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Neurology & Neurosurgery

Global Alliance Co-Founded by Children’s Neurosurgeon Affecting Change in Spina Bifida Prevention Effort

Spina bifida is the most frequently occurring permanently disabling birth defect to affect the nervous system.

Jeffrey Blount, M.D., MPH, knows the struggles of patients with spina bifida (SB). He and his colleagues in the Division of Pediatric Neurosurgery at Children’s of Alabama and the University of Alabama at Birmingham (UAB) have seen them firsthand—hydrocephalus, lower extremity paralysis, sleep apnea, pressure sores, variable incontinence, and the frequent need for multiple surgeries. Other doctors providing SB care see urologic, musculoskeletal, orthotic and ambulatory problems. A few years ago, the desire to address these issues led Blount to a big idea—one that would help not only his patients, but others around the world. In 2019, he co-founded the Global Alliance for the Prevention of Spina Bifida, or GAPSBiF, an organization dedicated to increasing awareness and advocating for the prevention of SB through large-scale food fortification with folic acid (FA). It’s already affecting change.

Blount is the medical director of the Pediatric Spina Bifida Clinic at Children’s of Alabama—one of the largest clinics of its kind in North America, following about 450 children. The medical professionals in the clinic work with those at the Adult Spina Bifida Clinic at UAB, which follows about 250 adults. In founding GAPSBiF, Blount partnered with Gail Rosseau, M.D., an international leader in global neurosurgery; Adrian Caceres, M.D., a Costa Rican neurosurgeon who accomplished widespread fortification of FA in Costa Rica; and Colombian neurosurgeon Kemel A. Ghotme, M.D., Ph.D., who had just completed a Ph.D. in Global Health Policy with a focus on FA fortification. One of the GAPSBiF’s major strategies for preventing SB was working with other neurosurgical and nutrition directed organizations in putting together a resolution that called upon all World Health Assembly (WHA) member states to embrace micronutrient fortification including FA to prevent SB. Resolution 76.19 was introduced by the Colombian government and 37 other member states and went through a rigorous process of vetting. In May, the WHA adopted it.

“This has real potential to favorably and fundamentally impact the global prevalence of SB and other micronutrient dependent diseases,” Blount said. “It is an essential step toward overcoming the stalled progress on the prevention of spina bifida.”

Spina bifida and folic acid

SB is the most frequently occurring permanently disabling birth defect to affect the nervous system. It results from the spine’s failure to close properly during the first month of pregnancy. The cause of SB is not fully understood, but it is thought to be associated with both genetic and environmental factors. The most important environmental factor is maternal intake of dietary FA, a B vitamin that is critically important in development and has long been known to reduce the risk of neural tube defects (NTDs), such as SB.

Nutritional shortage of FA in women of childbearing age is the most important contributor to SB prevalence worldwide. Many women supplement FA in their diet by taking 400 micrograms of FA while pregnant. But, in some cases, that’s not soon enough. “This problem of spina bifida occurs so early on in development that it has already occurred before most women even realize they’re pregnant,” Blount said. “So, it’s not like they can realize they’re pregnant, change their nutritional strategy and put up an effective barrier for this problem. Once they realize they’re pregnant, if they have the problem, it’s already occurred.” Fortifying widely consumed foods such as corn, grain or rice is more effective, which is why GAPSBiF works so hard to promote this strategy.

Evidence that fortification helps

In the U.S., mandatory fortification of enriched cereal grain products with FA was authorized in 1996 and fully implemented in 1998. Here, NTDs, including SB, affect approximately seven out of every 10,000 births. The rates in other regions that fortify are similar. In regions that don’t fortify, NTDs affect up to 150 births per 10,000.

But some countries—even advanced Western European nations—still are not practicing fortification, and, in many cases, are focused more on detection. But that approach can be problematic, Blount says. “Some places are very aggressive at terminating those pregnancies, which of course is a very difficult, very challenging, whole approach to problems. But it’s surprisingly widespread.”

GAPSBiF’s approach is centered around prevention. “Let’s keep these little children from getting this terribly difficult disease,” Blount said, “because it’s lifelong.”

