illustration of a brain's neural activity

Debuting sonodynamic therapy with ALA to treat rare brain tumors

illustration of a brain's neural activity

Preclinical studies show that guided focused ultrasound and ALA can slow growth of gliomas and extend survival.

Children’s National Hospital is conducting a first-in-human study of aminolevulinic acid (ALA) sonodynamic therapy (SDT) for diffuse intrinsic pontine glioma (DIPG).

Preclinical studies led by experts at Children’s National have shown that SDT through MR guided focused ultrasound (MRgFUS) to activate protoporphyrin IX (PpIX), an ALA, can slow growth of gliomas and extend survival in animal models.

In a recently published technical communication in the Journal of Neuro-Oncology, the authors briefly detail the rationale and mechanism behind the use of SDT using ALA for DIPG, review criteria for patient inclusion, and describe the first patient selected for this clinical trial.

“Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain tumor that occurs in children between 2 and 9 years of age,” writes Hasan Syed, M.D., co-director of the Focused Ultrasound Program at Children’s National and lead author of the findings. “Despite standard therapy, prognosis remains poor with an average survival of 9–12 months after diagnosis.”

Future procedures will involve ascending drug and low-intensity focused ultrasound (LIFU) energy dose combinations with evaluations of pharmacokinetics and radiographic evidence of tumor physiological changes.

Dr. Catherine Bollard webinar screen grab

In the News: The challenges of pediatric clinical trials

Dr. Catherine Bollard webinar screen grab“Pediatric cancer is rare, when you compare it to other forms of cancer, especially adult solid tumors. Often pharma companies are not wanting to fund trials that are exclusively to support a pediatric cancer indication. This is a question that I get asked a lot: How to deal with the so-called ‘valley of death’? … You can successfully complete a phase 1/phase 2 trial, show a safety and efficacy signal, but then lack the funds to get FDA approval. Several of us in the field are looking at other strategies to fill this gap, like forming consortiums and using institutional support.”

Catherine Bollard, M.D., M.B.Ch.B, director of the Center for Cancer and Immunology Research, joined Nature to talk about clinical trials for children, including the significant challenges she and her colleagues face to ensure potentially successful treatments have the funding to make it through the approval process. Learn more about her thoughts on the current landscape for pediatric clinical trials and her work on CAR-T cell therapies in her webinar.

Clumps of sickle cell blocking a blood vessel

Neurocognitive and emotional factors predict hospital visits in children with SCD


Clumps of sickle cell blocking a blood vessel

Neurocognitive and emotional factors are predictors of visits children with SCD make to the hospital.

Many children with sickle cell disease (SCD) experience significant pain that often results in trips to the emergency department (ED) or hospitalization. Disease characteristics explain some – but not all – of the variability in pain-related healthcare utilization. In a new study published in Pediatric Blood & Cancer, experts examined the role of neurocognitive functioning and emotional factors in predicting future healthcare visits for pain up to three years later.

The big picture

In the 3-year study of 112 youth with SCD between ages 7-16, researchers found that poorer attentional control and greater emotional distress predicted more ED visits and hospitalizations for pain years later.

Past studies that have pointed to the importance of neurocognitive and emotional factors in the experience of pain have only looked at relationships at a single point in time.

“Those types of studies limit our ability to evaluate the directionality of relationships and consider the implications of neurocognitive functioning and emotional well-being for children’s health as they get older,” said lead author Steven Hardy, Ph.D., director of Psychology and Patient Care Services and psychologist in the Center for Cancer and Blood Disorders (CCBD) at Children’s  National Hospital.

Why it matters

This study advances the understanding of the effects of neurocognitive functioning and emotions on the course of pain and disease morbidity in pediatric SCD.

Additionally, the findings will benefit patients by shedding light on potential intervention targets to support effective pain management.

“It also helps to reframe the conversation around pain and healthcare utilization in SCD by broadening our understanding of the factors that precipitate pain to include neurocognitive functioning and mental health,” Dr. Hardy added.

What’s unique

This work demonstrates that factors beyond disease characteristics are important to consider in a comprehensive approach to managing pain and improving quality of life for children with SCD.

“It shows that we also need to be thinking about how neurocognitive functioning and mental health affect one’s ability to manage their disease in terms of taking medications, avoiding pain triggers, coping with pain, communicating about symptoms and advocating for needs,” Dr. Hardy said. “Future work will look to see if we can preserve neurocognitive functioning and support mental health as a way to reduce pain impairment and improve quality of life.”

Children’s National is conducting several studies focused on better understanding the course of neurocognitive functioning and pain in pediatric SCD. Psychologists in the CCBD are also exploring novel interventions to preserve neurocognitive functioning and promote the development of effective strategies for coping with pain in SCD.

Cancer cells

DOD $1.3M award will launch clinical trial to treat sarcoma

Cancer cells

MPNST is a type of cancer called a sarcoma.

The Department of Defense (DOD) awarded Children’s National Hospital $1.3M to launch a unique clinical trial. The trial will evaluate the safety of a novel drug for patients with a rare but aggressive cancer known as malignant peripheral nerve sheath tumors (MPNST).

MPNST is a type of cancer called a sarcoma. While rare in the general population, about half of all MPNST are diagnosed in people with Neurofibromatosis Type 1 (NF1), a condition characterized by changes in skin coloring.

