Three Common Challenges—and Solutions—for Bone Marrow Transplant Success

CHOC’s Blueprint for Achieving Successful Outcomes for Bone Marrow Transplant Patients

Long-term survivorship and improved quality of life among pediatric cancer patients undergoing bone marrow transplants is routinely threatened by three common challenges that all pediatric oncologists face: cancer relapse, infection and graft versus host disease (GVHD). The oncology team at the Hyundai Cancer Institute at CHOC is overcoming these challenges — and delivering survival outcomes better than the national average.

“What we want for bone marrow transplant patients is for them to go through transplant without getting any infections; to have a small, controlled amount of GVHD; and for their cancer to never return and their immune systems to work fine,” says Dr. Rishikesh Chavan, pediatric oncologist at CHOC. “That would be the best-case scenario, and our team at CHOC is constantly optimizing to that.”

Dr. Chavan says this best-case scenario can be difficult to achieve because of common challenges associated with bone marrow transplants: infections, GVHD and relapse. CHOC is innovating better solutions to defeat these challenges:

  1. Preventing infections: CHOC has a robust program that covers infection prevention, infection surveillance, and timely and appropriate treatment of infections if they arise. “Post-transplant, families receive a dedicated callback number and prompt follow-up to answer their questions and triage them appropriately,” says Dr. Chavan. “If a complication occurs such as fever, patients are seen within 15 minutes of arriving to our ED and their first dose of antibiotics is administered within 60 minutes of their ED visit.” CHOC routinely monitors for infections and underlying immune status, including surveillance labs to check for viral and fungal infections. There is also a keen focus on ensuring all post-transplant patients are re-immunized to prevent infections. With the COVID-19 pandemic, telehealth checks are frequently held to see how the patient is doing and avoid unnecessary hospital visits.
  2. Preventing GVHD: “A little bit of GVHD is not bad, because it tells us the new immune system from the donor is functional and responding,” Dr. Chavan says. “In fact, patients who have Grade I GVHD have better long-term survival outcomes than patients who have no GVHD at all.” Based on the use of post-transplant cyclophosphamide, CHOC has been successful in preventing GVHD in most patients despite having more mismatched/haplo transplants. To manage more serious grades of GVHD, Dr. Chavan is starting a new clinical approach at CHOC dedicated to treating GVHD. “The clinic will utilize our tumor board team-based approach for quickly recognizing GVHD based on clinical as well as laboratory data and using that information to match patients to appropriate GVHD treatments,” he says. “This design will allow us to review what is working, what isn’t and switch treatments quickly, if needed, to help patients get better. Having this ability at our clinic to respond quickly and offer very personalized treatments is the future solution to managing GVHD.”
  3. Preventing relapse: Patients’ bone marrow is checked for engraftment studies and minimal residual disease after transplant through monthly marrows, which is essentially surveillance for relapse. If a patient is likely to relapse because they are at a higher risk of leukemia to begin with or based on their surveillance marrows, they receive donor lymphocyte infusions to support their immature immune system as well as other regimens to prevent or treat relapse. Dr. Chavan is also involved in research projects to study and mitigate potential factors that affect relapse in leukemia patients undergoing stem cell transplant and cellular therapy with a focus on regulatory T lymphocytes.

For proof that CHOC’s efforts in preventing GVHD, infections and relapse is working, bolstered by both algorithm-influenced care and a concierge-medicine approach, Dr. Chavan references patient survival outcomes from 2018 and 2019 in reports by the Center for International Blood & Marrow Transplant Research (CIBMTR). Results showed CHOC well above the national average for survival outcomes and higher than most of its cohort of transplant programs.

“A great team consists of a group of kind-hearted people who can not only detect and treat complications but also anticipate potential problems and try to prevent them, and that’s what we have here at CHOC,” Dr. Chavan says.

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the cancer specialty.

Learn how CHOC’s pediatric oncology treatments, expertise and support programs preserve childhood for children in Orange County, Calif., and beyond.

CHOC studies child maltreatment during COVID-19, adopts new tools to better recognize signs of abuse

With COVID-19 restrictions keeping more families at home, a critical question has emerged:

Are children suffering more physical and emotional maltreatment because they’re spending more time with parents who are dealing with extra stress in their lives?

