediatric side.
~ Ami Desai, MD, MSCE
Desai also uses her knowledge of upcoming investigator-initiated studies in medical oncology to advocate for patients younger than 18 to be included as participants when the treatment is relevant to their cancer type or to molecular alterations found in their tumors. In addition, she is developing new pediatric oncology trials based on data and experience from adult oncology trials, with a focus on investigating immunotherapies.
“One of the strengths of our pediatric oncology research program is the strong connection we have with the adult oncology research team,” says Desai. “We share the same institutional review board and electronic medical record system, which helps foster the necessary collaboration to drop the age limit for some cancer studies and enable access to treatment for our adolescent and young adult patients with relapsed or refractory cancers.”
A hematopoietic stem cell transplant can transform the life of a child with severe sickle cell disease (SCD), potentially curing the devastating condition that carries a high risk of stroke, acute chest syndrome, excruciating crises that require prolonged hospitalizations and mortality. But less than 5 percent of children with SCD have a human leukocyte antigen (HLA)-identical sibling who can donate blood and bone marrow stem cells that mitigate the risk of transplant complications such as graft versus host disease (GVHD).
“We’ve been searching for approaches to increase the donor pool so that more children might benefit from stem cell transplants without suffering from severe complications,” says John M. Cunningham, MD, director of Hematopoietic Stem Cell Transplantation and chair of the Department of Pediatrics. Cunningham was one of the first transplant physicians in the country to perform hematopoietic stem cell transplants with matched sibling donors for children with SCD in the 1990s. The University of Chicago Medicine has successfully transplanted children with matched unrelated donors, but the chance that an African American child with SCD will find a suitable donor from the National Marrow Donor Program is less than 30 percent, says Cunningham.
The pediatric stem cell transplant team has also explored haploidentical transplants from partially matched family members—usually parents, but sometimes siblings—using a procedure called CD34+ cell selection, which employs a commercially available antibody to remove T cells from the stem cell transplant to decrease the risk of GVHD. “We’ve done haploidentical transplants on a compassionate basis for children with severe SCD, but we haven’t been able to eliminate complications of the transplant,” says Cunningham.
As we continue to improve outcomes for transplants, we want to identify all the children who will benefit from them.
~ John M. Cunningham, MD
A novel allogenic stem cell transplant currently being used in Europe, however, has shown considerable promise in reducing the risk of GVHD. “This new strategy involves further engineering the graft to minimize GVHS, which will allow us to offer a much safer and more effective treatment for SCD using haploidentical parent donors,” says Cunningham, who anticipates that a study examining the new approach will open at UChicago Medicine in spring 2018. Although initial candidates for the treatment will be children with severe forms of SCD, the therapy, if successful, may be applicable to a broader group of SCD patients, as well as to children with malignant diseases such as leukemia and with non-malignant diseases such as thalassemia, aplastic anemia and immune deficiencies.
Transplant physicians at UChicago Medicine are also refining transplant eligibility criteria for children with less severe SCD. “As we continue to improve outcomes for transplants, we want to identify all the children who will benefit from them,” says Cunningham. Adolescents and young adults with SCD at UChicago Medicine, for example, are participating in the multicenter STRIDE2 trial, which compares stem cell transplant outcomes using HLA-identical siblings or matched unrelated donors with patients receiving standard of care.
Although cancer remains the leading cause of death among children past infancy, childhood cancers account for less than 1 percent of all cancers diagnosed each year. The small number of pediatric cancer cases means fewer technological advancements in treatment driven by synthesizing “big data.” And the pediatric data that do exist are often hard for scientists to access and analyze.
“We’ve always had the problem in pediatric cancer that there are just not enough data to study,” says Samuel Volchenboum, MD, PhD, MS, director of the University of Chicago Center for Research Informatics (CRI). But Volchenboum and other University of Chicago researchers are hoping to solve that problem by creating a comprehensive pediatric cancer data commons (PCDC) that centralizes data and makes them easily accessible to the entire cancer research community.