“MPNST is a life-threatening cancer for which there are no adequate medical options,” said AeRang Kim, M.D., Ph.D., director of clinical research of the Division of Oncology at Children’s National. “With the support of this grant, we will conduct a clinical trial to identify effective agents that could be of great benefit to all patients with NF1 who are at risk for sarcoma.”

MPNST are aggressive and frequently metastasize. The tumors that are not able to be removed with surgery rapidly progress and become lethal. In people with NF1, MPNST often develops within benign tumors, especially atypical benign tumors.

The hold-up in the field

Scientists have been looking at the cell signaling process within both pre-cancerous tumors and cancerous MPNST. Previous research has shown that the MEK and MDM2 signaling pathway influence the development and growth of these tumors. By blocking this interplay, the Zhu Laboratory at Children’s National has demonstrated that tumors can get smaller when treated with drugs that inhibit MEK and MDM2 in pre-clinical models.

What’s unique

The trial is uniquely designed to evaluate target inhibition of novel drugs by looking at signals that may help in determining tumor response. This work will provide people with NF1 and MPNST potentially helpful treatments and increase the knowledge for all people with NF1 and those at risk of MPNST. The drugs will be available to all patients who enroll to the study.

First-of-its-kind holistic program for managing pain in sickle cell disease

The new sickle cell clinic prioritizes looking at the whole person and considering multiple factors that promote health.

The sickle cell team at Children’s National Hospital received a grant from the Founders Auxiliary Board to launch a first-of-its-kind, personalized holistic transformative program for the management of pain in sickle cell disease (SCD). The clinic uses an inter-disciplinary approach of hematology, psychology, psychiatry, anesthesiology/pain medicine, acupuncture, mindfulness, relaxation and aromatherapy services.

Focusing on the “whole person health,” this clinic prioritizes looking at the whole person — not as individual organs or body systems — and considering multiple factors that promote health. Strategies taught in the clinic allow patients to manage their pain effectively by improving self-efficacy, coping mechanisms, and encouraging use of non-opioid and non-pharmacological modalities for pain management. Below, Deepika Darbari, M.D., hematologist and lead of the clinic, and Andrew Campbell, M.D., director of the Comprehensive Sickle Cell Disease Program, tell us more about this unique clinic.

Q: What’s been the hold-up in the field to implement a clinic like this?

A: There are many barriers at different levels in establishing a clinic like this. Most commonly it is the lack of provider expertise, which may not be available at many institutions. Furthermore, services may be available but may not be covered by health insurance. Sometimes, access to these services may be difficult because of the limited locations where they may be offered and not in conjunction with a patient’s hematology care – like in our clinic – which adds to the burden for patients and their families.

Q: How does this work move the field forward in the space of SCD?

A: This clinic is a unique concept where patients and their families actively contribute to and are at the center of the management plan. The goal of this clinic is to provide holistic care to our patients and families and positively impact all aspects of their wellbeing.

Instead of treating a specific disease, “whole person health” focuses on restoring health, promoting resilience and preventing diseases across the patient’s lifespan.

This clinic will continue to provide traditional treatment options for management of SCD along with non-opioids and nonpharmacologic therapies for management of pain, which is the most common complication of SCD.

We are not aware of any such multidisciplinary clinic for SCD like ours at Children’s National. Our team has been invited to national and international scientific conferences to share our experience and educate other programs about how to establish and sustain a clinic like ours.

Q: How will this clinic benefit patients?

A: In SCD, the symptom of pain can start as early as in the first 6 months of life and continue to occur through the lifespan of a patient, often turning into a chronic pain condition. This chronic pain is very refractory to traditional treatments including strong medications like opioids, which may not provide relief while contributing to many side effects. Our goal for patients attending this clinic is to improve their pain experience without increasing side effects.

We hope that the approach offered in this clinic will allow us to decrease the incidence and burden of chronic pain in individuals living with SCD. We would like to offer these treatment strategies early in life, which may help reduce the burden of chronic pain in our patients. We also hope that patients who have developed chronic pain can utilize these strategies to manage their pain, enhance function, reduce opioid use and improve health-related quality of life.

Q: What are you most excited about?

A: We are very excited to build upon our previous work in this space. Our pilot program was started by members of our multidisciplinary team who volunteered their time and effort for this important work.

While providing care to our families and patients, we are also looking forward to collecting robust data that can demonstrate the impact of such an approach in reducing burden of pain in SCD. This data will be helpful in supporting future research and expansion of this approach to benefit all individuals living with SCD.


boy using spirometer

Hydroxyurea initiation improves spirometry results in children with sickle cell anemia

boy using spirometer

Hydroxyurea therapy may help preserve lung function over time in children with sickle cell anemia.

Children’s National researchers participated in a recent study suggesting that the use of hydroxyurea (HU) therapy in children with sickle cell anemia (SCA) may help preserve lung function over time.

Sickle cell disease is associated with various pulmonary complications, including reactive airways, acute chest syndrome (ACS), pulmonary fibrosis and pulmonary arterial hypertension, which can lead to increased morbidity and mortality. Lung function tends to decline over time in individuals with SCA, and a more irreversible restrictive pathology develops with age and increasing respiratory complications.