The role of GAPSBiF

When Blount and his colleagues were forming GAPSBiF, they spoke with neurosurgeons from around the world. Even in North America, where fortification is already commonplace, SB takes an exhausting toll on patients, families, the health care system and the neurosurgical infrastructure. In many other countries, it’s much worse—due not only to the lack of fortification, but also because there are far fewer neurosurgeons per person. “A big part of their life and their world is taken up caring for these children,” Blount said. “And it prevents them from being able to do other things, such as taking care of people with strokes, taking care of people with trauma, things like that. So, it overloads an already challenged workforce.

“We saw this, we came together as a group, and we said, ‘Neurosurgery sees this. Neurosurgery knows this disease. We have a front-row seat to all these problems. So, why don’t we try to organize in such a way that we work with other agencies to try and attain this goal of universal fortification?’ ” Blount said.

“We know that if we can get folic acid into population food supplies, that up to 90% [of the SB cases worldwide] can be profoundly reduced,” Blount said. “Right now, the best studies suggest that we are collectively preventing less than one quarter of the global burden of SB.”

Fortification is not perfect, though. Blount emphasizes that while it can markedly reduce the prevalence rate of SB, it cannot completely eliminate the disease. That’s why he says that women and families who live in regions that fortify should not blame themselves for their child’s SB due to insufficient FA intake. “No woman should ever say to herself, ‘If only I had taken more folic acid, my child would not be affected,’ ” he said. Regulations for mandatory fortification of wheat flour with FA are currently in place in 60 countries, although in many cases, these regulations have not been implemented. Moving forward, Blount and his colleagues with GAPSBiF will remain active and invested in monitoring the resolution’s progress and working one-on-one with countries, guiding them in their national and regional implementation plans.

Neurology & Neurosurgery

Children’s Neurologist Helps Bring First Rett Syndrome Drug to Market

Children’s of Alabama pediatric neurologists Dr. Amitha Ananth (left) and Dr. Alan Percy

In March, the U.S. Food and Drug Administration approved the first treatment for Rett syndrome, a rare neurological disease. Considered a major breakthrough, the new drug, called trofinetide, or Daybue, may never have made it to market without the groundbreaking work of Children’s of Alabama pediatric neurologist Alan Percy, M.D.

Percy is one of the leading Rett syndrome experts in the world. He diagnosed the first patient with the disease in the U.S. and led a multicenter, National Institutes of Health-funded study on its natural history. He now co-leads, with Amitha Ananth, M.D., the Children’s of Alabama/University of Alabama at Birmingham (UAB) Child Neurology Rett Syndrome Clinic, one of the largest in the country and one of just 15 centers of excellence in Rett syndrome in the country.

“The availability of this medication is a game-changer in our efforts to treat this disorder directly, rather than only treating the specific problems that may arise,” Percy said. “It is remarkable that this treatment emerged less than 40 years after Rett syndrome first became known throughout the world.”

Rett syndrome affects about one in 10,000 babies, nearly all female. Infants with the condition develop normally until about 18 months of age, when they start missing developmental milestones and even regressing in some areas. The most classic feature, according to Ananth, a pediatric neurologist at Children’s, is loss of ability to use their hands in a meaningful way. Instead, they make repetitive, purposeless movements like handwringing, squeezing, clapping, tapping or rubbing. They also can’t communicate verbally.

Ananth has begun prescribing the new treatment to her patients. Prior to its approval, physicians prescribed physical, speech and occupational therapy; medications to treat symptoms like seizures and anxiety; and monitored growth and nutrition. “But there are a lot of aspects of this condition for which we really don’t have great drug treatment,” Ananth said. For instance, many patients with the disease will hold their breath or breathe very rapidly. “That can be quite disruptive to their daily life, but we don’t have great tools to deal with it.”

The Department of Defense initially developed trofinetide to treat traumatic brain injury. It’s a novel synthetic version of a tripeptide within the insulin-like growth factor 1 molecule (IGF-1). People with Rett syndrome have altered levels of IGF-1. Data suggests trofinetide helps brain neurons grow and communicate, while potentially reducing inflammation in the brain.

