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.

Recent Advancements Shape the Future of Sarcoma Care

The rarity of sarcomas and their large number of diverse histologies have made this group of cancers very challenging to manage. At the Hyundai Cancer Institute at CHOC, collaborative research, experimental treatment protocols and surgical advancements are setting the stage to change that.

“The sarcoma and solid tumor field hasn’t advanced much in the last 50 to 60 years, unfortunately,” says Dr. Elyssa Rubin, pediatric oncologist at CHOC. “But we’re making exciting progress that will hopefully improve the care pediatric patients with bone and soft tissue sarcomas receive in the future.”

Dr. Elyssa Rubin, pediatric oncologist at CHOC

As a member of the Children’s Oncology Group (COG), CHOC is involved in a number of clinical trials that seek to improve the outcome for children with cancer. The international collaboration allows for the compilation of larger data sets that can be used to improve both research and treatments.

“Currently, we are working with COG to harmonize all the clinical trial research from the last 50 to 60 years and creating common data dictionaries so we’re all speaking the same language and being consistent with our methods,” says Dr. Rubin. “Sharing data and having this larger database gives us a better understanding of what’s working, what isn’t and what to target with our treatments. Our ultimate goal is to have our collective data in one central location so we can work together and hopefully, make more advances. This collaboration is what’s needed if we’re really going to make progress.”

Besides her role as principal investigator in clinical trials, Dr. Rubin is researching an experimental maintenance therapy protocol for sarcoma patients.

“I’ve been fascinated by applying the advancements made in leukemia treatment to my sarcoma patients,” Dr. Rubin says. “Leukemia patients are treated with aggressive therapy upfront and then they go into a maintenance phase where they’re taking their medicine over an extended period of time. Over the last seven or eight years, I’ve used a similar approach with my high-risk sarcoma patients, which isn’t the standard of care. The encouraging trend I’ve noticed is a change in the pattern of their relapse and a longer extension of time until they relapse, which tells me this protocol is working to keep their disease under control.”

While it’s still early and more research is needed, Dr. Rubin says her protocol is picking up interest within the bone and tumor committee, and larger studies will be conducted that will have patients follow this protocol for at least six months.

As Dr. Rubin continues her research and the further investigation of her maintenance therapy protocol, other advances are being utilized at CHOC today, particularly in surgical technologies for the treatment of bone and soft tissue sarcomas.

“Recent advances in surgical options help us achieve our goal of preserving as much function as possible so kids can get back to being kids and doing what they love to do,” says Dr. Amir Misaghi, pediatric orthopaedic oncology surgeon at CHOC. “With advances in growing-type prostheses for limb salvage and restoration, we are able to meet this goal now more than in the past.”

Dr. Amir Misaghi, pediatric orthopaedic oncology surgeon at CHOC

3D printing is also revolutionizing the field of orthopaedic oncology, allowing surgeons to print custom bone models for surgical planning.

“When you do so much preoperative planning, the actual surgical time can be minimized,” says Dr. Misaghi. “We’re also using 3D-printed custom cutting guides to help make the surgery as precise as possible, which helps preserve as much of the patient’s native tissue as possible.”

When it comes to the bone and soft tissue sarcoma program at CHOC, Dr. Rubin and Dr. Misaghi emphasize the robust team and comprehensive capabilities.

“Between oncology, orthopaedic surgery, plastic surgery and radiology, as well as general surgery and pathology, we really have the full package here at CHOC,” Dr. Misaghi says. “We are fully equipped to take care of all benign and malignant bone and soft tissue tumors, and we all focus specifically on pediatrics.”

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.

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MRI-Guided Laser Ablation with Stereotactic Assistance Targets Epilepsy, Tumors

Laser interstitial thermal therapy (LITT), or laser ablation, is among the latest advancements in minimally invasive neurosurgery, allowing surgeons to reach difficult areas of the brain — and offering less risk to patients at the same time.

