Browsing Category

Hematology and Oncology

Hematology and Oncology, Inside Pediatrics

New BMT Program Director Focused on Expanding Immunotherapy

Joseph Chewning, MD, is the clinical director of the Pediatric Blood and Marrow Transplantation program at Children’s of Alabama.

As Joseph Chewning, MD, takes over as the clinical director of the Pediatric Blood and Marrow Transplantation (BMT) Program at Children’s of Alabama, he has an eye toward the program’s future, especially when it comes to immunotherapy.

It’s a field that Chewning says is growing very quickly. CAR-T cell therapy, in particular, is changing the paradigm for blood cancer treatment. With CAR-T, the child’s own immune cells are programmed to recognize and destroy a patient’s cancerous cells. Children’s became certified in 2018 to provide the therapy to children and young adults with recurrent acute lymphoblastic leukemia (ALL). As the new clinical director of the pediatric BMT program, Chewning wants to make sure Children’s can use CAR-T and other immunotherapies to help as many patients as possible.

“That’s really the goal for the program going forward—to continue to expand the novel treatments that we can provide for the children of Alabama, including cellular therapies,” he said.

One of the major advantages of immunotherapies is that, while they do have side effects, they’re typically less toxic than bone marrow transplant. For that reason, Chewning believes they’ll continue to become more common.

“At some point I think these cellular therapies will eclipse bone marrow transplant in usefulness,” he said. 

Chewning’s focus on immunotherapies is one part of his overall goal of providing the best quality care for patients in the safest way possible. 

“It’s really important to me that we fulfill the responsibility we have to the children of our state,” he said. Chewning wants to bring cutting-edge therapies to Children’s so families in Alabama won’t have to travel to get them.

“I’ve got four kids of my own,” he said. “I can’t imagine having a sick child who needs life-saving therapies and then having to separate from the rest of my family and go four or five states away.” 

In addition to serving as director of the BMT program, Chewning is the medical director for patient safety.

Hematology and Oncology, Inside Pediatrics

Solid Tumor Program Features Many Experts With One Goal

Elizabeth Alva, MD, directs the solid tumor program at Children’s of Alabama and the University of Alabama at Birmingham.

The pediatric solid tumor program at Children’s of Alabama and the University of Alabama at Birmingham (UAB) is made up of experts from several specialties who work together to achieve one goal: provide the best care possible for patients with solid tumors.

“There are so many advances happening today in pediatric oncology,” Elizabeth Alva, MD, director of the program, said. “It’s helpful to create a niche in which you have a team that’s knowledgeable with good expertise in that area.” 

The program is part of the Children’s hematology/oncology department. Alva is joined by fellow oncologists Jamie Aye, MDEmily Johnston, MD; and Kimberly Whelan, MD. The team also includes advanced practice nurse practitioners and specialists from surgical oncology, orthopedic oncology, radiation oncology, palliative care and developmental therapeutics, as well as emotional support and psychosocial services.

One of the team’s objectives is to standardize care while still individualizing it. A key component of that is identifying the best clinical trials for their patients, something they do during their monthly “protocol” meetings. They also treat children with high-risk disease, such as neuroblastoma, with a comprehensive search of the literature to ensure everyone is up to date on the latest therapies and scientific findings, and then develop practice standards. “We’re making sure that we’re all focused on getting those patients the best care they can have,” Alva said.

The team also aims to increase participation in national consortiums of pediatric cancer centers to bring additional state-of-the-art care and innovative research to patients at Children’s. “Children’s and the University of Alabama at Birmingham are well recognized as a good center, but we want to continue to improve our national presence and our recognition as a top-notch program,” Alva said.

One area where that’s already happening is with the tumor xenograft project directed by Aye and pediatric surgeon Elizabeth A. Beierle, MD, in conjunction with others at UAB. Since the project’s inception in 2013, 175 patients have agreed to let the researchers implant their tumors into an animal model—a much more accurate way of studying these diseases. The goal is to better understand how the tumors behave and identify treatments that not only halt the cancer growth but have fewer side effects than current therapies.

Hematology and Oncology, Inside Pediatrics

Hope and Cope Program Helps Families Navigate Medical Journeys

With the diagnosis and treatment of childhood cancer or serious blood disorders like sickle cell disease comes an emotional rollercoaster for the child and the family. From practical issues including getting to appointments, caring for siblings, and managing the costs of care to psychosocial issues such as anxiety, fear, grief, and even anger, there are needs beyond the medical support physicians and nurses can provide. That’s where Children’s of Alabama’s Hope and Cope Psychosocial and Education Program comes in. The program provides emotional support and services using a family-centered approach in which the family and healthcare providers work together to best meet the needs of the entire family. 