Hydroxyurea is a disease-modifying therapy that has been shown to lower the rates of several complications of SCD, such as ACS and painful vaso-occlusive crises. It also might help lessen the severity of airway hyperreactivity in children.

This study provides evidence that hydroxyurea therapy may have a positive impact on pulmonary function in children with SCA, which could be of interest to doctors treating this patient population. By slowing the decline in lung function, hydroxyurea therapy may help reduce the risk of pulmonary complications and improve the overall health outcomes of children with SCA.

You can read the full study, Spirometric Changes After Initiation of Hydroxyurea in Children With Sickle Cell Anemia, in the Journal of Pediatric Hematology/Oncology.

Authors on the study from Children’s National Hospital include Dinesh Pillai, M.D., Deepika Darbari, M.D., and Anastassios Koumbourlis, M.D., M.P.H.

MRI Room

Using high-intensity focused ultrasound to treat solid tumors

“I think high-intensity focused ultrasound is a really exciting technology that will allow for a different paradigm of how we think about treating solid tumors, both in a local and in a systemic way,” says AeRang Kim, M.D., oncologist at Children’s National Hospital. Dr. Kim explains high-intensity focused ultrasound (HIFU) and how she and her team have used this technology to treat pediatric solid tumors.

HIFU is energy that can be focused on any region of the body. It allows doctors to provide different types of energy in varying amounts, and it’s typically coupled with magnetic resonance imaging, which allows for precise, focused energy to specific areas with accuracy and temperature guidance.

Children’s National was one of the first pediatric centers to open a clinical trial for the treatment of pediatric solid tumors. Since then, we’ve opened several other clinical trials and combined them with targeted chemotherapy for the ablation of benign tumors and malignant solid tumors. We are one of the few institutions that have this study open and we are leading the clinical trials and coordinating them with other institutions across the country.

illustration of how LIFU works

Understanding the use of focused ultrasound in pediatrics

The fundamental principle of focused ultrasound (FUS) is almost analogous to using a magnifying glass to focus beams of sunlight on a single point. Experts at Children’s National Hospital are using FUS as an acoustic lens that uses multiple intersecting beams and targets — specifically deep within the brain — to treat brain tumors in pediatric patients.

Hasan Syed, M.D., co-director of the Focused Ultrasound Program at Children’s National, explains how two FUS methods are currently being used in two different trials — sonodynamic therapy and blood-brain barrier disruption — for the first time in pediatrics.

What is focused ultrasound?

FUS has diverse biological effects that can be categorized as thermal or mechanical: high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU).

The treatments: 5-ALA with sonodynamic therapy and microbubbles for blood-brain barrier disruption

The difference between 5-aminolevulinic acid (5-ALA) medication and microbubbles has to do with the mechanism of treatment.

Dr. Syed explains that 5-ALA is activated by the focused ultrasound. Once activated, the goal is that the drug leads to tumor cell death.

Microbubbles, however, are used specifically to open the blood-brain barrier with focused ultrasound. When that happens, medications — or in our case the chemotherapy agents we’re using in our clinical trial — will hopefully have a better effect on treating the patient and taking care of the tumor.

Children’s National has now treated a series of patients with sonodynamic therapy — or LIFU and 5-ALA. There haven’t been any adverse events — the first time in the world that something like this has happened.

“I think it’s very exciting, and it brings us hope for new treatment options,” Dr. Syed said. Children’s National continues to recruit patients for this trial.

illustration of diseased kidneys

The future of Wilms tumor therapies: Q&A with Jeffrey Dome, M.D., Ph.D.

illustration of diseased kidneys

Dr. Dome’s mission is to come up with other therapies to treat Wilms tumor.

Conducting Wilms tumor research has placed Children’s National Hospital as the leader in this space. Jeffrey Dome, M.D., Ph.D., talks about the future of Wilms tumor therapies and what excites him about being able to offer different treatment options to this group of patients.

Q: What’s next for Wilms tumor therapy treatments?

A: Something we’ve learned is that we’re reaching the maximum benefit that we can achieve with conventional chemotherapy and have hit a plateau with some of the high-risk Wilms tumors.

If you look at the history of Wilms tumor, we’ve ratcheted up the cure rate by adding more and more chemotherapy agents. We’re now at a point in which patients can’t tolerate having more toxic chemotherapy added to their regimen. Our mission is to come up with other therapies that work differently.

Q: What have you learned that can lead to new therapy options?

A: I was a co-investigator on a National Cancer Institute-funded project called the TARGET study, which entailed sequencing several hundred Wilms tumors to identify genetic mutations that could be druggable. While a wealth of knowledge was gained on the nature of the biology of Wilms tumor, only a minority of Wilms tumors have targetable mutations. We understand what the mutations are, but most are not mutations that lend themselves to drug therapy.

Therefore, we must think about other forms of therapy for Wilms tumor, such as immunotherapy. That’s where the work with the T cells targeting the WT1 protein Wilms tumor cells come into play.

Q: What do the new therapies look like?

A: I think the future of Wilms tumor therapy will be combining the classic chemotherapy and radiation therapy that we’ve used for many years but also adding another component for the patients with the highest risk of relapse, such as immunotherapy.