“Instead of performing a craniotomy, which entails making a large incision and opening up the skull, we place a probe through a small hole in the skull a few millimeters in diameter,” says Dr. Joffre Olaya, pediatric neurosurgeon at CHOC. “Then, under MRI visualization, we deliver heat to the specific area, which destroys the abnormal tissue. Laser ablation is especially useful in patients with small seizure foci or tumors, particularly if they are deep.”

Dr. Joffre Olaya, pediatric neurosurgeon at CHOC

The benefits this minimally invasive approach provides to patients are especially welcoming. “For a craniotomy, patients will be in the hospital for three to five days, in the ICU most likely for a day or two, and they’ll experience discomfort from the skin and muscles on the head,” Dr. Olaya says. “With laser ablation, patients typically go home within a day or two and recover pretty quickly. They also experience less blood loss, pain and side effects overall. Also, laser ablation doesn’t prevent patients from having another procedure. If the tumor is still growing or the seizures are still continuing after ablation, I can go back and perform another laser ablation or a craniotomy.”

To increase surgical precision and accuracy when ablating brain tumors, deep lesions and tissue in the brain where seizures occur, Dr. Olaya employs a ROSA™ (robotic stereotactic assistance) robot.

“We obtain preoperative imaging studies and load those into the ROSA system, which allows us to plan the entry point and trajectory so we can precisely place the laser. This precision helps us to not only locate and effectively ablate our target, but avoid hitting blood vessels or causing unintended damage to surrounding tissues,” Dr. Olaya says. “We were the first pediatric center on the West Coast to have this technology. We use ROSA for multiple conditions, including patients with epilepsy and oncology patients with tumors.”

ROSA’s precision also helps minimize some risks commonly associated with surgery. “ROSA is an amazing tool that yields many benefits for our patients, including less time under anesthesia in the operating room,” Dr. Olaya says. “It also reduces blood loss and risk of infections.”

Although CHOC is at the forefront utilizing the latest technologies to best treat its patients in a minimally invasive manner when possible, Dr. Olaya says CHOC’s team approach to patient care is what sets it apart from other centers in the region.

“I’m really excited that CHOC is investing in this newer technology and it’s available here to provide to our patients, but our team mentality and how well we work together is crucial. Our epileptologists, radiologists, neuropsychologists, all of us really work well together as a team to identify the best candidates for this technology and to provide the best outcomes for our 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 neurology/neurosurgery specialty.

Learn how CHOC’s neuroscience expertise, coordinated care, innovative programs and specialized treatments preserve childhood for children in Orange County, Calif., and beyond.

Multi-Focus Seizures Complicate Surgical Treatment for Pediatric Epilepsy Case

During Celeste’s pregnancy, an ultrasound showed that her baby had heart abnormalities. Once baby Jaylynn was born, further diagnostic evaluation confirmed she had tuberous sclerosis complex (TSC), a disorder that causes growths in multiple organs, including the heart, brain, kidneys and lungs. TSC is a genetic disorder, and patients with this condition are known to have a high seizure burden.

In the days after her birth, the right side of Jaylynn’s body seemed to twitch, and Celeste’s instincts told her Jaylynn was having seizures. Celeste mentioned this to her nurse at the hospital where Jaylynn was born, but her worries were dismissed. After being sent home, Celeste called CHOC Children’s and met with Dr. Lily Tran, a pediatric epileptologist at CHOC’s level 4 pediatric epilepsy center.

Over the next three years, Jaylynn tried several different treatment options, including medications, ketogenic diet and steroid treatment. Most treatments followed the same pattern: the seizures would stop for a few months, but then come back stronger than before. She regressed significantly in terms of development, no longer made eye contact, could not sit up even with support and was lethargic all day due to the high seizure burden. She started losing weight and had to have a G-tube placed for adequate nutrition. Her medication regimen was at high doses to control seizures, which led to side effects, such as vomiting and lethargy, which impacted her quality of life significantly. Her days consisted of seizures, vomiting and sleep. At that point, Celeste said her family was simply trying to survive.