Children’s and UAB hosted clinical trials for the drug which involved 187 female patients with Rett syndrome ages 5 to 20. Those who received the drug demonstrated significant improvements on caregiver and physician assessments compared to those who received a placebo.

“To actually see a statistically significant difference between the two groups in just 12 weeks is pretty remarkable,” Ananth said. However, she stressed, “this isn’t a cure. But it is different from other medications we’ve been using because it targets the overall well-being of the person as opposed to specific symptoms.”

Anecdotally, Ananth has heard from parents of patients who received the drug that their daughters are more alert and engaged, both of which are important to the success of the various therapies the girls receive. For instance, some patients can be taught to use eye-gaze communication devices since most are nonverbal and can’t use their hands to communicate. “Parents said their daughters who received the drug were using [the devices] better,” she said. One girl who, prior to the trial, spoke only two or three words has now expanded her vocabulary exponentially, Ananth said.

The drug is a liquid administered by mouth or through a gastrostomy tube. The major side effects are vomiting and diarrhea, although clinicians are finding ways to reduce their severity and better manage them.

Another clinical trial is testing the drug in children ages 2 to 5. In addition, two companies have submitted applications to the FDA to start gene therapy trials, Ananth said, and one woman in Canada has received the first such treatment. Other investigational therapies are also under way. “We may very quickly move from an era with no treatments to one with multiple treatments and combination therapies,” she said. “It’s very exciting.”

Neurology & Neurosurgery

Children’s of Alabama neurologists launch SMA clinical trial opportunity

Dr. Michael Lopez is a co-investigator of a clinical trial involving a new drug for spinal muscular atrophy.

A new drug is in late-stage clinical trials at Children’s of Alabama for spinal muscular atrophy (SMA), a rare genetic disease marked by progressive muscle deterioration and atrophy. The drug, apitegromab, has a different mechanism of action than other SMA treatments and is being studied in patients already taking others.

Apitegromab is a human monoclonal antibody that targets the myostatin pathway, which affects muscle cell mass. “The thought is that if you can inhibit this pathway, then you could increase the muscle cell mass,” said Michael Lopez, M.D., Ph.D., co-investigator with Han Phan, M.D., at Children’s. Numerous animal studies show that inhibiting the myostatin pathway increases muscle mass, while overactivation reduces muscle mass.

Apitegromab binds to the precursor (pro/latent) myostatin, preventing its conversion into the active, mature form of the protein. This prevents the muscle cells from receiving the signals to reduce their mass. Because it works differently from the gene-based therapies already available, it’s being investigated as an adjunctive therapy, ideally providing another avenue to building muscle and reversing the weakness and atrophy SMA patients experience. “Muscle is regenerative; it can repair and renew itself,” Lopez said.

Apitegromab is the latest encouraging investigational drug in SMA treatment. In 2016, the FDA approved the first disease-modifying treatment for SMA, nusinersen, which works by increasing the amount of spinal motor neuron (SMN) protein produced by the SMN2 gene. SMA patients have nonfunctional SMN1 genes but several copies of SMN2 genes.

Since then, two other treatments, the gene therapy onasemnogene abeparvovec—which is administered just once to those less than 2 years of age—and the oral therapy, risdiplam—which also alters how effectively the SMN2 gene makes the SMN protein—have been approved.

In the latest clinical trial, called SAPPHIRE, participants must already be taking nusinersen or risdiplam. The trial will evaluate the drug in patients ages 2 to 12 who have SMA type 2 or 3 and can no longer walk. They will be randomized to receive one of two doses of apitegromab or placebo by IV infusion every 4 weeks for a year. Children’s is one of several participating centers in the U.S.

Previously, a phase 2 trial called TOPAZ showed improved motor function, even in patients who couldn’t walk. “The preliminary data was encouraging, but additional study is required,” Lopez said.