“It is becoming more and more important to provide these services to families dealing with cancer and serious blood disorders,” program director Avi Madan-Swain, PhD, said. “Even if we cure the disease medically, for some the cost of cure is high and results in neurocognitive difficulties as well as psychological difficulties, such as post-traumatic stress disorder.” 

To reduce stress during hospitalizations or clinic visits, the Hope and Cope Psychosocial and Education Program offers inpatient schooling (either group or bedside); art, music, and animal-assisted therapy; parental consult service; a weekly inpatient caregiver dinner support group; and expressive activities such as drumming, drama, and journaling. 

The program’s education/school liaisons help patients transition back to school, maintaining communication between the medical team, the child’s school, and the family and providing education to schools and families about special services the child may need. This includes classroom presentations to help classmates understand the child’s diagnosis and treatment. 

Once a child is diagnosed with cancer or a serious blood disorder, families complete a screening questionnaire to help the team identify immediate needs. The team shares the results with the family and initiates evidence-based interventions to address identified needs. The overall goal is to prevent crises by intervening early rather than being reactive. The team then meets weekly to discuss the psychosocial needs of newly diagnosed patients and those who have relapsed and need close monitoring. They also talk about any difficulties the patient/family may be experiencing in the inpatient unit or outpatient clinic.

“We’re building wellness and resiliency,” Madan-Swain said. “We’re not just looking at family risk factors, but also their strengths, and developing plans to support young people and their families to manage the challenges of their medical journey, make the most of their strengths, and ultimately celebrate life.”

A new initiative is strengthening psychosocial service delivery for parents of children undergoing bone marrow transplant, Madan-Swain said. “I’ve been working to systematically standardize parent assessment and education and providing psychosocial resources because of the intensity of the process. It’s like being in a pressure cooker.”      

One thing that sets Hope and Cope apart from similar initiatives at other children’s hospitals, according to Madan-Swain, is its bereavement component. Services begin when the disease is no longer treatable and continue for two years after a child’s death. All family members work with art and music therapists to create a “legacy piece,” such as a painting, sculpture, or music. For instance, the music therapist may record the child’s heartbeat and place it in a bear for the family. “We found that families who work on meaning-making activities cope much better after the loss of the child,“ Madan-Swain said. “This has really pushed us in the direction of making sure that we’re not waiting until the very end to create a legacy piece.”

Despite the success of the program, Madan-Swain is not resting. “I always want to move on to developing psychosocial care pathways based on family risk level and providing evidence-based interventions and expressive activities to improve adjustment and quality of life for both our oncology and hematology patients and their families,” she said. 

Hematology and Oncology, Inside Pediatrics

Hematology/Oncology Fellowship Programs on a Growth Spurt  

Left to right, Katie Metrock, M.D., Hilary Haines, M.D., and Kimberly Whelan, M.D. All are pediatric oncologists at Children’s of Alabama and faculty members in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

Left to right, Katie Metrock, M.D., Hilary Haines, M.D., and Kimberly Whelan, M.D. All are pediatric oncologists at Children’s of Alabama and faculty members in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

Every year, two pediatric residents are accepted to Children’s of Alabama’s three-year, ACGME-accredited program. Their first year is a whirlwind of rotations through the inpatient, stem cell transplant, and outpatient clinics, said Kimberly F. Whelan, M.D., who completed the fellowship herself and now directs the program. “I think of it as being a very rewarding but steep learning curve year,” she said. In the second and third years, the fellows develop an area of research or scholarly focus that serves as the foundation for their first faculty position.  

“We send our fellows out to institutions all across the country,” Dr. Whelan said. “And as that number has grown, it’s been wonderful to see the opportunities for networking and collaboration and the impact our fellows are having on the field — not only here in Birmingham, but across the country.” 

The program typically gets about 40 applicants a year and interviews between 20 and 25. With COVID, of course, interviews have gone virtual, which has pros and cons, Dr. Whelan said. “The upside is it’s more convenient for the applicants since they don’t have to take as much time off to travel. And in the virtual interview you’re able to talk with them and get a good sense of what their interest is, where their passion lies, what they’re looking for in the program.” 

The downside, however, “is that we don’t get to show off Birmingham and the beautiful Children’s of Alabama, which is such a wonderful institution.” 

Recently, the Hematology/Oncology Program added two additional fellowships for hematology/oncology fellowship graduates who want additional training: one in bone marrow transplantation and one in neuro-oncology.  

