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Hematology and Oncology

Pediatric and Adult Physicians Collaborating to Improve Cancer Survival Among Adolescents and Young Adults

Dr. Julie Wolfson is the founder of the Adolescent and Young Adult Oncology and Oncofertility Program at Children’s of Alabama.

It might surprise many people to learn that cancer survival rates have been showing continual improvement in children under 14 and mature adults, but not among the 15-to-39-year-old age group. The Adolescent and Young Adult (AYA) Oncology and Oncofertility Program at Children’s of Alabama is aiming to change that.

When Julie Wolfson, M.D., MSHS, pediatric oncologist at Children’s of Alabama and founder of the AYA Program, was learning about healthcare delivery a decade ago, she noticed the survival disparities for adolescents and young adults and began to investigate how it could be addressed. She researched registry data and found that across a host of different diagnoses, survival rates were better when patients treated at a National Cancer Institute-designated Comprehensive Cancer Center.

She began to focus her research on understanding why. And she became determined to ensure the highest level of care for adolescents and young adults at Children’s of Alabama. In 2018, using seed money from the Hyundai Hope on Wheels Foundation, Wolfson launched the AYA program, which provides clinical treatment support and an array of psychosocial support services vital for patients in the adolescent to young adult stage of life.

“These patients are in a really vulnerable time in their social, emotional and physical development,” Wolfson says. “While their friends are at college, they have to come home. They were independent, and suddenly, they’re back under their parents’ roof, or they’re working and they don’t have help. When their peers keep growing and doing normal young adult things, they’re stalled, and they don’t feel well.”

To address these issues, the AYA Program offers wraparound, multidisciplinary services. “An AYA social worker meets with every patient to figure out what they can help with that is AYA-specific. They also connect with their assigned hematology-oncology social worker and the Hope and Cope Program for any psychosocial support needs or provides resources outside the institution,” Wolfson explains.

Preserving Fertility for Young Adults with Cancer

Unfortunately, getting treatment for cancer can put patients at risk for not being able to have their own children later on. One of the things that Wolfson is trying to do through her partnership with the director of fertility preservation is increase the number of patients who undergo fertility preservation. “The director and I are very much partners in this, and she bends over backwards to get our kids in,” Wolfson said. The oncofertility program allows young patients to bank sperm or extract and preserve eggs. Soon, they will also be able to take advantage of a relatively new process that allows for cryopreservation of ovarian tissue that can be re-implanted later when they are ready to have children.

Wolfson also reports that survival improvement in the AYA group is correlated to clinical trial participation, so enrolling AYA patients into as many clinical trials as possible is a key focus area for the program. “Our treatment and our care of these patients only has a chance to get better if they’re treated in a research study,” Wolfson said. “When you look at pediatric oncology, well over 70% to 75% of the patients are enrolled in a clinical trial, but it’s very different the older patients get.” As the patients age, the proportion of those who are enrolled in clinical trials drops. For this reason, Wolfson tries to ensure the AYA group has access to appropriate trials.

Ultimately, everyone’s mission is to ensure that each patient gets the best treatment possible. “This age group can walk through either door—pediatric oncology or adult oncology,” Wolfson said. As a result, the pediatric oncology team works hand-in-hand with their counterparts on the adult oncology staff to make sure all patient care options are examined. This interdisciplinary approach is carried out at monthly tumor board meetings and with paired disease specialists—one from the pediatric side, one from the adult side—who bring a deeper understanding to leukemia, lymphoma, sarcoma, neuro-oncology, genitourinary and gynecological oncology and more. Radiologists, pathologists and other specialists also bring their expertise to bear.

Since AYA’s launch, Wolfson has received investments from the O’Neal Comprehensive Cancer Center and the Vestavia Hills High School service-learning project, RISE.

“It’s outstanding to have the support of the leadership from Children’s of Alabama, as well as University of Alabama at Birmingham and the O’Neal Comprehensive Cancer Center,” Wolfson said. “It’s pretty unique.”