The progress that’s been made in SMA in the last few years, which Lopez called “revolutionary and game changing,” would not have been possible without the support of the families enrolling in clinical trials for the currently approved drugs, he said. “And they didn’t know if there would be a benefit, or even if they were in the investigational arm or placebo arm.” He also praised the Muscular Dystrophy Association Clinic at Children’s for the “superb care provided.”

“Every day, I’m in awe of the progress that has been made in treating this disease,” Lopez said. “We have gone from not having any treatment options at all and watching patients succumb to the disease to knowing that every patient now has a different life ahead of them—something that wasn’t imaginable when I started med school.”


Exploring the Link Between Childhood Adversity and Adult Heart Disease

Children’s of Alabama researchers are using an NIH grant to study the link between childhood adversity and adult heart disease.

Children’s of Alabama pediatric nephrologist Michael Seifert, M.D., and cardiorenal physiologist Jennifer Pollock, Ph.D., have received a five-year, National Institutes of Health-funded grant to explore the link between stressful childhood experiences and increased risk for cardiovascular disease in adulthood.

“We’re trying to study how exposure to early life stress (ELS) starts to have an effect in childhood on your cardiovascular system,” Seifert said. ELS includes adverse experiences such as physical and emotional abuse or neglect before age 18.

Studies over the last 20 years have linked ELS to adult-onset heart disease and other poor health outcomes like diabetes, mental illness, cancer and high-risk health behaviors. “But despite that, we still know relatively little about the mechanisms connecting the two,” Seifert said.

Seifert and Pollock will test their central hypothesis: ELS causes immune cell activation and inflammation, leading to vascular dysfunction and increasing the risk for hypertension and cardiovascular disease (CVD) later in life.

The investigators will follow a group of 300 adolescents from racially diverse backgrounds to identify critical clinical features and molecular pathways in ELS-associated CVD risk. Early research shows that this population has increased vascular stiffness and ambulatory diastolic blood pressure as well as pro-inflammatory metabolite and gene methylation patterns in plasma and circulating monocytes, respectively.

Seifert and Pollock will use comprehensive profiling to measure vascular stiffness and blood pressure and analyze the metabolome and epigenome—chemical signatures in blood and genes. The goal is to identify inflammatory and molecular pathways linked to cardiovascular changes. The grant also includes two basic science studies that will further inform the clinical trial and a similar study in young adults who had early-life stress exposure.

While it might seem counterintuitive to have nephrology specialists working on a cardiovascular health study, the two are closely linked. “We expect the same things increasing cardiovascular risk probably also increase chronic kidney disease risk,” Seifert said. “There is a lot of cross-talk between the cardiovascular system and the kidneys.” Findings may reveal new therapeutic targets. “This study has important translational potential,” Seifert said. “If we identify something in adolescence that’s driving this, maybe we can mitigate some effects of early-life stress.”


Initiative Aims to Reduce Fluid Overload in NICU Infants

A baby in a Neonatal Intensive Care Unit (Stock photo)

A new effort led by Children’s of Alabama pediatric nephrologist Lindsey Gordon, D.O., is taking aim at fluid overload and its harmful offshoots—including acute kidney injury, prolonged ventilation and hospital stays—in hopes of smoothing the path for infants in the NICU toward a healthier future. The initiative, dubbed CAN-U-P-LOTS, encapsulates a 10-step clinical practice bundle that will be tested over the coming year in collaboration with Children’s NICU clinicians.

Babies in the NICU face many grave health challenges, not least of which is fluid overload from IV medications and nutrition intended to keep them alive and help them thrive.

“New evidence shows how fluid overload in these neonates can cause a lot of problems in the long run, and many times, this can lead to a poor outcome,” Gordon, a third year fellow at Children’s and the University of Alabama at Birmingham (UAB), explained. “We’re trying to recognize the problem early to prevent some of these negative outcomes.”