“Jaylynn’s refractory case of epilepsy was quite complex because we couldn’t pinpoint where her seizures were coming from based on Phase I surface EEG monitoring,” says Dr. Tran. “We used several different imaging techniques to locate the focus of her seizures, including a virtual reality simulation program. Through these tests and Phase II invasive EEG monitoring, we found her seizures were coming from the left side of her brain, but on this one side, we then found the seizures were coming from three distinct areas. Her case was discussed extensively at our comprehensive epilepsy surgery conference, but there was no clear-cut answer and consensus on what to do next. Each approach had various pros and cons, and each option had questions and concerns. As a team, we constantly asked ourselves, ‘What’s best for Jaylynn?’ when considering these treatment options. Mom was updated at every step of the way so she could make the most informed decision for her daughter.”

Because the seizure focus came from three different areas in the left hemisphere, it was not reasonable to resect these regions separately without significantly more post-operative side effects. Dr. Tran elected to proceed with a functional hemispherectomy to give Jaylynn the best outcome for seizure control and to turn her quality of life around. The procedure essentially “quieted down” the electrical activity in the left side of her brain.

“For Jaylynn, I used everything I learned in fellowship, consulted with other colleagues and leveraged the tools we have at CHOC — such as our ability to perform invasive surgery and our research capabilities — to determine the best course of treatment for this complex epilepsy case. When you have a multidisciplinary team like ours that includes a dedicated neurosurgeon, neuroradiologists, neuropsychologists, educated nurses, EEG technologists, epilepsy pharmacists, social workers and parent champions who work cohesively together, it helps make the patient’s journey a little bit easier.”

Today, Jaylynn is seizure-free and on fewer medications. She is now laughing and smiling, more interactive, enrolled in school and even got to visit Disney World.

“What makes CHOC different from similar centers, I think, is our focus on the patient journey and how we value the quality of life for each patient,” says Dr. Tran. “We treat every child and their family as a whole unit. When you come to CHOC, you’re not just our patient. You truly become part of our family.”

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 neurology/neurosurgery specialty.

Learn how CHOC’s neuroscience expertise, coordinated care, innovative programs and specialized treatments preserve childhood for children in Orange County, Calif., and beyond.

Silk Biomaterial Research Advances Urologic Treatment Capabilities

The Urology Center at CHOC Children’s is collaborating with Joshua Mauney, PhD, associate professor of urology/biomedical engineering and Jerry D. Choate Presidential Chair in Urology Tissue Engineering in the University of California, Irvine Urology Department, who focuses his research on tissue engineering with the development of silk biomaterials for the repair of visceral hollow organs. Dr. Mauney has a productive basic science laboratory with NIH grant funding and was previously a staff scientist in the Department of Urology at Boston Children’s Hospital and associate professor of surgery at Harvard Medical School.

“The overall goal is the creation of clinically useful scaffold configurations for hollow organ regeneration by engineering materials which fulfill structural and mechanical requirements of native tissues as well as present microenvironmental cues necessary for host tissue integration and defect consolidation,” said Dr. Mauney.

3D matrix designs using silk biomaterials can be used to restore function related to injury or fibrotic disease. Silk scaffolds offer advantages over non-biomaterial implants for human bladder augmentation and can support bladder storage, voiding function and defect correction.

“The addition of Dr. Mauney allows the CHOC team to focus on the reconstruction of bladders and organs using his 3D matrix designs to offer options for children born with missing or abnormal parts of their urinary tract,” said Dr. Antoine “Tony” Khoury, chief of pediatric urology.

Dr. Tony Khoury, chief of pediatric urology at CHOC
Dr. Tony Khoury, chief of pediatric urology at CHOC

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.

US News and World Report, Urology

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