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hematology and oncology

Hematology and Oncology, Inside Pediatrics, Pulmonology

Solving the Mystery of Lung Disease in Children with Sickle Cell Disease

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Children’s of Alabama pulmonologist Ammar Alishlash, M.D.

If lung disease is the leading cause of death in children with sickle cell disease, then why aren’t pulmonologists more involved in their care earlier? That’s a question Children’s of Alabama pulmonologist Ammar Alishlash, M.D., wanted to answer. “I felt for us to take care of those patients, especially those with underlying lung disease, would serve them better clinically,” Dr. Alishlash said. 

In the past, the leading cause of death in those with sickle cell disease was infections. But the use of prophylactic antibiotics changed that. Today, it’s acute chest syndrome (ACS), marked by shortness of breath, low oxygen levels and fever. Many patients progress to respiratory failure, and some die. Yet lung specialists are not usually involved in their care while in the hospital or after discharge. Instead, in most children’s hospitals they are managed solely by hematologists. 

“The problem is, we don’t have any specific treatment targeted for acute chest syndrome,” said Dr. Alishlash. Instead, patients are managed with supportive therapy, including oxygen, fluids, antibiotics and sometimes invasive or non-invasive ventilation. 

Now Dr. Alishlash is on a mission to change that dynamic. He’s launched a three-pronged research initiative: identifying risk factors for ACS to proactively recognize children with a higher risk, developing clinical pathways to prevent progression and mortality and researching novel therapies to treat the condition. 

“I became interested in this condition because I feel that, as pulmonologists, we have experience with other lung diseases,” he said. “We can apply our knowledge from other lung diseases to the sickle cell population, which could open a lot of doors for diagnosis and new treatments.” 

So far, Dr. Alishlash has instituted a clinical pathway to standardize the care children with ACS receive after admission. The pathway has been in place for about 18 months, and the results are encouraging, with a nearly 50 percent reduction in length of stay. In addition, all patients have survived. Previously, one out of every 100 children would die. “That’s pretty significant, especially when you’re talking about children, who are typically between 2 and 4 years of age when they are most likely to develop ACS,” he said. 

Dr. Alishlash has also made progress in identifying risk factors for ACS in children with sickle cell disease. One is nocturnal hypoxemia, when oxygen levels drop at night. This seems to induce the sickling and is associated with increased risk of ACS.1 He also found a correlation between the neighborhood where patients live and ACS, due to, he thinks, air quality, socioeconomic factors and greater stress.2 

On the laboratory side, Dr. Alishlash and his team are using a sickle cell mouse model to test potential treatments as well as identify triggers. One interesting finding is that chlorine can cause sickling, leading to the release of heme from red blood cells, which is toxic to the lung endothelium and subsequent development of ACS. A medication called hemopexin, however, scavenges the free heme. When given to mice exposed to chlorine who developed ACS, hemopexin reduced the death rate from 80 percent to 20 percent.3 

At the same time, Dr. Alishlash has started a twice-monthly clinic for sickle cell patients with underlying lung disease. The clinic is very busy, he said. “And patients’ outcomes are improving, which is very encouraging.” 


1 Nourani AR, Rahman AKMF, Pernell B, et al. Nocturnal hypoxemia measured by polysomnogram is associated with acute chest syndrome in pediatric sickle cell disease. J Clin Sleep Med. 2021;17(2):219–226.

2 Alishlash, AS, Rutland, SB, Friedman, AJ, et al. Acute chest syndrome in pediatric sickle cell disease: Associations with racial composition and neighborhood deprivation. Pediatr Blood Cancer. 2021; 68:e28877

3 Alishlash AS, Sapkota M, Ahmad I, et al. Chlorine inhalation induces acute chest syndrome in humanized sickle cell mouse model and ameliorated by postexposure hemopexin. Redox Biol. 2021;44:102009. doi:10.1016/j.redox.2021.102009

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. 

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

Children’s of Alabama Ramps Up Pediatric Oncology Research Program

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The faculty of the Pediatric Hematology, Oncology, and Blood and Marrow Transplantation program at Children’s of Alabama and the University of Alabama at Birmingham (UAB). The program is currently working to offer more potentially life-saving clinical trials to patients.