Elements of the CAN-U-P-LOTS practice bundle include:

  • C: Evaluating the cause of fluid overload
  • A: Assessing albumin level and replenishing as needed
  • N: Limiting nephrotoxic medications that can hurt the kidneys
  • U: Assessing and treating high levels of uric acid and using dialysis for ultra-filtration to remove extra fluid
  • P: Perfusion to the kidneys by increasing blood pressure to ensure adequate blood flow
  • L: Lasix stress test and attempting diuretic use to assess if the kidneys respond
  • O: Monitoring urine output/obstruction carefully and considering placing a Foley catheter or doing a renal ultrasound to ensure no blockage
  • T: Monitoring total fluid intake with an eye toward reducing fluid amounts without sacrificing nutrition
  • S: Considering steroid use if a patient is on several vasopressors to further support blood pressure

Some NICU neonates have risk factors that confer a high risk for fluid imbalance, including patients:

  • with sepsis or acute kidney injury
  • receiving multiple antibiotics
  • being prepared for major surgery
  • requiring blood pressure support with multiple medications

“Preliminary data suggest that the vast majority of neonates admitted to the Children’s of Alabama NICU meet the criteria at least once for fluid overload problems,” Gordon said.

The CAN-U-P-LOTS effort “will produce valuable data that will help us understand whether and how this practice bundle can be implemented on a widespread basis,” said David Askenazi, M.D., director of the Children’s Pediatric and Infant Center for Acute Nephrology (PICAN).

“The idea started with a collaborative approach to help standardize care of these children and educate providers in an effort to equip the NICU team with these systematic tools, so babies don’t ever have to develop fluid overload—the soggy lungs or wet heart that will keep them sicker longer,” Askenazi said. “It takes a village because a project like this takes multiple people, conversations and opportunities to learn from one another.”

“Our hunch is it’s going to work,” he added. “If we can show clinical improvements in these vulnerable babies, we can communicate this to our colleagues to help babies around the country and world. We’re giving them 10 things to think about that can help them maximize medical management before these babies need dialysis.”


Interventional Pulmonology Now More Common for Kids

New technology is enabling Children’s of Alabama pulmonologists to offer more interventional procedures.

In his career as a pediatric pulmonologist at Children’s of Alabama, Ryne Simpson, M.D., has typically cared for children with conditions such as cystic fibrosis, prematurity and asthma. But as more children born with premature lungs survive and require tracheostomies and ventilators at home, “the flavor of the field has changed a bit,” Simpson said, “and interventional pulmonology is becoming more prevalent in pediatrics.” That’s why earlier this year Children’s began using new technology to offer more interventional procedures to its patients.

Interventional pulmonology is a subspecialty of pulmonary medicine dealing with minimally invasive, advanced bronchoscopic procedures, an example being removal of foreign bodies or other non-native material. Previously, that required surgery or a referral to an otolaryngologist, but both strategies have limitations. “Pulmonologists receive specific training in pediatric lung disease, which a surgeon or ENT physician may not always have,” Simpson said. With specialized equipment, “it can be a better situation for the patient.”

Historically, that equipment has been better suited for use in adults, and adult pulmonologists perform many more interventional procedures than pediatric pulmonologists. Thanks to the development of smaller tools and equipment, Children’s of Alabama can now offer certain interventional procedures to its patients.

One example is flexible bronchoscopic cryotherapy, something previously offered only in the adult setting. Children’s began using it in February 2023. It involves performing a bronchoscopy, then using a special probe to freeze a foreign body, piece of tissue or blood clot and pull it out for examination. “Previously, it could take hours because we often wouldn’t get the whole thing at once,” Simpson said. “Now we’re able to complete these procedures in significantly less time, which has been pretty amazing for the patients.”

Children’s also is working closely with the adult interventional pulmonology program at the University of Alabama at Birmingham (UAB), which has even more sophisticated equipment—such as robotic bronchoscopy—that in some cases is small enough to be used in the pediatric setting.

“It’s been a nice marriage between adult pulmonology at UAB and pediatric pulmonology at Children’s,” Simpson said. The pediatric department has been able to borrow certain equipment or, if needed, send children to UAB pulmonologists for help. “Sort of like: ‘You have the equipment, we have the knowledge, we can work together to get something done that previously we would have never been able to do,’” he said.


Study Aims to Standardize Kidney Stone Treatment

Cases of kidney stones are on the rise among children.