In 2004, the International Neuroblastoma Risk Group (INRG) Task Force, co-chaired by Susan Cohn, MD, chief of the Section of Pediatric Hematology/Oncology, began the task of standardizing and centralizing data from 8,800 patients with neuroblastoma. But the data were in a large spreadsheet that required a lengthy approval process to access. The clinical data were also not linked to patient genomic data, and researchers could not easily determine the availability of patient biospecimens housed at the Children’s Oncology Group biorepository in Columbus, Ohio.
We realized the power that comes from putting all the data in one place.
~ Samuel Volchenboum, MD, PhD, MS
In 2012, Volchenboum and Cohn set out to overcome these limitations by using philanthropic funding to turn the INRG neuroblastoma data into a “living” database housed on a searchable website. “We realized the power that comes from putting all the data in one place,” says Volchenboum, who hopes the PCDC will do the same for other types of pediatric cancer.
In 2015, the CRI established a partnership with the University’s Center for Data Intensive Science, directed by Robert Grossman, PhD, the Frederick H. Rawson Professor of Medicine and Computer Science. Through this partnership, they integrated the INRG Data Commons with the National Cancer Institute’s Genomic Data Commons—housed at UChicago and led by Grossman—and the National Center for Biotechnology Information’s Gene Expression Omnibus. This linked available genomic data with the INRG database’s de-identified clinical patient information, such as basic demographics, tumor profile and treatment regimen. The searchable database now houses data from more than 19,000 neuroblastoma patients from around the world.
With the appropriate funding, Volchenboum believes the team can get the PCDC running in two or three years. He hopes it will encourage more data sharing among researchers and help inform the design of future clinical trials. “The PCDC has the promise of leveraging the success of the INRG to other pediatric cancers, accelerating research and hopefully improving survival,” adds Cohn.
The University of Chicago Medicine is one of the first institutions in the Midwest certified to offer chimeric antigen receptor T-cell, or CAR T-cell, therapy for pediatric acute lymphoblastic leukemia (ALL). The rapidly progressing leukemia primarily affects children and young adults, from age three to 25. This cancer relapses or is refractory when treated with chemotherapy in 20 percent of cases.
CAR T-cell therapy involves genetically re-engineering a patient’s T cells, then letting these cells multiply in the laboratory. While awaiting their T cells, patients receive chemotherapy designed to clear the way for the newly armed T cells. Once the modified T cells are infused into the patient, they search for leukemia cells and destroy them. More than 80 percent of pediatric patients with B-cell ALL treated in CAR T-cell clinical trials throughout the country went into remission.
“CAR T-cell therapy has revolutionized the treatment of acute lymphoblastic leukemia,” according to Michele Nassin, MD, assistant professor of pediatrics. “We need focused treatments like this that can eradicate particular types of cancer.”
CAR T-cell therapy presents a risk of serious, potentially life-threatening side complications, including high fever and neurological side effects. The Federal Drug Administration requires special certification for every site offering the treatment to confirm that the institution is well-suited to handle these potential adverse reactions.
This type of immunotherapy has been investigated in clinical trials at UChicago Medicine to treat B-cell lymphoma and acute lymphoblastic leukemia in adults. Nationwide, patients treated with CAR T-cell therapy doubled their long-term survival rate, and 40 to 50 percent appear to have lasting complete remissions. Pediatric oncologists at UChicago Medicine are now working with their colleagues who treat adults to provide the therapy to adolescents and young adults in addition to pediatric patients.
CANCERS WE TREAT
BLOOD DISEASES WE TREAT
Riyue Bao, PhD
Viviana Berthoud-Barrandeguy, PhD
Alexandre Chlenski, PhD
Rena M. Conti, PhD
Joanna Gemel, PhD
Kyle M. Hernandez, PhD
Anoop Mayampurath, PhD
Jorge Andrade Ortiz, PhD