It’s only been a year since Girish Dhall, M.D., moved from Los Angeles, where he was an associate professor of pediatrics and director of the Neuro-Oncology Program at Children’s Hospital Los Angeles, to Birmingham to become division director for the Pediatric Hematology, Oncology, and Blood and Marrow Transplantation program at Children’s of Alabama and the University of Alabama at Birmingham (UAB). Yet he’s already made significant progress on one of his key goals: offering more potentially life-saving clinical trials to patients.

“We’re trying to increase our research portfolio through multiple mechanisms,” he said. Children’s already belongs to the largest pediatric cancer research organization in the world, the Children’s Oncology Group (COG), an international consortium of more than 200 children’s hospitals, universities, and cancer centers. Children’s of Alabama and UAB participate in the COG Phase I Consortium, the Neurofibromatosis Consortium and the Next Consortium, all of which conduct cutting-edge clinical trials for pediatric patients with nervous system tumors.

While COG is a major force in pediatric oncology, the number of trials it offers is limited. With about 150 new cancer patients a year seen at Children’s of Alabama, Dhall said, more opportunities are needed. “Even though we’ve come from a survival rate of zero 50 or 60 years ago to nearly 70 percent, 30 percent of patients still relapse,” he said.

Thus, Children’s of Alabama and UAB joined the Sunshine Project, which is a part of the National Pediatric Cancer Foundation. It emphasizes basic and translational research in the areas of bone and soft tissue sarcoma and brain tumor immunology, Dhall said. In addition, Children’s of Alabama and UAB are joining the ReMission Alliance Against Brain Tumors (RAABT), a University of Florida-led network of neuro-oncology, tumor immunology and genetics experts from top peer institutions as well as a community of vested collaborators and influencers affected by brain cancer.

To manage the expected growth in clinical trials, Dhall is also reorganizing the department’s clinical trial infrastructure to improve efficiency and recruiting additional staff to prepare for the anticipated increase. He also wants to add other scientists who can build on the department’s portfolio not just in brain tumors, but also in sickle cell disease and leukemia. “That’s my hope for the next year,” he said.

He predicts that the number of clinical trials, today at about 10, will double within the next two years.

“Patients who relapse after front-line therapy have a very poor prognosis with poor survival,” Dhall said. “So, for us to be able to offer treatment options here means they don’t have to travel to other sites like Atlanta or Memphis, which is a huge disruption for patients at the end of life.”

“As a physician,” he said, “this gives me hope and it keeps me going.”

 

Hematology and Oncology

Cancer Predisposition Clinic Aims to Change the Trajectory of Genetically Based Cancer

Li-Fraumeni syndrome. Von Hippel-Lindau. Rhabdoid tumor predisposition syndrome. Beckwith-Wiedemann syndrome. Retinoblastoma.

These are just a few of more than a dozen rare genetic conditions that predispose a child to cancer. Overall, at least 10% of children with cancer harbor a disease-associated pathogenic variant in a known cancer predisposition gene. While few can be prevented, regular surveillance can, at the very least, find malignancies early when treatment is most effective.

That’s the idea behind Children’s of Alabama’s Cancer Predisposition Clinic, now in its third year.

“We  provide comprehensive care and screening for these patients with the goal of detecting cancers at an early stage in order to provide the best care and outcomes for the patients,” said Elizabeth Alva, M.D., assistant professor in the University of Alabama at Birmingham (UAB) Division of Pediatric Hematology and Oncology. “It used to be there was nothing we could do about this terrible diagnosis,” she said. “Now we know there are definitely ways to look for cancers early and help patients.”

In addition, the clinic provides psychological support for families and determines if the genetic condition affects other family members, she said.

Typically, primary care physicians follow children with cancer predispositions. But those doctors may not be aware of or able to provide the level of evidence-based surveillance that Alva offers.

That’s why these clinics are a growing area in the pediatric hematology/oncology world, particularly at the larger children’s hospitals. “We felt that we definitely needed to provide that same level of care here in Alabama,” Alva said.

Alva and neuropsychologist Avi Madan-Swain, Ph.D., are currently following about 25 patients. Patients come to them through the pediatric cancer genetics clinic, where families are tested and counseled. Alva provides the screening, which ranges from regular ultrasounds to CT scans and MRI, while Madan-Swain addresses the family’s psychological needs.

One benefit to the clinic is that if there is a cancer diagnosis, the child and family are already comfortable with the hospital and the clinical team.