A recently completed study by clinicians in the Julia and George Argyros Emergency Department at CHOC Hospital sheds some light on whether child abuse cases are rising because of stay-at-home orders. The study comes as CHOC ED personnel are using two new screening tools to help clinicians better recognize signs of abuse as well as victims of human sex trafficking.

COVID’s effect on child maltreatment

CHOC ED personnel studied whether the incidence of child maltreatment – which includes physical, sexual and emotional abuse, plus neglect – among patients being admitted to the emergency department has risen since the pandemic began in mid-March 2020.

They reviewed records of ED visits of patients up to 18 years old during a 3 ½-month period from March to July 2020 and reviewed the Child Protective Services database, then compared that period to the same time frame in 2019, 2018 and 2017.

Result: More reports of child mistreatment – 215 – were filed during the COVID-19 pandemic, compared to 204 during the same period in 2019, 199 in 2018 and 158 in 2017.

This is especially significant because CHOC’s ED has experienced a significantly lower ED patient census during the pandemic compared to pre-COVID days, says Dr. Mary Jane Piroutek, a CHOC ED attending physician.

Dr. Mary Jane Piroutek, CHOC ED attending physician

While sexual and physical abuse cases were down in the 3 ½-month period in 2020, cases of general neglect and medical neglect, as well as emotional abuse, were higher during COVID compared to the previous years.

Erika Jewell, manager of Case Management and Social Services at CHOC, put some of these numbers in context. In 2017, she reports, the rate of children in Orange County suffering abuse or neglect was 43.8 per 1,000, compared to 33.5 in 2012.

Of the 4,451 substantiated case of child abuse and neglect in Orange County in 2017, the vast majority – 3,204 – were cases of general neglect. Sexual abuse cases, in comparison, totaled 191.

“Our findings suggest the incidence of child neglect increased during the implementation of the stay-at-home guidelines,” says Dr. Piroutek, who spoke with Jewell and others on a panel on Research Day on Nov. 18, 2020.

Knowledge of such a trend, Dr. Piroutek explains, could help providers identify children at risk for maltreatment and, ultimately, provide an impetus to shape public policy and to improve the effectiveness with which resources are allocated to address the COVID-19 public health crisis.

Two new screening tools

Beginning in October 2019, the CHOC ED rolled out the first of two new screening tools aimed at making it easier for nurses and doctors to better identify patients at risk of abuse.

The first new screening tool being used in CHOC’s ED is TRAIN, for Timely Recognition of Abusive Injuries Collaborative. It is used to screen patients 6 months and younger.

The second screening tool, launched in July 2020, is CA-CDS, for Child Abuse – Clinical Decision Support. It is used to screen patients 11 years or younger. Components include a triage screen where nurses or doctors answer five questions, a pop-up computer alert that flags which patients may be at risk for physical abuse, a link to order sets and CHOC’s computerized suspected child abuse form.

With these two new tools, the CHOC ED estimates it can detect 50 percent more sentinel injuries than before. A sentinel injury is a seemingly trivial one that can be viewed as a “sentinel event” for much worse injuries in the future. Research shows that one-quarter of abused children had previous sentinel injuries.

The ED is collecting data through December 2021 to evaluate how well the new screening tools are helping healthcare workers detect cases of maltreatment, Dr. Piroutek says.

“It’s a more data-based and methodical approach; you have a computer that’s looking at data and flagging concerning patterns for you: ‘Hey, there’s something that might be abuse here,’” Dr. Piroutek explains.

The new screening tools will help CHOC better comply with treatment guidelines set forth by the American Academy of Pediatrics (AAP), Dr. Piroutek notes.

“CHOC is committed to research for the betterment of our patients and children,” Dr. Piroutek says. “With the implementation of these new screening tools I am confident we can provide the best care for our patients.”

Screening for human sex trafficking has also become an important part of CHOC nursing care.

Sheryl Riccardi, Emergency Department manager at CHOC, says a steering group of about 20 associates has been established to help healthcare workers better identify, intervene and advocate for these victims, many of whom are minors and most of whom come from the Unites States.

Santa Ana is the largest hub of human sex trafficking in the state, she notes. The ED has begun screening 12- to 18-year-olds – regardless of their chief complaint for possible further evaluation – if a child reports a complaint indicating a high risk of abuse, Riccardi says.