Bone Marrow Transplant Fellowship 

While hematology/oncology fellows receive training in bone marrow transplant, the field has become very subspecialized, requiring specialized education, said Hilary Haines, M.D., who directs the bone marrow transplant fellowship. “The field as a whole is moving away from general hematology/oncology [and] into subspecialities, so the need to have dedicated training in these fields is definitely evolving,” she said. 

That’s why the division created the one-year fellowship program focused entirely on bone marrow transplantation. It’s one that interests many hematology/oncology fellows, said Dr. Haines, given the complexity of the field. “You get to care for a variety of patients and be involved with cutting-edge technology and new therapies.”  

Indeed, bone marrow transplants are not just for blood cancers. Today they are an option — even a cure — for other blood disorders like sickle cell anemia and severe combined immunodeficiency, bone marrow failure, and some neurological diseases. “We’ve identified more diseases that are curable via bone marrow transplant, and our outcomes have improved for the procedure, so we’re more willing to pursue transplant for diseases that we may not have in the past,” Dr. Haines said. 

Several large children’s hospitals already offer bone marrow transplant fellowships, she said, so having the option at Children’s of Alabama serves as a good recruitment tool for hematology/oncology fellows who may eventually want to focus on bone marrow transplantation.  

The first participant, who completed her hematology/oncology fellowship at Children’s, should finish her training in May. 

Neuro-oncology Fellowship 

Like Dr. Haines, Children’s neuro-oncologist Katie Metrock, M.D., points to the continued subspecialization in hematology/oncology as the reason for the new, one-year neuro-oncology fellowship she just launched. “The year is meant to submerge you into the field of neuro-oncology,” she said, which is vastly different from hematology/oncology overall. “Fellows get significant exposure to leukemia and lymphoma and other solid tumors during the general hematology/oncology fellowship, but not as much in-depth experience with neuro-oncology because the program operates slightly differently,” she said.  

Since patients often require comprehensive care from multiple medical specialties, the extra year is designed to enhance a fellow’s knowledge of pediatric brain tumors, including diagnosis, biology, clinical course, treatment options, outcomes, and areas of research. 

“In addition,” Dr. Metrock said, “the field is rapidly evolving as we learn more and more information about these tumors. This gives the fellow extra time to learn the details of the complex care required to help these children succeed.” 

Brain tumors are the most common pediatric tumors and the one with the highest mortality rate. In brain tumors, the neuro-oncologist coordinates the team of specialists required to care for these children, including neurosurgeons, neuropathologists, radiation-oncologists, neurologists, ophthalmologists, and others. The fellow will start by watching the neurosurgeon operate, then follow the tissue sample in the pathology lab, learn to discuss a neuro-ophthalmology exam with the ophthalmologist, understand the dosage and design behind radiation-oncology plans, and meet with palliative care, among other rotations — a deep dive they don’t get during their hematology/oncology fellowship.  

That experience is different from just meeting the patient and family after the surgery and diagnosis. “We feel we can better understand what’s going on with them — to the extent that’s possible — by following them from the beginning,” Dr. Metrock said. 

“My favorite year in all my training was my neuro-oncology fellowship,” she said. “It was a year when I was able to do what I loved most and ask every question I wanted to ask. I’m excited to offer that to other people.” 

The first neuro-oncology fellow starts in July 2022. 

Hematology and Oncology, Inside Pediatrics

Children’s of Alabama Welcomes Pediatric Neuropsychologist Specializing in Neuro-Oncology 

Emily A. H. Warren, Ph.D., is a pediatric neuropsychologist at Children’s of Alabama and an assistant professor in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

Emily A. H. Warren, Ph.D., is a pediatric neuropsychologist at Children’s of Alabama and an assistant professor in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

With or without cancer, childhood is a very important time for brain development. Yet the experience of cancer itself, as well as the cognitive effects of many cancer treatments, can derail that development, leaving kids at risk for long-lasting social, psychological, and cognitive challenges.  

“The great thing is that with the wonderful advancements in medical treatments and the comprehensive care these children receive, most will survive,” said Emily A.H. Warren, Ph.D., who came to Children’s of Alabama in the fall of 2021 as its first neuropsychologist dedicated specifically to caring for pediatric brain tumor patients. “Now there can be much more attention focused on quality of life, neurocognitive development, and long-term outcomes like educational attainment.” 