Alva is building a database of patients to gain a better understanding of disease development and progression, while Madan-Swain plans research around the psychological impact on families that have a child with a predisposition syndrome.

Understanding Genes
Learn more about the UAB Department of Genetics.

Hematology and Oncology

Pain Clinic Provides Safe Space for Sickle Cell Patients to Receive Treatment

Raven Myrick, CRNP, right, places a virtual reality headset on patient Olivia Parker in Children’s of Alabama’s Sickle Cell Pain Clinic.

Throbbing. Sharp. Pounding. Dull. Stabbing. Cutting. Gnawing.” That’s how patients describe the pain of sickle cell disease.[1]

While current guidelines call for patients to receive pain medications within an hour of arriving at a treatment center or emergency room (ER), that’s difficult to achieve in a busy emergency department (ED), said Jeffrey Lebensburger, D.O., MSPH, who directs the Cancer and Blood Disorders’ hematology section at Children’s of Alabama. This delay in pain relief allows the pain intensity to increase and may lead to a child requiring hospitalization. In addition, in this era of an opioid epidemic, more families report discrimination when they ask for opioids for pain and are accused of drug-seeking behavior.

That’s why Children’s started its own sickle cell pain clinic, Lebensburger said. It’s not just for patients in crisis. “About half our patients also experience daily, chronic pain,” he said.

Targeting Pain

The clinic has four main goals:

  • Provide care in a familiar setting
  • Reduce the number of hospitalizations
  • Get the patient’s pain under control more quickly
  • Provide non-medicine treatment strategies for pain

The clinic is run out of the regular pediatric hematology clinic with a dedicated nurse practitioner, Raven Myrick, CRNP. Patients can call a hotline or email the hematology team any time and get a same-day or next-day appointment. Eventually, the team would like to offer night hours.

“Our families appreciate being able to go to the clinic versus the ER,” Myrick said. “It’s a familiar, nonjudgmental atmosphere. It’s not our job to say if they are having pain or not. Our job is to make them feel comfortable and to show that we care.”

“It’s not a cure for their disease,” she said, “but the pain clinic gives them hope that someone is working to make them feel better.”

Virtual Reality as Treatment

The clinic uses Starlight Virtual Reality (VR) headsets, donated to Children’s of Alabama by the Starlight Children’s Foundation, to teach kids how to relax and breathe through the pain. Studies have found that VR can reduce pain sensation. When patients come to the clinic, they first spend at least 10 minutes with a VR deep breathing/visualization program. Then they can continue to use other programs as a distraction technique or even just watch movies. “Being able to watch Netflix in the virtual reality environment without cues from other people provides superior distraction to non-virtual reality distraction,” Lebensburger said. Then they go home with a list of relaxation apps to download on their phones.

Patients also receive pain kits to help with distraction, including items like squeezable balls and Silly Putty, as well as their own “tools,” such as action figures and trading cards that they can only play with during a pain crisis.

The clinic has seen more than 30 patients since it opened in Marchand had just three hospitalizations, which is “an amazing outcome for our patients,” Myrick said.

“We know our patients and are familiar with what works for them with use of our Individualized Pain Plans,” Myrick said.

Cancer Fighters

Get more information about the Cancer and Blood Disorders Program at Children’s of Alabama.


[1] Ballas SK, Gupta K, Adams-Graves P. Sickle cell pain: a critical reappraisal. Blood. 2012;120:3647-3656;

Hematology and Oncology

The Institute for Cancer Outcomes and Survivorship Focuses on Key Quality-of-Life Issues

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As more patients—adult and pediatric—become long-term cancer survivors, it becomes ever more imperative to identify ways to prevent, or at least manage, long-term complications from the cancer and its treatment.

Just how to do that forms the cornerstone of the research conducted at the University of Alabama at Birmingham (UAB) School of Medicine through its Institute for Cancer Outcomes and Survivorship (ICOS). “We are interested in developing a strong base of researchers who are focused on studying cancer outcomes long-term and identifying the issues cancer survivors face,” said ICOS Director Smita Bhatia, M.D., MPH. “We are continually striving to improve the quality of life of cancer survivors.”