As the incidence of pediatric kidney stones rises, Children’s of Alabama is joining forces with the Pediatric KIDney Stone Care Improvement Network (PKIDS) to gain knowledge on patient-centered outcomes and comparative effectiveness data on kidney stone treatment and surgery to improve outcomes that are most important to patients.

PKIDS is a collaborative community of patients, caregivers, clinicians and researchers from 26 pediatric health care systems in the U.S. Through a prospective cohort study, the network is comparing stone clearance, re-treatment and unplanned health care encounters in children who receive surgical interventions as part of their clinical care. The goal is to enroll 1,300 patients throughout the country. “This is by far the largest pediatric stone study that’s been published to date,” Children’s pediatric urologist Carmen Tong, D.O., said.

Children’s is particularly well suited to participate in this study given that Alabama sits in what’s known as the “stone belt” for its higher incidence and prevalence of kidney stones. “It’s a pretty big economic and public health burden,” Tong said.

“There have not been any good studies looking at care for children with kidney stones, including patient and parent experiences with children needing kidney stone surgery,” Tong said. “Then there are issues with access to care, compliance with follow-up care and prevention of kidney stones. While these issues have been well studied in adults, our understanding in children is limited.” In fact, current guidelines for managing pediatric kidney stones are minimal and dated, she said. “This study is supposed to help change the paradigm and come up with a uniform, standardized algorithm on treatment of kidney stones.”

It’s not clear what’s driving the increased prevalence of stones in children, Tong said. Causes could be dietary (e.g., sugary drinks, high sodium) and/or hereditary, but climate change could also be a culprit, she said. “There are studies looking at weather-related causes. In the summer, when it’s hotter and children drink less water, the incidence rises.” Certain medications, like antibiotics, also increase the risk. Children are 50% more likely than adults to have recurrence within three years.

Families in the study complete a series of surveys about their and their child’s experiences with kidney stones and surgery. “We want to get from the parent and patient standpoint how they’re dealing with their kidney stones,” Tong said. On the clinical side, investigators will get a comprehensive view of how stones are treated around the country, including which surgical interventions were used and when.


Developmental Research Program Making a Difference for Multiple Specialties

Dr. Namasivayam Ambalavanan looks through a microscope in a lab at UAB. Ambalavanan leads the TReNDD research program at Children’s.

Much research in pediatrics focuses on disorders related to specific organ systems such as the brain, liver or kidneys, without an emphasis on the developmental time period that influences how those disorders may unfold in babies and young children. But a 15-year-old program at Children’s of Alabama bridges that gap, connecting investigators from a bevy of disciplines and supporting basic and translational research efforts that have paid off in better outcomes for patients.

Established in 2008, the Translational Research in Normal and Disordered Development (TReNDD) program is run by the Division of Neonatal Research. Namasivayam Ambalavanan, M.D., has been at the helm since its inception, directing TReNDD and neonatal research as well as co-directing the Division of Neonatology at Children’s.

“Our focus is on normal and abnormal development from late fetal life through early childhood—not so much on one disease or organ system, but the entire time period,” Ambalavanan said. “Ours is a highly collaborative network, bringing together people interested in disorders that occur during this time period. It’s relevant to all pediatrics, rather than one subspecialty.”

Faculty members from pediatric specialties such as neonatology, nephrology, pulmonology and critical care participate in TReNDD and typically approach the program with a certain research priority in mind, Ambalavanan explained. Ongoing basic science and clinical research projects, for example, are examining a wide variety of problems affecting neonates and other infants, from ventilator-induced lung injury to acute kidney injury to vitamin D supplementation in preterm babies.

Investigators can also rely on TReNDD facilities to help advance these projects, including core facilities able to run a wide variety of assays and a repository of pediatric biospecimens and model systems.

“Investigators come in with an area of interest, and we help them develop an animal model or assay to meet that interest,” Ambalavanan said. “We also put them in touch with additional people who can help, whether here or off campus.”