January 16, 2023 by childrensal

Hematology and Oncology

Improving End-of-Life Care for Pediatric Cancer Patients

Dr. Emily Johnston is a pediatric oncologist at Children’s of Alabama.

Almost 3,000 children die from cancer each year in the United States. But in pediatrics, unlike adult care, there are no quality measures for end-of-life care. That’s changing, however, thanks to the pioneering work of Children’s of Alabama pediatric oncologist Emily Johnston, M.D., M.S.

“My goal is to establish quality measures for end-of-life care for children with cancer and then leverage those quality measures to reduce disparities in care,” Johnston said.

The mission comes from her time as a fellow, when she saw many deaths that did not go the way she believes patient families would have wanted. Systemic issues, like the inability to get a child into hospice given the lack of pediatric hospices, presented significant barriers.

In researching pediatric end-of-life issues, she found significant variation in care for underrepresented minorities. For instance, Hispanic children with cancer are more likely than non-Hispanic white children to die in the hospital and have medically intense end-of-life care. “When I would say this to people, they would tell me, ‘It’s okay, it’s what they want,’” Johnston said. But through dozens of interviews with bereaved parents, she found that was not the case.

During one series of interviews with 28 parents of 24 children who died of cancer, most parents said they preferred a home death and did not want their child dying in the restrictive environment of the intensive care unit (ICU). While they wanted their children to die peacefully, parents didn’t want to stop cancer treatment. They also told interviewers that they needed more education around end-of-life issues and more support around non-medical issues, such as financial challenges, so they could focus on their child. Parents also talked about a sense of abandonment after their child died.

Johnston and her colleagues then brought together a panel of nine experts in pediatric oncology, including representatives from nursing, social work and palliative care, to develop quality measures for end-of-life care for children with cancer, much like those available for adults. The 16 measures fit into four categories:

Avoiding medically intense end-of-life care
The location of death
Hospital policies/programs
Supportive care

For instance, one indicator measures the proportion of children who were intubated during the last 14 days of life, given that intubation usually increases suffering. Another measures the proportion of children who received palliative care or hospice support in the last month of life since both offer an additional layer of support for families, help alleviate suffering and facilitate the identification of the goals of the family and child.

Hospital policies designed to improve the patient end-of-life experience included having pediatric palliative care services and a bereavement program available and eliminating visiting-hour restrictions, including age and number of visitors. Johnston and her colleagues are now working on validating and implementing the quality measures.

But, she said, “that research is a very big-picture; it’s not going to affect care tomorrow.” So, she partnered with University of Alabama at Birmingham palliative care physician Susan Buckingham, M.D., to improve access to palliative care for patients with high-risk cancers such as some brain and solid tumors.

Today, instead of starting palliative care near the end of a child’s life (and then only if the parent or physician requests it), families meet with Buckingham at diagnosis and have access to palliative care services throughout their child’s illness. Meanwhile, Buckingham attends oncology staff meetings and is now part of the multidisciplinary team treating those patients. She can spot unmet needs early in the process and work collaboratively with the nurses, social workers and other clinicians caring for the child and family. “We’ve done interviews with 12 families who had early palliative care about their experiences, and the feedback has been really positive,” Johnston said. As one family told her, “I didn’t really understand what palliative care did until we needed it, and I was so glad I already knew them by then.”

January 16, 2023 by childrensal

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.

September 5, 2022 by childrensal

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, MD; Emily 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.

September 5, 2022 by childrensal

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.

September 2, 2022 by childrensal

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.

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.

February 15, 2022 by childrensal

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.

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.

February 15, 2022 by childrensal

Hematology and Oncology, Inside Pediatrics

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

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.”

February 15, 2022 by childrensal

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.

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 Oncology. They 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.”

February 15, 2022 by childrensal

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’s is 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/.

August 27, 2021 by childrensal

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