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Hematology and Oncology

Hematology and Oncology, Inside Pediatrics

Bringing Groundbreaking Cancer Trials to Alabama Children

Left, Elizabeth Alva, M.D., and right, Katie Metrock, M.D.

Although there have been great strides in treating pediatric cancer, it remains the leading cause of death by disease among children. In addition, more than 95 percent of childhood cancer survivors have significant health-related issues because of the toxicity of current treatment options. Yet just 4 percent of government spending on cancer goes to pediatric cancer.1 

That’s why the Sunshine Project is so important. The project, part of the National Pediatric Cancer Foundation, brings together more than 20 children’s hospitals, including Children’s of Alabama, with the goal of streamlining the process required to bring new, less toxic, more effective pediatric oncology drugs to clinical practice. 

Children’s joined the consortium in 2020 and is already participating in several novel studies for some of the worst pediatric cancers. The ultimate goal is to “provide hope to families,” said Children’s oncologist Elizabeth Alva, M.D. 

One such trial is for patients newly diagnosed with metastatic fusion-positive rhabdomyosarcoma, which has a three-year, event-free survival rate of just 6 percent. “Traditionally, we inundate these patients with very intensive therapy,” said pediatric oncologist Katie Metrock, M.D., but outcomes are still dismal. Research has traditionally focused on intensifying that therapy, but sometimes that just leads to greater toxicity without improving outcomes, said Dr. Alva.  

This uniquely designed study, called the EVOLUTION trial, is based on evolutionary theories around adaptation and resistance. Patients will be enrolled into one of four arms based on shared decision-making between the family and clinicians—not randomization. The first arm is standard of care. The second arm is “first strike therapy,” which Dr. Alva compares to a “meteor hitting the Earth and killing all the dinosaurs.” This approach addresses the hypothesis that children relapse because once the chemo-sensitive cells are gone, a more resistant population emerges. “So the first-strike theory is to get rid of everything,” she said.  

A third arm focuses on maintenance, or a “second strike”: providing the standard of care until the patient is in remission and then switching to a less-intense maintenance therapy to keep those resistant cells at bay while restoring quality of life. 

The fourth arm provides adaptive therapy. This means starting with standard chemotherapy that starts and stops based on response and adaptive timing of therapy, with a goal of increased time to progression rather than complete remission.  

Children’sis also participating in a phase 2 study evaluating the use of digoxin, a decades-old drug typically used in patients with heart failure, for patients with recurrent/refractory medulloblastoma. The drug was identified as potentially beneficial in laboratory and animal studies. 

“It is exciting to think that there are well-known drugs that can be repurposed to help treat various cancers,” said Dr. Metrock. “Our hope is that the tumors will show response to digoxin, and it could potentially be added to other up-front regimens in the future.” While the drug is well tolerated in children,” she said, “we haven’t used it in this heavily pretreated population, so we need to see how our patients do with it.” 

Two other trials are exploring immunotherapy. One is testing the immunotherapy nivolumab in combination with azacitidine for children with recurrent, refractory osteosarcoma. The other is exploring a vaccine made from the patient’s own cancer cells designed to trigger the immune system to target the cancer for destruction in children with high-grade gliomas. Trials such as these are coordinated by the Clinical Trials Office at Children’s of Alabama, which was established in 2019 to increase access to new therapies for Alabama children, thanks to a lead gift from the Hugh Kaul Foundation.

Projects like the Sunshine Project are desperately needed, said Dr. Alva. “Unfortunately, pediatric cancer doesn’t get the same degree of funding as adult cancer. It’s rare, but when it strikes in a pediatric population, so many more years of life are lost.” 


1 National Pediatric Cancer Foundation. Facts about Childhood Cancer. Available at: https://nationalpcf.org/facts-about-childhood-cancer/

Hematology and Oncology, Inside Pediatrics

Asthma, Sickle Cell Disease and Trauma – Connecting the Dots

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Brandi M. Pernell, DNP, assistant professor of Pediatric Hematology and Oncology

Take a child with sickle cell disease who is already at a significantly higher risk for asthma, pain and acute chest syndrome—the leading cause of death in these children—and mix in adverse childhood experiences (ACEs) such as violence, racism, abuse, parental death or divorce. The result: sicker children who, due to toxic stress exposures, are more likely to experience poorer health outcomes. 

That’s what Brandi M. Pernell, DNP, an assistant professor of pediatric hematology and oncology who works at the Children’s of Alabama dedicated pediatric sickle cell clinic, found in her research. 