Up until now, the studies that we’ve conducted using immunotherapy have introduced this treatment very late as a last resort after everything else has failed. We have seen early signals of efficacy and if we can corroborate this in current studies, I believe the future will be to introduce immunotherapy earlier in the treatment course.

There has been success using immunotherapy in other pediatric solid tumors such as neuroblastoma. I believe the prospects for Wilms tumor are also exciting.


histological image of Wilms Tumor

Leading Wilms tumor research nationwide: Q&A with Jeffrey Dome, M.D., Ph.D.

histological image of Wilms Tumor

Children’s National has become a resource for patients and families with Wilms tumor.

During the past year, Children’s National Hospital saw nearly 100 patients with Wilms tumor and other less common kidney cancers of childhood, far more than most centers in the country. This is largely due to the reputation the hospital has established for specializing in these diseases. While most patients with Wilms tumor have excellent outcomes, a significant minority of children with kidney cancer do not fare well. Children’s National has become a resource for patients and families with these challenging cancers.

Behind this reputation is Jeffrey Dome, M.D., Ph.D., senior vice president of the Center for Cancer and Blood Disorders and division chief of Oncology at Children’s National, and the team of researchers he leads. For over a decade, he chaired the Children’s Oncology Group Renal Tumor Committee, an opportunity that gave him and his work great exposure.

Dr. Dome shares more on how Children’s National is leading in this space and what the future holds for new, exciting Wilms tumor treatment options.

Q: How is Children’s National leading in this space?

A: The good news is that for the most common type of childhood kidney cancer, Wilms tumor with “favorable histology,” the survival rate is more than 90%, which is an incredible success story. But approximately 25% of children and teens with other types of Wilms tumor and other kidney cancers do not fare as well. We specialize in kidney cancers that are harder to treat, such as anaplastic Wilms tumor, relapsed favorable histology Wilms tumor, bilateral Wilms tumor, clear cell sarcoma of the kidney, malignant rhabdoid tumor and renal cell carcinoma. Because we see a relatively large number of patients, we can draw on our prior experience and observations to recommend the best treatment options.

Q: What’s unique about this research?

A: We have several early-phase clinical trials that are of interest for children with relapsed kidney tumors. Some of these trials are part of research consortia, such as the National Cancer Institute-funded Pediatric Early Phase Clinical Trials Network (PEP-CTN). Other studies have been developed in-house at Children’s National, including a couple of studies using T cells to target pediatric solid tumors. The T cells that have been engineered by the Children’s National Cellular Therapy Laboratory are of particular interest for Wilms tumor because they target a protein called WT1, which is expressed in most Wilms tumors. In fact, WT1 was named after Wilms tumor. We have now had more than 25 patients with relapsed Wilms tumor come from around the country to participate in these studies. Based on early successes, we are continuing this line of research and trying to improve the technology in the current generation of studies.

illustration of cancer cell with target on it

Cancer Genetics Program growth: Q&A with Joyce Turner, M.S., C.G.C.

illustration of cancer cell with target on it

The Children’s National Cancer Genetics Program has witnessed a 57% increase in total number of patients seen in the past 4 years.

The Children’s National Cancer Genetics Program, established to identify individuals with a greater likelihood for certain types of cancer and provide early detection and treatment, has seen immense growth in the past few years. Joyce Turner, M.S., C.G.C., director of the Cancer Genetics Program, shares insights on the program and her vision for what’s next.

Q: How would you describe the recent growth of the program?

A: We’re extremely proud of the growth in the Cancer Genetics Program! Our program has witnessed a 57% increase in terms of the total number of patients seen (both new patients and patients seen for follow-up) in the past 4 years. A portion of this growth may be related to the COVID-19 pandemic as we were able to continue seeing patients in the comfort of their home. Our team has also expanded with the addition of a nurse coordinator in 2022.

Q: How does the work in this program benefit patients?

A: If we’re able to find a change, also known as a mutation, in a gene that explains a patient’s cancer diagnosis, we can support the care team with a better plan for how to screen the child moving forward. Since different genes can put patients at risk for specific types of cancers, knowing which gene mutation is present allows us to put a certain set of screening guidelines in place for long-term medical management.

Our goal with regular surveillance is to identify a tumor prior to becoming symptomatic when treatment is optimal for the patient and suffering is minimized. If we can identify a gene mutation in a patient, we can also test family members for the known gene change, so that they can benefit from screening as well if need be. After all, gene mutations can run in families. This also allows our team to share information with the patient’s family about the chance of recurrence in another child.

Q: What are you looking forward to in the future regarding advancements in the field of cancer genetics?

A: I am most looking forward to the newer technologies that will become the standard of care in the future.

Right now, we predominantly look at the ‘coding’ portions of our DNA, which are known as the exons. We are just beginning to learn about what lies within the introns, the genetic information between our exons, and we are finding that these regions are more important than we originally thought. RNA sequencing allows us to take a closer look at the effects of genetic changes within the introns. Right now, this technology is available on a limited basis from certain labs and for only a fraction of genes, but I see this becoming part of standard genetic testing in the near future.