Over its history, the TReNDD program has produced research breakthroughs that have benefited children far and wide. Evaluating multiple signaling pathways during lung development, for example, led to key insights about lung impairments in preterm infants and tests determining who’s most vulnerable to certain breathing problems from their first day of life. Other lung research on the microbiome of tracheal aspirates of preterm babies led to the development of probiotics that can benefit lung health.

“I think TReNDD has a vital role because there are many people who want to do pediatric research but don’t know how to get started,” said Ambalavanan. “We’re a way of enabling people to both get their research done and find mentorship in research in the Department of Pediatrics.”

Hematology and Oncology

Increasing HPV Vaccination Rates in Young Cancer Survivors

A Children’s of Alabama researcher is working to improve HPV vaccination rates among childhood cancer survivors.

Childhood cancer survivors are significantly less likely to receive the HPV vaccine than their peers without cancer, despite having a three times higher risk of developing HPV-related cancers later in life[1]. A new initiative at Children’s of Alabama aims to improve vaccination rates, so patients can be protected long into their survivorship.

According to an HPV vaccine study led by Wendy Landier, Ph.D., CRNP, uptake among childhood cancer survivors was only about 24% compared to more than 50% in the general population. Although it’s not clear why young cancer survivors are more at risk for HPV-related cancers, it is likely due to effects from radiation and chemotherapy.

“One major reason for low vaccine uptake is that cancer survivors often don’t get a recommendation from their healthcare provider to receive the vaccine,” said Landier, the deputy director of the Institute for Cancer Outcomes and Survivorship at Children’s and the University of Alabama at Birmingham (UAB). Without that recommendation, there is a tenfold higher risk the young cancer survivor will not get the vaccine. This could be due to gaps in follow-up care after cancer treatment, Landier said, when preventive health measures such as vaccination may be overlooked. “When a child has cancer, they are often followed in their cancer center or in their pediatric hematology oncology center for many years beyond their treatment,” she said. “Sometimes the focus of that follow-up care is on the disease and not prevention.”

The vaccine, which helps prevent cervical, anal, penile and throat cancers, is recommended for everyone ages 9 to 26, and should be considered for people up to age 45. But, Landier said, primary care providers may also be uncertain about whether it’s OK to vaccinate these children. Landier and her team showed the vaccine is safe and provides a similar level of protection against HPV in pediatric cancer survivors when compared with people of similar age in the general population.[2]

Their study also showed, however, that the main reasons cancer survivors and their parents refused to participate in the trial testing the safety and efficacy of the vaccine were health beliefs and family decisions—for example, some had already decided that the child would not receive the HPV vaccine. Vaccine-related information deficits can influence vaccine refusals. For example, some parents or patients may not understand that males can benefit from the vaccine or that it should be given before a person becomes sexually active.[3]

To improve vaccination rates in pediatric cancer survivors, Landier is currently leading a study to test an intervention called HPV PROTECT.[4] The goal is to educate pediatric oncology providers on the importance of recommending the vaccine. The intervention focuses on communication training and tools to facilitate vaccine access. Investigators then monitor the vaccination rates in the clinic and let the providers know how they’re doing.

Early results are promising, Landier said, with pediatric oncology providers showing enthusiasm for the intervention. The intervention shouldn’t be limited to pediatric oncologists, however. “It can benefit all pediatric providers,” she said.

“Vaccines are such an incredibly important tool in helping our survivors to stay healthy across the lifespan,” Landier said. “And we certainly hope in the future there’ll be other vaccines to even prevent the original cancers.”

[1] Klosky JL, Hudson MM, Chen Y, Connelly JA, Wasilewski-Masker K, Sun CL, Francisco L, Gustafson L, Russell KM, Sabbatini G, Flynn JS, York JM, Giuliano AR, Robison LL, Wong FL, Bhatia S, Landier W. Human Papillomavirus Vaccination Rates in Young Cancer Survivors. J Clin Oncol. 2017 Nov 1;35(31):3582-90. Epub 20170824. doi: 10.1200/jco.2017.74.1843. PubMed PMID: 28837404; PMCID: PMC5662846.