“The literature shows that those who experience ACEs early in life have a higher risk of chronic conditions like asthma, cardiovascular disease, and obesity”—even cancer, Dr. Pernell said. But until her work, there was limited documentation in the sickle cell literature about ACEs. What is known is that acute stress is a common trigger for pain episodes in children with sickle cell disease. Pernell is now connecting the dots to show that ACEs increase asthma risk in these children which, in turn, leads to an increased risk for pain and acute chest syndrome.  

Her findings highlight the need to screen children with sickle cell disease, particularly adolescents, for ACEs and, if found, implement protective factors and buffering mechanisms to address the physiologic sequelae from these toxic exposures. 

She’s already begun that process, teaming with the local chapter of the Sickle Cell Foundation to promote social and emotional competence and resilience among affected adolescents. That community-based approach is important, she said. “I believe we need to meet families and patients where they are,” she said. And the Foundation has a different relationship with patients and families than the clinic staff. “We address the medical side, but ACEs are things happening in the home and neighborhood,” said Dr. Pernell. 

For Dr. Pernell, the work is more than a scientific endeavor; it’s personal. She felt called to this research, she said, both as a Black woman (sickle cell primarily affects Black people) and as a healthcare provider, particularly given the events of 2020. “In the wake of COVID and the social and racial uprising prior to and throughout 2020, it just spoke to me,” she said. So when she joined the University of Alabama at Birmingham faculty in 2016, this is where she focused her research. “I can relate to my patients in a way that some others can’t,” she said. “I’ve experienced some of the same things they have.”  

“If not me, then who?” she asked, quoting the late congressman and civil rights leader John Lewis. “If not now, then when?”  

Hematology and Oncology, Inside Pediatrics

Oncolytic Herpes Virus Immunotherapy Shows Early Promise in Pediatric Patients with High-Grade Glioma

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Gregory Friedman, M.D., professor of pediatrics at the University of Alabama at Birmingham (UAB), director of developmental therapeutics for the Alabama Center for Childhood Cancer and Blood Disorders at UAB and Children’s of Alabama

It’s a pretty big deal when your research is published in the New England Journal of Medicine. But it’s just as rewarding when your research holds promise for treating one of the most deadly cancers seen in children: high-grade gliomas.  

“Unfortunately, outcomes are very poor for children with progressive gliomas, and we have not seen a significant improvement in outcomes for this dreadful disease in the last 30 years,” said Gregory Friedman, M.D., professor of pediatrics at the University of Alabama at Birmingham (UAB), director of developmental therapeutics for the Alabama Center for Childhood Cancer and Blood Disorders at UAB and Children’s of Alabama and lead author of the paper, “Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas.” Dr. Friedman also presented the findings from the phase 1 trial during the virtual American Association for Cancer Research Annual Meeting in April 2021. 

“The toxicities associated with the current standard therapies are unacceptably high,” Dr. Friedman said. “There is, therefore, a great need for effective and less toxic targeted therapies for these children.” 

Dr. Friedman’s team used a genetically engineered cold-sore virus, a herpes simplex virus type-1 (HSV-1), which naturally infects cells of the peripheral and central nervous system. While the modified virus, called “G207,” can’t infect and harm normal cells, it can target tumor cells by directly killing the cells and stimulating the child’s own immune system to attack the tumor.  

Twelve patients between 7 and 18 years old with high-grade gliomas that had progressed on prior treatments received an infusion of G207 through intratumor catheters. Within 24 hours, some also received a single, small radiation dose directed to their tumors, which was designed to enhance virus replication and spread throughout the tumor.  

Treatment response was assessed by imaging, tumor pathology and the patient’s performance status. Eleven of the 12 patients demonstrated a response, with a median overall survival of 12.2 months; a 120 percent increase over the typical overall survival of 5.6 months in this population. To date, 36 percent of patients have survived longer than 18 months, surpassing the median overall survival for newly diagnosed pediatric high-grade glioma.  

To date, immunotherapies have failed to improve outcomes in pediatric brain tumors because the tumors are “cold,” with very few immune cells needed to attack the tumor, Dr. Friedman said. “Importantly, when examining matched pre- and post-treatment tissue from patients, we showed something that has not been seen before with any other therapy: that G207 dramatically increased immune cell trafficking to the tumors and turned the ‘cold’ tumors to ‘hot’ ones. This is a critical step in the development of an effective immunotherapy for children with brain tumors,” he said.   