Additionally, paired germline/somatic tumor testing (which looks for changes in cancer genes with which one is born and alterations in cancer genes within a tumor) has primarily been available in recent years on a research basis. However, the benefit of this technology is becoming more appreciated as it begins to move into mainstream practice. We have had to prove its feasibility and show that this type of testing can be performed in a timely manner. In doing so, this technology allows us to potentially determine the cause of a cancer, how to personalize one’s chemotherapeutic treatment based on molecular changes in the tumor and what we need to consider for screening purposes long-term. This type of genetic testing allows us to optimize overall patient treatment from the start. It’s an exciting time to be working in this field!

Dr. Yang of Children's National Research Institute

Unlocking treatments for neuroblastoma

Dr. Yang of Children's National Research Institute

Dr. Jianhua Yang talks about his latest research into neuroblastoma treatments at Children’s National Hospital.

Curing neuroblastomas is going to take years of investigation and persistence, and the team at the Center for Cancer and Immunology Research at Children’s National Hospital is laying the foundation for breakthroughs. Recently, Jianhua Yang, Ph.D., and his colleagues completed a study providing proof-of-concept, preclinical evidence for exploring ulixertinib as a novel pharmaceutical approach for targeting neuroblastomas.

The big picture

This inhibitor blocks a type of communication inside a cell called the extracellular signal-regulated kinases (ERK), which are believed to drive the growth of neuroblastomas and various cancers. In a study of preclinical models published in Cancers, ulixertinib strongly inhibited the proliferation of high-risk neuroblastoma cells inside and outside of living organisms. Investigators also found that ulixertinib sensitized the cancer cells for treatment with the conventional chemotherapy drug, doxorubicin. Yang and his colleagues hope that finding inhibitors like ulixertinib could someday unlock a modality for treating neuroblastomas.

What we hope to discover

“We are trying to figure out if we can find a novel target, which no one has studied,” Yang said. “Some kinases, over-expressed in neuroblastoma and medulloblastoma, are interesting in terms of their expression pattern. We want to learn how they can be activated and promote tumor growth, and then we can develop therapies to safely target that cellular change.”

Neuroblastoma is the most common pediatric extracranial tumor, accounting for 15% of childhood malignancy-related deaths. Although some lower-risk versions of the disease can be cured, high-risk neuroblastomas have proven invulnerable to treatments for decades.

Moving the field forward

Working multiple research tracks, Yang’s lab is also investigating antibody-based immunotherapy that could be used to block the growth of neuroblastomas. Combined with chemotherapies, he and others at Children’s National believe these potential therapies could change the way pediatric cancers are treated and improve the quality of life for survivors.

“It’s like a religion,” Yang said. “You have to believe in yourself. The chance to fail is high, but you have to believe. If we can develop one or two drugs before my retirement, that’s a huge success.”

Dalia Haydar

Harnessing children’s immune systems to fight their own brain tumors

Dalia Haydar, Pharm.D., Ph.D., principal investigator for the Program for Cell Enhancement and Technologies for Immunotherapies, recently joined Children’s National Hospital to help develop breakthrough treatments that hopefully will be a key in the fight against pediatric brain tumors. She brings her deep experience at St. Jude Children’s Research Hospital to the Center for Cancer and Immunology Research (CCIR) to help support the NexTGen team’s 10-year, $25-million Cancer Grand Challenges award.

Dalia – literally – has drive: She commutes 180 miles round trip from her home in Hershey, Pa., to her lab. She says she is grateful to be at one of the few research institutions in the world that is researching how to harness the power of CAR T-cell therapies to attack solid tumors in kids. While these therapies have been approved to treat leukemia and other blood cancers, solid tumors have proven far more stubborn. Haydar has tremendous hope that she and the team led by CCIR Director Catherine Bollard, M.D., M.B.Ch.B., will change that.

Q: Could you explain the importance of this research?

A: Unfortunately, once a patient is diagnosed with a brain tumor, especially a kid, there’s very little we can do. Using chemotherapy or radiation therapy has big disadvantages because of developmental delays and other side effects. We are hoping this kind of immunotherapy – where we take the patient’s own immune cells and engineer them in the lab to attack their cancer – will eradicate their very harsh and aggressive tumors, without causing significant adverse effects.

Q: How are researchers at Children’s National going to attack solid tumors with a treatment originally designed for blood cancers?

A: We have a lot of resources and expertise at Children’s National that we are trying to put together to develop a therapy that would cure brain tumors. Unfortunately, solid tumors are hard to treat and there are several challenges for any kind of immunotherapy. But right now, being at a place where all the necessary resources, support and expertise are available, we are hoping to address each of these challenges, and we are determined to do something in a meaningful timeframe to push that survival curve toward the advantage of those kids.

Q: How soon can this work be done?

A: Within two or three years, we are hopeful we’ll be able to identify the best working regimen of this CAR T-cell immunotherapy and investigate if it will work in a patient. I foresee, in the next 5 to 10 years, that we’re hopefully going to have such therapy for kids with brain tumors.

Q: What has surprised most you in your work?

A: There are so many challenges in developing immunotherapies for kids with brain tumors. First, if it works for adults, it doesn’t necessarily work for kids. Some of the tumors in kids are more aggressive. We need to understand the tumor itself, besides understanding the immunotherapy we’re developing.