CHOC, she adds, recently became a partner with the Orange County Human Trafficking Task Force, a law enforcement-led coalition that is committed to combating all forms of human trafficking through the rescue and long-term support of victims, prosecution of offenders, training of fellow law enforcement professionals, community awareness and effective public/private partnerships.

According to Waymakers and the Salvation Army, in 2019 there were 415 identified victims of human trafficking in Orange County, with sex trafficking victims totaling 359. The other victims were trafficked for labor.

CHOC is determined to do what it can to find and help these victims.

“We’ve very passionate about this,” Riccardi says.

Learn more about how to identify child abuse.

I’m a pediatric neurosurgeon. Here’s why I’m excited about the technology at our fingertips.

By Dr. Suresh Magge, medical director of neurosurgery at CHOC, and co-medical director of the CHOC Neuroscience Institute

Even as a child, I was fascinated with science, and it was ultimately the concept of using science and technology to help people that drew me to medicine. Today, I’m more excited and optimistic than ever about our ability as clinicians to provide best-in-class treatment to the patients we have the privilege to care for – particularly in a minimally invasive way.

While every effort is made for nonsurgical intervention, neurosurgery can often be the answer to saving or improving a child’s life. At CHOC, we are committed to creating a personalized treatment plan for each child, based on his or her needs.

When surgery is necessary, we strive to perform minimally invasive surgery whenever possible for the myriad benefits it brings our patients. Minimally invasive neurosurgery offers a smaller incision, less pain, minimal blood loss, shorter time spent in the operating room, shorter recovery time, shorter hospital stays and hidden scarring.

There are a number of tools that we use to make surgery less invasive. For example, we can use a small camera, called an endoscope, to look inside the brain without having to make a large incision. In some surgeries, we can use a specialized robot, called a ROSA robot, to allow for precise placement of catheters or electrodes, and to operate on tiny areas of the brain.

Here are four surgeries I’m excited about as a pediatric neurosurgeon. In each surgery, the child is asleep and does not feel any pain during surgery. 

  1. Endoscopic surgery — This option for many types of brain surgery allows the neurosurgeon to identify and treat conditions deep within the brain. A tube-like instrument with a camera is inserted into the brain through a small incision in the skull. In some cases, we can insert the tube through the nose and avoid making any incisions in the skull. This allows the neurosurgeon to have a clear picture of the tumor. Then, we use specialized surgical instruments to remove the tumor or damaged area. When possible, we use this technique for brain tumors, hydrocephalus, arachnoid cysts, craniosynostosis and skull base surgery. In treating craniosynostosis, endoscopic surgery can replace larger and more invasive surgeries but still achieve excellent outcomes.
  2. Responsive neurostimulation (RNS therapy) —The RNS system is similar to a heart pacemaker. By monitoring brain waves, it can detect seizure activity and then the system can respond to stop the seizure. What simultaneously amazes me and comforts families about this piece of technology is that patients can’t feel the device once it’s programmed. They don’t feel pain or anything unusual. Studies show RNS therapy reduces seizures and improves quality of life for most people who have used it.
  3. Deep brain stimulation This surgical treatment can offer lasting relief for many children who experience abnormal movements. CHOC offers DBS surgery for children with movement disorders of all degrees, including very complex cases. We are one of the only centers in the world to use a multiple stage approach that allows us to better target the correct areas of the brain, without the need to wake a child during surgery. DBS surgery at CHOC involves the placement of electrodes in the brain and wires that connect to a stimulator device implanted in the chest. The device is like a pacemaker; it sends impulses to the electrodes that tell the brain to stop or minimize uncontrolled movements throughout the body. Our specialized team places up to 12 electrodes, when needed, to target different areas of the brain to attain a good outcome. Surgeries take place in a state-of-the-art operating room at CHOC, which includes the latest navigation system for safer, more precise procedures and the ROSA 3D-mapping robotic system that aids surgeons in locating the exact areas to operate.
  4. Laser Interstitial Thermal Therapy (LITT) – Also known as laser ablation, this emerging technology provides pediatric patients with epilepsy and other conditions a range of benefits more traditional procedures can’t match and offers a potential solution for brain tumors that are hard to reach with traditional surgery. Instead of doing a craniotomy where a large incision is made to open up the skull, the neurosurgeon first makes a small hole in the skull just a few millimeters in a diameter. Then, under MRI visualization, the neurosurgeon can precisely position the laser probe and deliver heat to the specific area, which destroys the abnormal tissue. Laser ablation is especially useful in patients with tumors or seizure-generating abnormalities deep within the brain. Precision is essential in implanting the catheter, which guides the laser, since it allows the neurosurgeons to limit the thermal energy delivered to the tumor area only. Most LITT is minimally invasive and requires a short time in the operating room, and patients are often able to go home the next day.