G207 alone or in combination with radiation therapy was well tolerated, with no dose-limiting toxicities, grade 3/4 treatment-related adverse events, or evidence of virus shedding into the bloodstream, saliva, or conjunctiva.  

“While further investigation in a phase 2 clinical trial is needed, our findings suggest that oncolytic immunovirotherapy using a modified cold-sore virus is a safe and potentially efficacious approach to target pediatric high-grade glioma,” Dr. Friedman said. 

Hematology and Oncology, Inside Pediatrics

ICOS Research Advances to Benefit Survivors, Improve Outcomes

By numbers alone, the Institute for Cancer Outcomes and Survivorship at the University of Alabama School of Medicine has posted an impressive list of accomplishments: Just six years after its founding, ICOS has received funding or commitments for $40 million, up $30 million since 2019. Additionally, faculty members have published approximately 500 journal papers, 167 of those in just the last year.

But the mission of ICOS far transcends those numbers. In their quest to study cancer outcomes long-term and identify issues survivors face, institute members – who include epidemiologists, physician-scientists, behavioral scientists, molecular biologists and nurse-scientists – have aggressively pursued research questions aiming to help survivors prevent and manage long-term complications from cancer and its treatment.

“Institute members are asking some terrific, clinically pertinent questions and going after them like a dog after a bone,” said ICOS Director Smita Bhatia, M.D., M.P.H., who’s also the Gay and Bew White Endowed Chair in Pediatric Oncology at the University of Alabama at Birmingham (UAB). “Really changing practice to improve clinical outcomes – that’s our goal.”

Over the past two years, notable ICOS studies have produced clinically useful results as well as spawned new and related research. Bhatia offered updates on several key efforts:

  • Examining the molecular basis of long-term complications in pediatric cancer survivors: Boosted by a sizable 7-year grant from the National Institutes of Health, ICOS researchers have “unearthed some very interesting genes associated with chemotherapy that cause heart failure,” Bhatia reported. “They’ve also developed a risk prediction model that allows us to say, ‘If you have this genetic makeup, we can predict whether you’ll develop heart failure or not.’”
  • Testing strategies to improve adherence to oral chemotherapy among adolescents with acute lymphoblastic leukemia (ALL): Physicians texted patients each night to remind them to take their chemotherapy, with a duplicate text sent to parents. Parents were instructed to watch their children take the medication. Families also watched educational videos on the topic. “Among adolescents at baseline who were non-adherers, they benefited most with this intervention,” Bhatia said. “Those findings were published and we’re now taking this to the next level in a 2,000-patient trial.”
  • Understanding how to treat older cancer patients without undue toxicity: Geriatric assessment surveys were given to older adults with colorectal cancer, multiple myeloma and other malignancies that are pinpointing how a patient’s total fat and muscle tissue may be linked to treatment toxicity levels. “This is like a gold mine in terms of giving us so many good findings we can apply in clinic,” Bhatia said.
Hematology and Oncology, Inside Pediatrics

Robust LLH Program Continues Expanding, Raising Profile

With an overarching goal of improving cure rates while decreasing treatment toxicity and side effects, the Leukemia, Lymphoma and Histiocytosis (LLH) program at Children’s of Alabama has nearly doubled in size over the past decade as faculty members continue raising its national and international profile and spearheading innovative clinical trials and research.

            The LLH program includes five physicians and four nurse practitioners within the Division of Pediatric Hematology and Oncology, which includes more than 25 faculty. LLH clinicians consult on about half of the new cancer diagnoses seen each year at Children’s, said Director Matthew Kutny, M.D., also an associate professor of pediatric hematology and oncology at the University of Alabama at Birmingham (UAB).

            LLH faculty members published 34 research articles in peer-reviewed journals over the last two years and presented more than 30 times at national oncology meetings. Additionally, several members sit on national steering committees or review boards that develop pediatric cancer treatment guidelines, Kutny said. The LLH program also participates in several key clinical trial consortiums, such as the National Cancer Institute’s Children’s Oncology Group, including selected membership in a network studying the newest oncology treatments in children.

            “Our faculty has expanded, but we’ve also gained greatly in our expertise,” Kutny explained. “When children come here with a particular diagnosis, they’re not just treated by a general hematologist or oncologist, but rather, through our disease-specific teams.”

            “We have providers who really understand that disease and are involved at a national level in developing the best treatments for that disease,” he added.

