Hematology and Oncology

There’s the pediatric cancer population, those younger than 15. And the adult cancer population, those 40 and older. And then there’s the “in-between” patients, those ages 15 to 39, defined as adolescents and young adults (AYA), who sometimes seem as if they’ve left behind when it comes to the dramatic improvement in cancer outcomes.

“Even though they may have the same diagnosis as the 14-and-under group and the 40-and-older group, we haven’t seen the same improvement in survival as the other groups,” said Julie Wolfson, M.D., assistant professor of pediatrics in the University of Alabama at Birmingham (UAB) School of Medicine Institute for Cancer Outcomes and Survivorship.

In talking to adolescents and young adults with cancer, she said, “you learn that they’re not getting things that are important to them.” This includes financial and psychosocial support, as well as information on fertility preservation. They’re also not enrolling in clinical trials, “and we know that outcomes correlate with clinical trial enrollment.”

To address the problem, the hematology/oncology teams at UAB and Children’s of Alabama developed the Adolescent and Young Adult Oncology program for these “in-between” patients.

The team received seed funding in 2018 from Hyundai Hope on Wheels to develop the program’s infrastructure. The Vestavia Hills High School Rebels Impact through Service and Engagement (RISE) program, through the O’Neal Comprehensive Cancer Center, helped raise money for the program, enabling its expansion.

Nearly 200 AYAs have participated so far. Patients are matched with potential clinical trials and receive fertility preservation counseling and a psychosocial screen from the program’s adolescent and young adult social worker. An online support group for those 25 and younger is available.

A group of specialists from each cancer type meet in a monthly (now virtual) tumor board. “Patients really benefit from us all sharing our knowledge,” Wolfson said. Indeed, research shows improved outcomes with greater collaboration between adult and pediatric health care providers.

The feedback from the health care teams and the patients and families has been very positive, she said. “Patients express relief that someone ‘gets it,’” Wolfson said. “That they’re not a 5-year-old who wants to look at the goldfish and they’re not a 65-year-old with grandkids. There’s a lot of emotion involved and to process all that with someone at their developmental level is really important for them.”

None of this would have been possible without the leadership from the pediatric and adult hematology/oncology programs, she said. “Every AYA program looks different but ours is one of the more comprehensive I’ve seen across the country because we have amazing, collaborative clinicians. If people weren’t willing to play together in the ‘sandbox’ the way they are it wouldn’t be as successful.”

Although the story of pediatric cancer over the past 20 years is one of success, there are still areas where the news remains grim, particularly for pediatric solid tumors. In addition, the therapies used to treat pediatric cancers can have long-lasting consequences and even increase the risk of other cancers.

Which makes identifying novel agents with better outcomes and fewer side effects so critical. Enter the xenograft approach, in which cancer tissue taken from the child is implanted into an animal model, allowing for more precise targeting of potential therapies.

“There are xenograft models in the adult population to find novel agents, but the pediatric model is very rare,” said Elizabeth A. Beierle, M.D., a pediatric surgeon at Children’s of Alabama who focuses on pediatric surgical oncology. She, along with pediatric hematologist-oncologist Jamie M. Aye, M.D., run one of the few pediatric xenograft programs in the country out of Children’s.

“These patient-derived xenografts more closely mimic what’s going on in the human,” said Beierle. Otherwise, researchers have to use cells from tumors gathered more than 50 years ago and cultured under artificial conditions. “A lot of those tumors lost the genetic and phenotypic characteristics from the original tumor,” she said. “So when we try to investigate new drugs, we often see that what happens in the tissue culture is not what’s happening in humans.”

Plus, testing compounds in a petri dish misses the reality of a cancer in a living model, including the cells that surround the tumor and the blood vessels.

The xenograft process takes time: six months to a year before the tumors grow and experiments can begin. But seven years after the Children’s initiative began, several therapies are showing promise, with some ready to move into Phase 1 clinical trials.

One is a viral therapy for pediatric solid tumors that infects tumor cells and releases an inflammatory cytokine that attracts other inflammatory cells to attack the tumor cells. Another inhibits a protein found in pediatric liver tumors.

The barrier to clinical trials, said Beierle, is funding. While the program has received strong support from community organizations, more is needed.

One thing that isn’t a problem is obtaining the biopsy tissue for the xenograft bank. “We’ve never had a family say no,” said Aye. “They understand that the research may not affect their child, but they hope it will help other children.”

Up to 70 percent of adults with sickle cell anemia will develop chronic kidney disease, many of whom will require dialysis or transplantation. But since the damage often begins in childhood, identifying the early signs of kidney disease could shift that trajectory.

That’s the goal of Jeffery Lebensburger, D.O.’s research at Children’s of Alabama, for which he was recently awarded a prestigious National Institutes of Health R01 grant. Julie Kanter, M.D., who co-directs the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham (UAB), is also involved.

“This project will develop a novel approach to monitoring changes in kidney function over time that is specific for patients with sickle cell anemia,” said Lebensburger, who directs UAB’s hematology section in the Division of Pediatric Hematology. “This will improve our clinical capacity to identify sickle cell anemia patients who are at risk for chronic kidney disease and who may benefit from additional prospective therapies.”

The early signs of kidney disease are usually silent. By the time obvious markers like protein in the urine develop, the loss of kidney function is often too advanced to reverse. “We need to control it in childhood,” Lebensburger said. Particularly since people with sickle cell anemia who go on dialysis are eight times more likely to die from kidney-related complications within seven years than those without the disease.

“Given the high mortality early in life from kidney disease, it is vital that we monitor kidney disease progression in children and adults,” he said. But the standard glomerular filtration rate (GFR) blood test provides, at best, a “guess” of kidney function. The tests also weren’t developed for sickle cell patients, he said. The gold standard, a measured test of how well the kidney eliminates a contrast agent, takes four to six hours and is very expensive.

“For us to appropriately track kidney function in this population and prevent the devastating complications of renal disease in our patients, we need a GFR equation that is validated for those with sickle cell, not for other populations,” Lebensburger said. Which is what his research is designed to do.

“We’re starting from scratch to develop this,” he said, performing normal blood work in 200 children and 200 adults and then developing a new calculation of kidney function that is valid for our sickle cell patients. “Then we’ll know what’s happening and can better track patients’ kidney function and prevent the devastating effects of kidney disease.”