Diverse Group

A diverse group of researchers from UAB participates in ICOS, including epidemiologists, physician scientists, behavioral scientists, molecular biologists and nurse scientists. They come from numerous departments, including radiation oncology, medical and pediatric oncology, and surgical oncology. Within ICOS, they have access to a state-of-the-art infrastructure that supports outcomes research, thus facilitating the transitional research that is integral to the Institute’s mission.

“The overarching goal of the ICOS is to conduct cutting-edge research in cancer outcomes across the age spectrum,” Bhatia said.

Since its founding in 2015, Institute researchers have received more than $10 million in grants from the National Institutes of Health and private foundations, and published more than 250 papers in peer-reviewed journals, a third of them high-impact journals.

Asking the Right Questions

All research studies start with asking the questions that no one has asked before, Bhatia said. “Questions are definitely going to move the field forward and make people’s lives better,” she noted.

For instance, a current study is examining long-term morbidity in pediatric cancer survivors, 60 percent of whom will eventually develop complications related to their cancer treatment. “We are systematically studying the molecular basis of these long-term complications,” Bhatia said.

Questions include: Why does radiation increase the risk of other cancers? How does a child’s DNA make them more prone to radiation-related cancers? Are there ways to predict children who are more likely to develop  treatment-related conditions and find alternative treatments to attack their cancer?

The Institute is also studying adherence to oral chemotherapy. “We find that children with acute lymphoblastic leukemia (ALL) often don’t take their medications as directed,” increasing their risk of relapse, Bhatia said. “We are now testing strategies to improve adherence to oral chemotherapy.”

To explore the impact of radiation and chemotherapy on the developing brain, researchers are using MRI to identify cellular signs of “chemo brain” and looking for ways to protect the brain during treatment.

“When a new patient comes in with cancer, the first thing we have to do is get rid of that cancer,” Bhatia said. That typically means using agents known to increase the risk of neurocognitive deficits. “So we have to develop methods to reverse or halt these complications.”

Several other research questions are under investigation, including ways to:

  • Expand the HPV vaccination rates in childhood cancer survivors
  • Determine the burden of morbidity older cancer survivors experience
  • Understand the best way to treat older patients with cancer without causing undue toxicity
  • Improve end-of-life experiences for cancer patients


Understanding ICOS Research
Learn more about ICOS research and watch an interview with Smita Bhatia, M.D., MPH.

Hematology and Oncology

Developmental Therapeutics Offers Next Generation of Cancer Medicines

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One of the most devastating things a doctor has to do is inform a family that their child with cancer has run out of options. At Children’s of Alabama, however, clinicians often have one more thing to offer: access to early-stage clinical trials for potentially lifesaving drugs through its Developmental Therapeutics Program.

“Development therapeutics is about the next generation of medicines that will hopefully improve outcomes and reduce side effects for children with cancer,” Program Director Gregory Friedman, M.D., said.

Children’s is able to provide access to investigational compounds because it is one of just 21 pediatric oncology programs in the country invited to participate in the Children’s Oncology Group Phase 1 and Pilot Consortium. Consortium studies, Friedman said, “are how we’ve improved survival rates in recent years.”

Studies offered through the Developmental Therapeutics Program are generally Phase 1 or Phase 2 trials designed to demonstrate proof of concept, safety, tolerability and efficacy of new compounds. Currently, the program is managing more than 40 such studies.

Friedman is also developing a translational program to quickly move investigator-initiated research from laboratories at the University of Alabama at Birmingham (UAB) and Children’s into the clinical setting by providing an interface between the investigators and regulatory bodies, including the Food and Drug Administration. In addition, the Developmental Therapeutics team works with industry to develop new agents and is exploring participation in disease-specific pediatric consortiums.

Through the Developmental Therapeutics Program, Children’s also participates in the NCI-COG Pediatric MATCH trial, the largest precision medicine trial of its kind, in which tumor tissue is sent to the NCI for molecular testing to identify genetic abnormalities driving cancer growth. The goal is to then identify investigational or existing drugs to target those abnormalities and conduct clinical trials of the agents.

Friedman stresses that it takes a team to run the program including other physicians, a nurse manager, a clinical trial specialist, a data information coordinator and regulatory experts.

The goal, he said, is to continue to grow the program. “Our ultimate goal is to have a trial available for every child and family in these very difficult situations where few treatment options exist,” he said.