Throughout my career, I’ve been fortunate to see firsthand how neurosurgery has advanced tremendously over the years, particularly through research and innovation.

I’ve had the privilege of studying and providing care at a number of institutions – Harvard, the National Institutes of Health, the University of Pennsylvania, Boston Children’s Hospital, and Children’s National Hospital (Washington, DC) — before coming to CHOC. At each of these institutions, it’s evident that through innovative technology and minimally invasive surgery, we as neurosurgeons can alleviate suffering and have a significant impact on the lives of children.

As a team here at CHOC, we always ask ourselves, “What is the best thing we can do for each child in the least invasive method, with the least amount of pain?” and then we try to do it in the most compassionate way possible.

It’s an exciting time in medicine, in part thanks to advances in technology — especially the pieces of technology that allow us to provide these minimally invasive surgical options that make a true impact on children and their families.

For more information about the CHOC Neuroscience Institute, click here.

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Western Pediatric Urology Consortium (WPUC) Aims to Develop More Impactful and Meaningful Research in Pediatric Urology

The merging of clinical experience, surgical expertise and evidence-based practices is critical for obtaining the best outcomes for patients and their families. Guided by these criteria, CHOC established the Western Pediatric Urology Consortium (WPUC) to develop impactful and innovative research to benefit pediatric urology patients in the years ahead.

“Pediatric urology is a small community,” says Dr. Antoine “Tony” Khoury, chief of pediatric urology at CHOC. “Relatively speaking, the number of pediatric urology patients with complex anomalies is low, so it can be challenging to design studies robust enough to answer the important questions, the questions we need to answer to care for our patients in the best way possible.”

Dr. Antoine "Tony" Khoury
Dr. Antoine “Tony” Khoury, chief of pediatric urology at CHOC

In an effort to bring together the leading pediatric urology groups, Dr. Khoury initiated the development of the WPUC. “With a larger patient pool and our collective resources, our consortium can design collaborative studies that none of us could accomplish on our own, which we hope will ultimately improve diagnosis and treatment in pediatric urology,” Dr. Khoury says.

The WPUC currently has 15 centers involved in the consortium, including three centers in Canada and two in the eastern United States. There are several active studies WPUC is investigating, including:

  • The effect of the COVID-19 pandemic on testicular torsion, a urologic emergency requiring surgery. The WPUC is investigating whether delaying treatment for torsion during COVID-19 increased the risk of testicular loss.
  • Posterior urethral valves, a serious congenital condition seen in boys, frequently leads to renal failure requiring kidney transplant. Are the graft survival rates of boys with this condition equivalent to patients with other conditions that lead to kidney failure?
  • Hypospadias repair, a surgery that is both an art and a science. The WPUC is using artificial intelligence to study surgical reports across the consortium to better understand decision-making and improve surgical techniques.

“These are long-term studies we are working on today that we’re hoping will effect change for our patients in the future,” says Dr. Khoury.

Dr. Antoine "Tony" Khoury at CHOC
Dr. Khoury

When asked if the COVID-19 pandemic had any impact on the WPUC, Dr. Khoury says their first inaugural meeting, which was scheduled to be held In March of 2020, was cancelled. “We were anticipating an amazing turn-out for the meeting in Orange County, but fortunately we were able to successfully transition to online collaboration. We have had several productive virtual meetings since March, and we have since launched three stellar research studies.”

Dr. Khoury stresses how important the collaboration is between the centers in the WPUC when it comes to advancing pediatric urology care. “In pediatric urology, there are not enough large-scale studies, so it’s important to involve multiple centers so we can accumulate enough data to come up with meaningful results in a reasonable timeframe. If we only rely on one center, we’ll never gather enough data to determine the best treatments and how to make the most appropriate decisions for these children.”

Dr. Khoury believes the WPUC will lead to new avenues of research, which could assist in developing new treatment protocols. “My hope is that we will change academic pediatric urology through the collaboration of the WPUC,” Dr. Khoury says. “The work we’re doing as a group right now will improve urologic diagnosis, treatment and research for the next generation of pediatric urology patients.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the urology specialty.