The other challenge is CAR-T immunotherapy is not like a pill or taking radiotherapy that is standardized for several patients. It’s a very expensive therapy. It’s taking the patient’s own immune cell, like a bone marrow transplant. We put it in the lab, re-engineer the cells without transforming them into a cancer cell, enable those immune cells to attack the cancer, and then put them back into the patient. There are a lot of steps you need to take to make sure you don’t artificially harm those cells or introduce contamination.

One of the most intriguing challenges for me is how we make immunotherapy work for kids who have different kinds of brain tumors – a medulloblastoma versus a glioma versus an embryonal tumor. This is one of the challenges that keeps me on my toes, and I’m hoping to answer.

Q: What is the power of being in a multi-center environment like the Children’s National Research Institute?

A: We have to do enough science on the bench to support any proposal for the therapy to move to the clinic. The last thing we want to do is to investigate a drug or therapy in patients without really knowing how it works and the potential adverse effects. Being able to work with researchers at different stages of the bench-to-bedside spectrum, as well as being able to have access to patient samples and innovative preclinical models, helps push the science forward in a shorter time frame.

blood cells

Half-matched cells – not identical – can help patients live longer, study finds

blood cells

Severe aplastic anemia (SAA) is a rare but serious blood disorder. Children and adults with SAA get very sick with low blood counts, infections or bleeding.

A new study, published in The Lancet Haematology, finds that patients of all races and ethnicities can get successful transplants for severe aplastic anemia (SAA) through haploidentical, or half-matched, bone marrow transplantation (BMT).

The big picture

SAA is a rare but serious blood disorder. Children and adults with SAA get very sick with low blood counts, infections or bleeding.

Relapsed SAA is a marrow failure disorder with high morbidity and mortality. Although this is often treated with BMT at relapse post-immunosuppressive therapy, historically under-represented minorities often struggle finding a suitably matched donor.

“If SAA does not respond to the first choice of therapy or comes back after a period of health, then we call this relapsed and refractory SAA,” says Blachy J. Dávila Saldaña, M.D., Blood and Marrow Transplant Specialist at Children’s National Hospital and corresponding author of the study. “BMT is the only cure for relapsed and refractory SAA.”

Moving the field forward

Many diagnosed patients do not have a fully matched donor to have a successful BMT. However, the study’s findings show that a haploidentical BMT from a family member can help people live longer.

“This especially helps people who are American Indian or Alaska native, Asian, Black or African American, Native Hawaiian, other Pacific Islander, more than one race or Hispanic,” Dr. Dávila adds. “It’s easier for people in these communities to find a related half-matched than a fully matched unrelated BMT donor.”

The patient benefit

Haploidentical BMT will greatly expand the ability of experts to safely treat patients of non-Caucasian ancestry that suffer from this condition.

“The half-matched transplant is becoming more standard and as safe as those with a fully matched donor,” Dr. Dávila says.

Children’s National was one of a handful of pediatric hospitals in the United States to participate in this open trial. Our experts will now provide the framework to expand these services to pediatric patients across the world.

Abstract Happy 2022 New Year greeting card with light bulb

The best of 2022 from Innovation District

Abstract Happy 2022 New Year greeting card with light bulbA clinical trial testing a new drug to increase growth in children with short stature. The first ever high-intensity focused ultrasound procedure on a pediatric patient with neurofibromatosis. A low dose gene therapy vector that restores the ability of injured muscle fibers to repair. These were among the most popular articles we published on Innovation District in 2022. Read on for our full top 10 list.

1. Vosoritide shows promise for children with certain genetic growth disorders

Preliminary results from a phase II clinical trial at Children’s National Hospital showed that a new drug, vosoritide, can increase growth in children with certain growth disorders. This was the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature.
(2 min. read)

2. Children’s National uses HIFU to perform first ever non-invasive brain tumor procedure

Children’s National Hospital successfully performed the first ever high-intensity focused ultrasound (HIFU) non-invasive procedure on a pediatric patient with neurofibromatosis. This was the youngest patient to undergo HIFU treatment in the world.
(3 min. read)

3. Gene therapy offers potential long-term treatment for limb-girdle muscular dystrophy 2B

Using a single injection of a low dose gene therapy vector, researchers at Children’s National restored the ability of injured muscle fibers to repair in a way that reduced muscle degeneration and enhanced the functioning of the diseased muscle.
(3 min. read)

4. Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National, was selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children.
(4 min. read)

5. New telehealth command center redefines hospital care

Children’s National opened a new telehealth command center that uses cutting-edge technology to keep continuous watch over children with critical heart disease. The center offers improved collaborative communication to better help predict and prevent major events, like cardiac arrest.
(2 min. read)

6. Monika Goyal, M.D., recognized as the first endowed chair of Women in Science and Health

Children’s National named Monika Goyal, M.D., M.S.C.E., associate chief of Emergency Medicine, as the first endowed chair of Women in Science and Health (WISH) for her outstanding contributions in biomedical research.
(2 min. read)

7. Brain tumor team performs first ever LIFU procedure on pediatric DIPG patient

A team at Children’s National performed the first treatment with sonodynamic therapy utilizing low intensity focused ultrasound (LIFU) and 5-aminolevulinic acid (5-ALA) medication on a pediatric patient. The treatment was done noninvasively through an intact skull.
(3 min. read)