Children’s diagnoses and treats more than 60 new central nervous system tumors a year. Dr. Warren uses her expertise in brain development and neuroanatomy to evaluate cognitive development in children with brain tumors. “My main goal is to provide families with a high-quality neuropsychological evaluation, so I can help them understand the potential impact of their child’s brain tumor diagnosis and treatments on cognitive and psychosocial outcomes and support their child in pursuing their goals,” she said. 

Her work begins with a comprehensive neuropsychological assessment covering everything from intellectual functioning to learning, memory, attention, executive functioning, processing speed, visual motor skills, and psychosocial adjustment. 

“With that data, I can help families understand how a diagnosis like a brain tumor and treatments like surgical resection, radiation, and chemotherapy can affect brain development and cognitive abilities,” she said. The goal of the assessment is to carefully evaluate a child’s cognitive strengths and weaknesses to promote the development of age-appropriate skills. Once she knows each child’s unique cognitive profile, Dr. Warren helps families identify ways to support their child. Supports could include developing an individualized education program (IEP) and other school-based or community interventions such as physical therapy, social skills training, or psychological therapies. 

“These children are going through so many complex challenges,” she said. “There are the social and emotional aspects of the diagnosis and treatment, which can be very hard on families. We also need to support their school reintegration because some of these children have been out of school for a while.” Additionally, children may have new functional deficits. They might be in a wheelchair, have visual or hearing impairment, “or just feel that their thinking is slower than it used to be, or they are having trouble getting their words out,” Dr. Warren added. 

“I like to spend a lot of time helping families understand the relationship between their child’s cognitive abilities and their academic achievements and social interactions. It is also important to help families understand the social and emotional impact of being a cancer survivor.”  

Dr. Warren’s research focuses on cognitive and social outcomes following radiation therapies for brain tumor survivors. “With advances in radiation technology, such as proton radiation, children tend to have better neurocognitive and developmental outcomes than we saw in the past,” she said.  “Even so, we still routinely see challenges with skills such as attention, executive functions, and processing speed. Children who receive more intensive therapies might be at greater risk for cognitive challenges. This is why it’s important to individually tailor each neuropsychological evaluation to meet the needs of each child.” 

Dr. Warren hopes to collaborate with her colleagues in pediatric oncology and radiation oncology to continue this research and is currently a co-investigator for a clinical trial exploring whether memantine, a drug used in Alzheimer’s disease, is neuroprotective in children receiving brain radiation.  

Hematology and Oncology, Inside Pediatrics

Bench-to-Bedside: Translational Focus Moves Sickle Cell Research into Clinic Faster 

Lebensburger_WEBSITE

Jeffrey Lebensburger, D.O., is a pediatric hematologist at Children’s of Alabama and an associate professor in the Division of Hematology/Oncology in the Department of Pediatrics at the University of Alabama at Birmingham.

Basic research is conducted in labs and on animal models, and clinical research is conducted in humans. Traditionally, the two don’t mix, with the basic happening before the clinical. Translational research, a mix of the two, is designed to get new discoveries and treatments to patients faster. “Translational research is a vital component to making breakthroughs in clinical care,” said Jeffrey D. Lebensburger, D.O., who directs the pediatric hematology section of Children’s of Alabama’s Department of Hematology and Oncology. 

Dr. Lebensburger and his research partner, University of Alabama at Birmingham assistant professor Malgorzata Kasztan, Ph.D., are using this approach to find better ways to prevent early kidney disease in children with sickle cell disease. Between 20 percent and 30 percent of children with the disease already demonstrate kidney injury before they hit their teens, and up to 70 percent will develop chronic kidney disease by the time they’re middle-aged. Many will require dialysis or transplantation, often beginning in their 20s. However, the most commonly used test for kidney problems rarely identifies early signs. 

“While we may think that the kidneys are doing okay in childhood based on the tests, there may be severe damage that leads to this early dialysis, which is why we greatly need this bench-to-bedside approach to prevent progression early in adulthood,” Dr. Lebensburger said.  

“We are particularly interested in looking at which patients are at risk for kidney disease and if there is a way to identify those patients early in the process, so they can get better care,” said Dr. Kasztan. 

Tracking the progression from childhood through adulthood, however, would take too long and cost too much. Yet mice genetically engineered to have sickle cell disease fully mature in just a few months, making them a perfect model for exploring kidney disease progression. 

Using these mice, coupled with a biobank of patient blood and urine samples and a sophisticated assay for kidney damage available only in the research setting, Drs. Lebensburger and Kasztan identified high levels of the protein endothelin-1 (ET), which binds to two receptors, ETA and ETB, as a key contributor to early kidney damage. Blocking the ETA receptors with an already-FDA-approved drug, however, protected the mouse kidneys. 