            Kutny’s own research efforts include leading several national trials in myeloid leukemias as well as focusing on central nervous system disease in acute myeloid leukemia. Other notable faculty research efforts include:

  • Aman Wadhwa, M.D., M.S.P.H.: Working with Smita Bhatia, M.D., M.P.H., Wadhwa is examining how body composition affects childhood cancer outcomes in lymphomas, with an eye toward predicting and modifying toxicities.
  • Wayne Liang, M.D., M.S.: With a dual appointment in bioinformatics, Liang is harnessing the power of big data via electronic health records to better match patients to appropriate clinical trials, among other efforts.
  • Julie Wolfson, M.D., M.S.H.S.: Involved in many local and national projects, Wolfson is concentrating on outcomes disparities in adolescents and young adults with cancer, an at-risk group not often incorporated into clinical trials.
  • Ana Xavier, M.D.: Leading several national trials in difficult-to-treat lymphomas, Xavier is also focusing on reducing the burden of chemotherapy and radiation exposure in lymphoma patients.
Hematology and Oncology, Inside Pediatrics

Membership in Elite Consortium Offers Many Benefits to Researchers, Patients

MEMBERSHIP IN ELITE CONSORTIUM OFFERS MANY BENEFITS TO RESEARCHERS, PATIENTS

            Children’s of Alabama has become the only institution in the state – and among an elite group nationally and internationally – to be accepted into a unique clinical trials consortium focusing on personalized therapy approaches for children with malignant brain tumors.

            Accepted into the Pacific Pediatric Neuro-Oncology Consortium (PNOC) in December 2020, Children’s membership in this distinguished group offers many advantages to researchers, clinicians, and ultimately to young patients, said Girish Dhall, M.D., director of the Division of Pediatric Hematology, Oncology, and Blood & Marrow Transplantation.

            The consortium is comprised of about two dozen sites across the United States, Canada, Europe and Australia. Unlike other consortia, PNOC’s clinical trial portfolio includes neurosurgery trials with techniques such as convection-enhanced delivery, fluorescent agents and advanced imaging compounds.

            “The only way to get access to certain cutting-edge or state-of-the-art clinical trials is to be invited by a drug company working on a multi-institution trial or in trials run by these consortia,” Dhall explained. “This means we have access to a multitude of open trials and our patients don’t have to go out of state to be enrolled in trials testing promising experimental drugs that are not yet FDA-approved.”

            In addition to prestigious trial access, PNOC enables basic and translational scientists at Children’s and University of Alabama at Birmingham (UAB) to propose new trials of candidate drugs or therapies and fosters collaboration among them and researchers at other institutions, said Dhall, who was a founding member of PNOC about eight years ago when based in Los Angeles.

            PNOC is unusual because of its focus on personalized therapies for children with brain tumors that aims to improve survival while reducing toxic, treatment-related side effects, he noted.

            “Traditionally we use chemotherapy or radiation therapy for these cancers, but both just kill rapidly dividing cells and don’t discriminate between cells inside the cancer and cells that might normally be rapidly dividing inside the body,” he said. “The focus has shifted to understanding specifically what makes these cancer cells grow and divide by studying the DNA, RNA and protein inside the cancer cells to develop therapies that improve the efficacy but reduce toxicity to normal cells at the same time.”

            Of PNOC’s current open clinical trials, Children’s will launch its participation in two: One in children with a uniformly fatal tumor called diffuse intrinsic pontine glioma, or DIPG; and another that combines two drugs for children with refractory or recurrent low-grade gliomas, “a population in which this is like a chronic disease and they progress from one therapy to another, so it’s important for them to have multiple options,” Dhall said.

Hematology and Oncology, Inside Pediatrics, Neurology & Neurosurgery

Children’s of Alabama Launches Second Groundbreaking Trial of Viral Treatment for Brain Tumors

Children’s of Alabama and the University of Alabama at Birmingham are leading studies using a genetically re-engineered herpes virus to treat pediatric high-grade gliomas.

“A uniformly dismal prognosis.” That’s how Children’s of Alabama neurosurgeon James M. Johnston, Jr., M.D., describes what children with recurrent malignant brain tumors face, with an average lifespan of six months given a lack of effective treatments.

Now Johnston, in collaboration with Greg Friedman, M.D., associate professor of pediatric oncology and director of Developmental Therapeutics at Children’s, is leading groundbreaking studies designed to shift that trajectory. The team recently completed a Phase 1 immunotherapy clinical trial of genetically re-engineered herpes virus G207 to treat pediatric high-grade gliomas. Their work builds on adult research on the viral treatment pioneered by James Markert, M.D., MPH, who chairs the Department of Neurosurgery at the University of Alabama at Birmingham (UAB), as well as Friedman’s laboratory work, which showed the virus was more effective against pediatric brain tumors than adult tumors.