[2] Landier W, Bhatia S, Wong FL, et al. Immunogenicity and safety of the human papillomavirus vaccine in young survivors of cancer in the USA: a single-arm, open-label, phase 2, non-inferiority trial. Lancet Child Adolesc Health. 2022;6(1):38-48. doi:10.1016/S2352-4642(21)00278-9

[3] Cherven B, Klosky JL, Keith KE, Hudson MM, Bhatia S, Landier W. Reasons for refusal of the human papillomavirus vaccine among young cancer survivors. Cancer. 2023;129(4):614-623. doi:10.1002/cncr.34521

[4] Landier W, Bhatia S, Richman JS, et al. Implementation of a provider-focused intervention for maximizing human papillomavirus (HPV) vaccine uptake in young cancer survivors receiving follow-up care in pediatric oncology practices: protocol for a cluster-randomized trial of the HPV PROTECT intervention. BMC Pediatr. 2022;22(1):541. doi:10.1186/s12887-022-03562-1

Hematology and Oncology

At the Intersection of Sickle Cell Disease and Asthma

A child uses an inhaler. (Stock photo)

While many people know of sickle cell disease (SCD), it may be surprising to learn that there is a high prevalence of co-occurring asthma among children with SCD. Brandi Pernell, DNP, has been researching social determinants of health that impact young patients with a double diagnosis.

“While I was pursuing different strategies for improvements among the asthma population, I discovered a connection between environmental stress and asthma,” said Pernell, an assistant professor in hematology and oncology at Children’s of Alabama and the University of Alabama at Birmingham (UAB). “When you look at the general population in comparison to the sickle cell population, you’re going to see that more children with sickle cell have a diagnosis of asthma because these two conditions have some overlapping inflammatory physiological pathways. That in itself is going to increase the risk of having asthma along with sickle cell.”

Asthma affects oxygen levels, especially among those who are undiagnosed or who are diagnosed but whose disease isn’t fully managed, Pernell said. And low oxygen is a risk factor for red-cell sickling. Patients with both asthma and SCD experience higher rates of pain and acute stress as a result.

Pernell estimates that she provides clinical care for 80 to 90% of young patients in the area who have both SCD and asthma, as well as any patient hospitalized with acute chest syndrome, an acute lung complication. “I have an acute care follow-up clinic where I see anybody who has been hospitalized with acute chest syndrome within four weeks of discharge to make sure that they have focused sickle cell management and any asthma management that needs to take place to reduce the risk of it happening again,” she said.

Another major component of care, Pernell believes, is patient education. She works with community-based organizations and the Sickle Cell Disease Foundation to provide health education. She also gives patients and their families handouts with up-to-date information for disease management. “I try to employ a multimodal approach to education, but I think that the best method is still face-to-face interaction,” she said. “After all the clinical care is done, I take time to see if there are any questions from patients. I explain why I’m recommending this therapy or why this therapy is so important and how it works exactly in your body—because I think that improves adherence if you understand why you need it—or what can happen if you don’t take a medicine or how it could further impact your health in a negative way.”

Support for her patients is also multi-modal. Pernell relies on assistance from a social worker who can lock in community services as needed. She also works with the Children’s of Alabama school liaison to ensure patients have comprehensive support. “By school age, about 30% of children with sickle cell will have suffered a silent stroke, which can impact the child neurocognitively and lead to a decline in academic performance,” Pernell said. She and the liaison also make sure that each patient has a 504 plan in place for important classroom accommodations, such as being able to maintain hydration and avoid temperature extremes to avoid a sickle cell crisis.

The research Pernell has undertaken looks closely at social determinants of health and those factors within a patient’s control that can improve symptoms. “We are focusing on lifestyle interventions,” she said. “Are there dietary changes (that can reduce symptoms?) Are there different stress reduction tactics that can be taken or things prenatally that moms can do?”

These and other research questions are also guided by input from the patients themselves. Pernell believes that patients, as the ultimate end users of any research discoveries, must be invested in the research planning process and study design. “We need to make sure that the outcomes that we’re pursuing are the outcomes that the patients themselves care about.”