8. COVID-19’s impact on pregnant women and their babies

In an editorial, Roberta L. DeBiasi, M.D., M.S., provided a comprehensive review of what is known about the harmful effects of SARS-CoV-2 infection in pregnant women themselves, the effects on their newborns, the negative impact on the placenta and what still is unknown amid the rapidly evolving field.
(2 min. read)

9. Staged surgical hybrid strategy changes outcome for baby born with HLHS

Doctors at Children’s National used a staged, hybrid cardiac surgical strategy to care for a patient who was born with hypoplastic left heart syndrome (HLHS) at 28-weeks-old. Hybrid heart procedures blend traditional surgery and a minimally invasive interventional, or catheter-based, procedure.
(4 min. read)

10. 2022: Pediatric colorectal and pelvic reconstructive surgery today

In a review article in Seminars in Pediatric Surgery, Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National, discussed the history of pediatric colorectal and pelvic reconstructive surgery and described the key advances that have improved patients’ lives.
(11 min. read)

Jeffrey Dome

Jeffrey Dome, M.D.: Making strides in the fight against pediatric cancer

Jeffrey DomeJeffrey Dome, M.D., Ph.D., senior vice president of the Center for Cancer and Blood Disorders and chief of the Division of Oncology (ranked number 6 in the nation by U.S. News & World Report 2022-23 Best Children’s Hospitals annual rankings) at Children’s National Hospital in Washington, D.C., is an internationally recognized expert on pediatric solid tumors, with an emphasis on kidney tumors and sarcomas. He chaired the Children’s Oncology Group (COG) Renal Tumor Committee, which oversees clinical research on kidney tumors at more than 200 children’s hospitals around the world for more than 10 years. Dr. Dome is currently the Continental President of North America for the International Society of Paediatric Oncology (SIOP) and serves on several medical advisory boards for cancer centers and foundations.

“This is a remarkably exciting time to be in the field of pediatric oncology, with an explosion of knowledge on cancer biology and genetics and the availability of new treatment modalities including molecularly targeted therapy, immunotherapy and devices to improve drug delivery and local control,” says Dome. “I am proud of the multidisciplinary and cross-center collaborations at Children’s National to deliver the latest innovative therapies.”

The team at Children’s National is making strides across all programs to benefit patients with pediatric cancer. A few highlights include:

  • The Brain Tumor lnstitute is one of the most active clinical and translational research programs in the country. Collaborating with other leading institutions, the Brain Tumor Institute is supported by a robust brain tumor bench research program with focused laboratories in medulloblastoma, high-grade glioma, midline diffuse glioma, diffuse intrinsic pontine glioma, low-grade glioma and immunotherapy. The Brain Tumor Institute is leading two national studies, both funded through the Moon Shot lnitiative. In addition, it works closely with the Virginia Tech brain tumor laboratories on the new Children’s National Research & Innovation Campus.
  • Children’s National is the first children’s hospital in the United States with a Focused Ultrasound Program. This pediatric dedicated program includes high-intensity (HIFU) and low-intensity focused ultrasound (LIFU), offering minimally invasive surgical options for children with extra-cranial solid tumors, low-grade brain tumors and novel, potentially life-saving therapy with LIFU-mediated blood-brain barrier disruptions for diffuse intrinsic pontine gliomas.
  • Children’s National has developed multi-antigen specific T cells that have shown success in early phase clinical trials for leukemias, solid tumors and brain tumors. This promising area of research earned a major boost in the form of a $25 million dollar grant from Cancer Grand Challenges, founded in 2020 by Cancer Research UK and the National Cancer Institute in the U.S. This award supported the foundation of NexTGen, a team of scientists and clinicians with expertise in immunology, proteomics, mathematics and more, across eight institutions in the U.S., U.K. and France. The Center for Cancer and Immunology Research at Children’s National is one of the leaders of this effort.
  • The Blood and Marrow Transplantation team, one of the only dedicated pediatric bone marrow transplant programs in the greater Washington, D.C., region, is celebrating its 35th anniversary, with a history of clinical and research accomplishments for both malignant and non-malignant disorders. This program has seen tremendous success in their day 100 transplant-related mortality (TRM). Recently, for the first time, the day 100 TRM average was 0%, meaning that the program did not lose a patient due to transplant complications in the first 100 days – a remarkable achievement in the world of transplantation.
  • The Cancer Genetics Program has grown tremendously in the past few years, reflecting recognition that approximately 10% of childhood cancers have an underlying cancer predisposition. Despite COVID-19, during the past fiscal year, there were 282 patient visits which is a 40% increase from the prior year. The team has developed a collaboration with researchers in the Rare Disease Institute and now can offer studies for patients with Beckwith-Wiedemann syndrome, children with previously undiagnosed developmental delay and children with undiagnosed syndromes. Further, the team was awarded a grant from the Children’s Cancer Foundation to allow testing for those without insurance coverage.
Catherine Bollard

In the news: Novel research to stop pediatric brain tumors

“The team is really bringing in very new ideas from mathematical modeling, engineering, all the way to cell therapy, immunotherapy and immunology…This is what really excites and energizes us to be part of this great team, to address the Cancer Grand Challenge, to better target pediatric solid tumors.”