In the past three years, 11 patients with high-grade gliomas have traveled to Children’s from throughout the country, Mexico and Canada to participate in the study. They receive special screening to pinpoint the tumor location, which is then biopsied. Johnston then places three to four catheters in the tumor. The next day, Friedman and his team infuse the genetically-modified virus into the brain through the catheters.

“We think the virus works by directly killing the tumor cells,” Johnston said, as well as activating the immune system to destroy any remaining cells. “Brain tumors have a way to hide from the immune system by making themselves immunologically ‘cold,’” he explained. The herpes virus turns a “cold” tumor into a “hot” tumor and generates the immune response. Indeed, months after the surgery tests show that immune cells have infiltrated the tumor and continue killing tumor cells.

The initial phase 1 trial in patients with high-grade gliomas was designed to demonstrate safety and wasn’t powered to show efficacy. Nonetheless, Johnston said, “our median survival was significantly longer than the historical six months,” with several children now long-term responders.

In late December 2019, the team received a three-year, $750,000 R01 grant from the U.S. Food and Drug Administration for a Phase 1 trial in malignant cerebellar brain tumors, which may be even more sensitive to the virotherapy than the gliomas. At the same time, they are submitting grants for a Phase 2 multicenter trial of the virus therapy for recurrent malignant supratentorial tumors.

Johnston stresses that the research is a team effort, involving basic scientists, oncologists, surgeons, nurses and intensivists. “It’s an ‘all-hands-on-deck’ kind of thing,” he said.

Hematology and Oncology, Inside Pediatrics

Charting New Ground in Treating Blood Clots in Infants

UAB assistant professor of pediatrics and Children’s of Alabama hematologist-oncologist Hope Wilson, M.D., is researching long-term anticoagulation for high-risk children thanks in part to a American Society of Hematology fellowship.

Venous thromboembolism (VTE) is an increasing problem in pediatrics and can be associated with significant morbidity. Although most children are at low risk for recurrence, some have ongoing risk factors, which increases their risk for having further thrombosis. Yet there is no specific guidance on the optimal duration of treatment for such patients.

Well, not yet, anyway. But if research from Children’s of Alabama hematologist-oncologist Hope Wilson, M.D., is successful, that question will have an answer.

This year, Wilson was named one of 23 American Society of Hematology (ASH) Clinical Research Training Institute (CRTI) participants, a prestigious award that will help fast track her research on long-term anticoagulation for high-risk children. The fellowship is a unique, year-long education and mentoring program for hematology fellows and junior faculty at academic medical centers with the opportunity to interact “with the finest in the field,” Wilson said.

Throughout the year, Wilson will receive intense review and critical feedback on her project. The goal is to have a polished proposal to submit for external funding at the end of the program. But the proposal is just the beginning of what the grant means for her career. “There is a lot of greatness that can happen as a result of the exposure,” she said, including lasting mentorship relationships and critical networking opportunities for potential future collaborations.

The CRTI program kicked off virtually in August, focusing on the foundation, methodologies, and application of patient-oriented clinical research. Participants will meet regularly throughout the year concluding in May 2021 at ASH headquarters in Washington, D.C.

Wilson’s interest in this topic came, in part, from the patients she sees in Children’s new pediatric thrombosis clinic, which she helped develop. The overall goal of the thrombosis program is to improve care for children affected by VTE. To this end, the team has worked to develop protocols and algorithms to standardize treatment for these children, who come from throughout Alabama as well as neighboring states. In just the past year, more than 100 patients have passed through the clinic, many with recurrent clots. 

That’s the population she’s focused on in her research. “Findings from this research will help fill this knowledge gap and provide critical data to inform clinical decision making, changing the way that we manage children who require long-term anticoagulation,” she said.

Hematology and Oncology, Inside Pediatrics

Addressing the Unmet Needs of Adolescent and Young Adult Patients With Cancer

Julie Wolfson, M.D., assistant professor of pediatrics at UAB and Children’s of Alabama, helped develop the Adolescent and Young Adult (AYA) Oncology Program.

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.”

Hematology and Oncology, Inside Pediatrics

Xenograft Program Discovering New Therapies For Pediatric Cancer

Elizabeth Beierle, M.D., center, and Jamie Aye, M.D., right, run one of the few pediatric xenograft programs in the U.S. out of Children’s of Alabama.

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.”