“That allows us to bring back to the patient what we’re seeing in the mouse model and understand if it will continue into adulthood,” Dr. Kasztan said. “Then we could potentially intervene earlier.” 

At the same time, biomarkers of early damage they find in the human blood and urine samples can be “mirrored” in the mouse model to confirm the results, she said. Then interventions that work in the animal model can be tested in patients.  

This type of bidirectional work provides the foundation for clinical trials in humans, said Dr. Lebensburger. “That’s an example of this bench-to-bedside approach: It works in the mouse model of sickle cell, so we can lobby the FDA to start a clinical trial in humans.” 

Hematology and Oncology, Inside Pediatrics

Children’s Pediatric Oncologists Spearhead Registry of Children with Cancer, COVID 

Left, Julie Wolfson, M.D., and right, Emily Johnston, M.D., are pediatric oncologists at Children’s of Alabama and assistant professors in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics. Left, Julie Wolfson, M.D., and right, Emily Johnston, M.D., are pediatric oncologists at Children’s of Alabama and assistant professors in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

Left, Julie Wolfson, M.D., and right, Emily Johnston, M.D., are pediatric oncologists at Children’s of Alabama and assistant professors in the Division of Pediatric Hematology/Oncology in the University of Alabama at Birmingham Department of Pediatrics.

What started as a conversation among a Facebook group of pediatric oncologists at the pandemic’s start has now grown into the largest registry of children with cancer and COVID-19 in the country, providing invaluable information for healthcare providers grappling with the effects of the virus on their patients. 

“People started posting in the Facebook group about caring for children with cancer and COVID-19, asking what they should do,” said Children’s of Alabama pediatric oncologist Emily Johnston, M.D., who, with her colleagues Julie Wolfson, M.D., and Jenn Levine, M.D., of Cornell Medical Center in New York, helped found the Pediatric COVID-19 Cancer Case (POCC) Report. “There were no data, no guidelines, nothing,” Dr. Johnston said. The registry, which is now housed at the University of Alabama at Birmingham, is led by Drs. Johnston and Wolfson.  

The growth has been “miraculous,” Dr. Johnston said. “We started these conversations in March 2020 and had our first patients entered by the end of April, representing an incredible pace.” Today, the registry has data on more than 1,400 children from more than 100 sites. “The other hospitals are participating in the registry because it’s the right thing to do for our community and our patients,” she said. “The national collaboration has been really impressive.” 

One goal of the registry is to provide real-time information to pediatric oncologists. The team sends regular data briefs to every pediatric cancer site in the country with updated summaries. 

In December 2021, the group published its findings on 917 children from 94 U.S. hospitals in the prestigious Journal of Clinical OncologyThey found these children had a high risk of severe infection, with one-third admitted to the hospital and 9 percent to the ICU. They also found nearly half (45 percent) had their cancer therapy changed because of the infection. Fourteen (1.5 percent) died from COVID-19.  

The children most likely to develop severe disease with COVID-19 infections were age 11 or older; those with health conditions in addition to their cancer; and those with neutropenia (low white blood cell count) or hematologic cancers. Hispanic children were most likely to be infected and to have their cancer therapy modified, even though they didn’t have more severe illness. This, Dr. Johnston said, mirrors the racial and ethnic disparities seen in the wider population with COVID-19.  

She and her colleagues are working on understanding why Hispanic children were more likely to have their treatment changed. “This may reflect a combination of systemic issues, biological issues, and even our innate biases. It’s probably a combination of all these, and definitely something we need to tease apart to figure out why this is happening.” 

Dr. Johnston and her team are now collecting data on the vaccination status of all patients, including those in the registry, and the impact of vaccination on infection. They also have a small grant to delve deeper into the data, including to assess how COVID-19 in children with cancer has changed over the course of the pandemic and determine the impact of the virus on long-term health. 

An important area they hope to research focuses on the impact of treatment changes. “We’ve had such incredible improvements in survival in the last several decades in part because we’ve gotten more treatments and escalated treatment, including giving more intense, frequent chemotherapy,” Dr. Johnston said. “That’s led to improved survival. We get very nervous when we have to hold or modify chemotherapy.” 

The two Drs. Johnston and Wolfson said they feel a calling for the work. “We felt it was our duty to use our research infrastructure for this public health purpose,” said Dr. Wolfson. “Hopefully, we’ll be able to help patients and clinicians as much as possible.” 

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

BrandiPernell-Asthma-SickleCell_Research-Resized

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

DrFriedman-Lab-Microscope-Resized

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.