The Cancer Letter connected with Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, for a conversation about her work as a leader of the Cancer Grand Challenges NexTGen team. The $25 million effort is funded by Cancer Research U.K. and the National Institute of Health’s National Cancer Institute and the Mark Foundation for Cancer Research. Its ambitious goal: find novel therapies to break the stalemate in the treatment of pediatric solid brain tumors in the next 10 years. Bollard shared her work plan and the “secret sauce” that gives the team its edge with The Cancer Letter. Find out more about the hope behind this effort in the full interview here.

Catherine Bollard at People V. Cancer summit

In the news: People v. pediatric cancer

“I just want to hammer home the fact that, if you have a child with a pediatric solid tumor who relapses, most likely the chemotherapy that will be treating that child will be the same chemotherapy that a child diagnosed 20 years ago would have received. This is how little progress has been made…. This is what we are trying to change.”

Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National Hospital, pulled the curtain back on her work fighting pediatric brain tumors at The Atlantic’s People V. Cancer summit. This annual event brings together leading voices from the front lines for in-depth conversations about how to stop this complex and lethal disease. Dr. Bollard discussed the unique importance of collaboration among pediatric oncologists and the optimism she has for using a patient’s immune system to go after solid tumors with CAR T therapies.

pregnant woman at fertility consultant

Fertility preservation in sickle cell disease patients

pregnant woman at fertility consultant

Fertility is a long-standing concern for patients with sickle cell disease and their families.

In a recent review in the Journal of Clinical Medicine, researchers from Children’s National Hospital look at the current state of fertility preservation in patients with sickle cell disease and make recommendations for longitudinal post-treatment for these individuals.

Fertility is a long-standing concern for patients with sickle cell disease and their families. Current curative therapy for the disease requires gonadotoxic conditioning, which many patients resist because of the resulting risk of infertility. And, while standard fertility preserving interventions exist for pre- and postpubescent females and males, best practices for integrating these interventions into sickle cell disease care have not yet been established.

In their article, Children’s National hematologist Robert Sheppard Nickel, M.D., and co-authors review current fertility assessments, fertility considerations in pre- and post-transplant patients with sickle cell disease and fertility preserving interventions for patients. The authors conclude that in the future, less toxic curative approaches may make fertility preservation unnecessary, but at present, fertility preservation should be offered to patients with sickle cell disease pursing curative therapy.

Additional authors from Children’s National include Michael Hsieh, M.D., Ph.D., and Jacqueline Maher, M.D.

Read the full review article, Fertility after Curative Therapy for Sickle Cell Disease: a Comprehensive Review to Guide Care, in the Journal of Clinical Medicine.

stem cells

How our BMT program is excelling: Q&A with David Jacobsohn, M.D.

David Jacobsohn

Dr. Jacobsohn has led the BMT program at Children’s National as the division chief and talks about their incredible success over the last 5 years.

Over the last five years, the bone marrow transplant (BMT) program at Children’s National Hospital has continuously improved. From decreasing transplant-related mortality to 0%, to increasing the complexity of their transplants, the program continues to succeed in providing the best care to patients and their families.

David Jacobsohn, M.D., Blood and Marrow Transplantation division chief, offers insight on the goals the program has reached, the obstacles it has overcome and the vision for what’s next.

Q: How would you describe the success of the BMT program over the last 5 years?

A: We have progressively seen outcomes improve, marked by improvement in one-year overall survival of allogeneic transplants. Contributing to that is our outstanding day 100 transplant-related mortality (TRM). For the first time ever, the day 100 transplant-related mortality, averaged over allogeneic transplants done in the last 3 years, was 0%. That means that during that time, we have not lost a patient due to transplant complications in the first 100 days. This is a remarkable achievement in the world of transplantation.

Q: How does this work move the field forward?

A: We are particularly interested in continuing BMT in non-malignant conditions, such as beta-thalassemia, immunodeficiency and sickle cell anemia. We have one of the largest programs in the country for transplantation of patients with sickle cell anemia. We have been able to offer BMT to patients with sickle cell disease (SCD) and no prior complications, as a preventative procedure. Whereas in the past, it was mostly reserved for patients that had already been severely affected.

Q: How will this work benefit patients?

A: One of the key benefits that we’re seeing is that complications such as graft-versus-host disease (GVHD) have really decreased over the last few years based on the type of medications we’re using and procedures we’re doing.  Now most of our patients that are about six months out from transplant are off immunosuppression and are living relatively normal lives.

Q: What excites you most about this advancement?

A: We’re very excited about something called the Alpha/beta T cell depletion (A/B TCD) . We’re one of the few hospitals in the country offering this process.

This means we’re able to collect the donor stem cells and remove the T cells in the lab. Particularly the A/B T cells, which cause GVHD. We’re able to do this successfully not needing any medications to suppress the immune system. This is really quite novel. A lot of those medications have different side effects on organs, especially the kidneys. Now we can do transplants, even from half-matched donors, without immunosuppression.

We want to expand to more and more patients in the next three to five years so that no patients will need immunosuppression.

Q: What do you look forward to in the next couple of years?

A: In the next few years, we’re excited to venture more into cellular and gene therapy. With regards to cellular therapy, we’re offering something called CAR T cells to patients with acute leukemia. And it’s possible that this will actually replace transplant in some very high-risk leukemia patients.

We’re also looking forward to offering gene therapy to patient with SCD and beta-thalassemia.