Learn how CHOC’s urology care, ongoing treatment and surgical interventions preserve childhood for children in Orange County, Calif., and beyond.

Ophthalmology division chief’s innovative vision continues to yield international awards

During his nearly 20 years as a pediatric ophthalmologist, Dr. Rahul Bhola has performed thousands of surgeries to correct strabismus, a condition in which the eyes are misaligned and do not track together.

And after each procedure, he feels an immense sense of gratitude for being able to profoundly affect the lives of children who, by the critical age of around 5, stand the best chance for successful outcomes before their brains get used to living comfortably with eye misalignment.

“What drives me is the patients we treat,” says Dr. Bhola, division chief of CHOC’s Specialists Ophthalmology and an associate clinical professor at UC Irvine School of Medicine. “The biggest thing is early diagnosis and prompt management, and with these surgical procedures, I can see the results right away. What can be better than that?”

Already the recipient of numerous national and international awards, Dr. Bhola, who joined CHOC in July 2017, continues to break new ground.

Recently, a paper he presented at a global conference of the World Society of Paediatric Ophthalmology and Strabismus won top honors in the category of innovation and strabismus surgery.

During his presentation at the WSPOS’ World Wide Connect 2020, Dr. Bhola described a new approach to surgically correct strabismus in kids diagnosed with horizontal misalignment associated with minimal vertical misalignment.

Traditionally, most surgeons would surgically correct the horizontal misalignment and hope the vertical condition would work itself out. There’s a risk, Dr. Bhola explains, in surgically correcting for mild vertical misalignment. The procedure involves cutting off and repositioning a muscle in a different spot, which can result in an overcorrection – thus making things worse than better.

Dr. Bhola came up with the idea of performing what he calls graded marginal myotomy of inferior oblique. Instead of cutting and repositioning the muscle off the eyeball, he makes an incision to weaken the muscle avoiding the potential risks of overcorrection and by grading is able to adjust the amount of vertical strabismus correction.

“We use prisms to measure the degree of misalignment to better determine how much we need to weaken the muscle,” he explains.

Dr. Bhola says he’s performed the technique on some 60 patients with excellent results.

“It sounds very intuitive, it sounds very easy, but it had never been done before,” he says.

Dr. Bhola says the paper he presented at the conference is expected to be published soon in a major medical journal.

“This (surgery) will be a great addition to our armamentarium of strabismus surgery,” he says.

Fixing the problem in one procedure

Strabismus is prevalent in about 5-7 percent of the pediatric population, Dr. Bhola says. In most cases, the condition is the result of an abnormality of the neuromuscular control of eye movement. Many children who undergo surgery for strabismus need about two to three surgeries in their lifetime for the condition to be adequately corrected, he adds.

Not so with his recently developed procedure.

“That’s one of the beauties of this surgery,” says Dr. Bhola, explaining that he’s able to correct both horizontal and vertical misalignment in one procedure.

“The chances of achieving a good outcome is best with the first surgery,” Dr. Bhola says.” In my experience, it’s best to be aggressive and adequately correct both horizontal and vertical misalignment in order to get the best possible surgical outcome.”

When Dr. Bhola joined CHOC a little more than three years ago, he was tasked with developing CHOC’s Ophthalmology Division into a destination center in Orange County and beyond.

He’s well on his way.

In 2019, CHOC’s Ophthalmology Division saw 5,500 patients (equating to 8,000 patient visits) with a 90-percent-plus patient satisfaction rate, Dr. Bhola says.

“We’re seeing exponential growth,” adds Dr. Bhola, who plans to grow the division to five or so specialists over the next few years. Currently, the division has two.

After graduating from medical school in 1996 and completing his first Ophthalmology residency from University of Delhi, India, Dr. Bhola further pursued another residency in Ophthalmology in the US. He went on to do his Pediatric Ophthalmology fellowship from two prestigious ophthalmology training programs. He says he always wanted to be a pediatrician and later fell in love with ophthalmology, and being able to practice Ophthalmology at CHOC, a world class pediatric hospital, gave him the best of both worlds.

“This is something I’m passionate about,” he says.

To learn more about Ophthalmology at CHOC, click here.

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