Viral Therapy in Malignant Brain Tumors Offers Hope

Developmental Therapeutics Program Director Gregory Friedman, M.D., is the principal investigator on one of the most exciting studies underway in pediatric cancer: evaluating the use of a cold sore virus to treat children with progressive malignant brain tumors. The approach is based on the finding that pediatric brain tumors are highly sensitive to genetically engineered oncolytic HSV-1 G207, which lacks genes essential for replication in the normal brain. The Phase 1 trial is designed to evaluate the safety, tolerability and preliminary efficacy of G207 delivered directly into the brain via intratumoral catheters.

Friedman and his team presented preliminary results on the treatments effects during the International Symposium of Pediatric Neuro-Oncology Meeting in Denver in June 2018. There were no dose-limiting toxicities or serious adverse events related to the virus and five of the six patients who received treatment demonstrated positive responses. One patient is now more than 21 months out from the treatment with a significant improvement in their well-being.

Since then, at least three other children have been treated safely with evidence of favorable drug activity. The next phase of the study will test the treatment’s safety in combination with a single dose of radiation, which is designed to enhance an immune response against the tumor.

Cancer Fighters
Learn more about the Alabama Center for Childhood Cancer and Blood Disorders. www.childrensal.org/cancer.

Hematology and Oncology

A Holistic Approach to Childhood Cancer Survivorship

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Significant improvements in pediatric cancer management means that an estimated 84 percent of children and adolescents diagnosed with cancer will become long-term survivors. However, while they may have overcome their original malignancy, they have a high risk of complications, including impaired growth, heart and lung problems, secondary cancers, learning disabilities and vision or hearing problems.

Yet, said Smita Bhatia, M.D., MPH, who directs the Institute for Cancer Outcomes and Survivorship at the University of Alabama at Birmingham (UAB) School of Medicine, “Research shows that primary care physicians are reluctant to take care of cancer survivors because these survivors have so many treatment-related complications. Often, these kids fall through the cracks.”

That’s where the Taking on Life After Cancer (TLC) survivorship program comes in. It focuses on improving the health and well-being of childhood cancer survivors and is the only clinic of its kind in Alabama.

“There is an increased need to provide care tailored to the long-term survivors of pediatric cancer,” said the program’s Medical Director Kimberly Whelan, M.D., MSPH. Not only are they at increased risk for numerous medical problems, she said, but they also often experience neurocognitive issues that can impact their schooling or job performance. “We strive to look at them holistically and see how they’re doing physically, emotionally and mentally, and give them the tools they need to succeed in life.”

When the clinic began in 2004, patients were seen just once starting two years after their last treatment. Today, patients are seen annually. “We learned that following them long term is important because the issues they face two to three years after treatment are different than the ones they may face five or 10 years after therapy,” Whelan said.

Wendy Landier, Ph.D., RN, CRNP, manages the clinical aspects of a patient’s visits. During the one-day visit, patients and their families see a physician or nurse practitioner who specializes in survivorship care, as well as a social worker to help with any issues related to costs and insurance. A neuropsychologist screens for problems with school or job performance. “The visit is tailored to meet the individual needs of each survivor,” she said. “For instance, educational materials are personalized so they address the specific treatment that each survivor received, as well as the potential complications that can arise as a result of that treatment.”

Patients also have the opportunity to participate in research studies designed to advance knowledge about survivorship issues. “We’re trying to learn more about why some survivors have certain complications and others don’t, and to develop mechanisms to reduce those complications,” Whelan said.

All visits are tailored to the individual child, their cancer and previous treatments. So a child who previously received radiation therapy to the chest, for instance, will undergo tests to assess lung and heart function. Other children may need their bone health checked regularly.

One task the clinic doesn’t do is screen patients for any recurrence of the original cancer, Whelan said. “So maintaining their relationship with their primary oncologist is important,” she said.

Patients are referred by their primary care physician or self-refer, Whelan said. Either way, the patients’ primary doctor receives summary reports. “We would love to partner more with the primary care physicians in the care of these patients,” she said.

The clinic currently follows about 500 patients, with another 100 added each year. All can be seen for the rest of their lives, regardless of age. “Our goal is to make sure they stay healthy,” Whelan said.

Dealing With a Cancer Diagnosis
Learn about Children’s of Alabama’s Hope and Cope Psychosocial Program.