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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Multidisciplinary Approach to Pediatric Cancer Treatment Benefits an Underserved Young Adult Population

As one of the most robust adolescent and young adult (AYA) pediatric cancer programs in the nation, CHOC’s AYA program offers more than comprehensive oncology care to an underserved teen and young adult population — it’s a model for other AYA programs in the country to build upon.

“In the last 15 years or so, we’ve realized there is a huge survival gap in the AYA population, everyone from the age of 15 to 39 years old, whereas over the past 30 to 40 years, we’ve seen significant survival gains in pediatric patients and older adults,” says Dr. Jamie Frediani, pediatric oncologist at the Hyundai Cancer Institute at CHOC. “The AYA population has had very few survival gains, and we believe this is because of a multitude of reasons. They are much less likely to enroll in clinical trials or have access to clinical trials, they do not have the same access to novel new experimental treatments that can improve their survival, their tumor biology is likely different and then there’s a whole host of psychosocial reasons. AYA patients really are their own unique population, and the AYA program at CHOC aims to address that survival gap and to address it from a multipronged approach.”

The multipronged CHOC AYA program focuses on education, research and psychosocial support to increase survivorship within the AYA population.

“Our patients really want to know more about their disease,” Dr. Frediani says. “They want to know more about how their condition impacts their lives whether they’re in treatment or survivorship, such as fertility and sexual education, for example. Our team of experts have education nights with patients to talk about any topics they want to discuss. We have peer mentorship so patients can talk through the highs and lows they experience with someone who’d been through the same thing they’re going through.”

From a research standpoint, Dr. Frediani says the goals of the program are getting more of the AYA patients into clinical trials, knowing where the clinical trial enrollment gap exists and building relationships with adult counterparts to find the best hospitals where AYA patients can be treated.

“We know pediatric diseases do better if a patient is treated at a pediatric hospital. Finding where these patients will do best and forming those relationships to get the most appropriate care is critical. It’s also about finding everything else they need — the supportive medicine, other drugs and different dosing, clinical trials and research projects.”

Addressing AYA patients’ psychosocial needs is the third prong of CHOC’s AYA program.

“I’m a firm believer that multidisciplinary psychosocial supports plays a huge role,” Dr. Frediani says. “Mental health plays a significant role in the treatment of our AYA patients, and I have to believe that affects their outcomes. AYA patients are at a critical juncture in their lives where they’re trying to seek independence. A lot of them are having kids, getting married, starting new jobs, going to college — all these critical life transitions are happening. When you put cancer on top of that, the natural order of this time in their lives is completely disrupted. Social workers, child life specialists, psychologists, case managers, music therapists — all of our resources help our patients know we truly understand their feelings and needs and are here to help them in every way we can.”

CHOC’s AYA program was developed around 2014 and was one of the only AYA programs in the nation to offer such a comprehensive range of services. Dr. Frediani notes that while some AYA programs in the United States today have a heavier focus on treatment, nurse navigation and clinical trials, others are more support-group focused. CHOC is unique because its program is a hybrid of both.

“Our AYA program has a depth that most programs do not. We have this very robust psychosocial support and clinical trial programming around ours. I think we are unique in the amount of resources we provide for our AYA patients. Addressing cancer from our multipronged approach with a multidisciplinary team ends up being so important.”

The strength of CHOC’s AYA program is rooted in the institution’s values and commitment to providing comprehensive cancer care.

“CHOC comes from a community-based model of medicine,” Dr. Frediani says. “We value the bedside relationships with patients, spending time with them and taking care of not just their medical disease, but everything else around it. I see that across our team, from our nurses to our physicians to our social workers to our child life specialists. Everyone is here to stand with our AYA patients and to help them live whatever life they want to live, in whatever way that means. Other physicians should know CHOC wants to help their AYA patients in any way we can, from offering second opinions to helping with fertility preservation to checking on the availability of a clinical trial. I want to make sure there’s not a person in this age range who goes without these critical resources, without knowing this program is here for them.”

Our Care and Commitment to Children Has Been Recognized

CHOC 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.

Clinical Trials Continue the Advancement of Pediatric Oncology Treatment

Children, adolescents and young adults with cancers that do not respond to traditional treatments continue to find new treatment options because of CHOC’s extensive efforts and active engagement in clinical trial research.

The Hyundai Cancer Institute at CHOC Children’s is a member of the Children’s Oncology Group (COG) and one of only 21 elite facilities in North America and three in California that has received a prestigious Phase 1 clinical trial designation to offer COG’s investigational, potentially promising and innovative clinical trials. COG is the most experienced organization in the world when it comes to the research and development of new therapeutics for children and adolescents with cancer.

“I’ve witnessed the dramatic progress made in the survival of our pediatric patients because of clinical trials,” says Dr. Ivan Kirov, medical director of oncology and the Hyundai Cancer Institute at CHOC Children’s. “Clinical trials are the mortar behind our successes here at CHOC.”

Dr. Ivan Kirov, medical director of oncology and the Hyundai Cancer Institute at CHOC Children’s
Dr. Ivan Kirov, medical director of oncology and the Hyundai Cancer Institute at CHOC Children’s

CHOC currently offers more than 140 clinical trials in varying phases, including multiple pharmaceutical industry-sponsored clinical trials. Besides membership in COG, CHOC is also a member of the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium (TACL), which offers novel treatments in Phase 1 studies for childhood leukemia and lymphoma; the Lymphoma consortium; and the UC Children, Adolescent and Young Adults Cancer Consortium, which includes all of the University of California pediatric oncology programs.

Among the research at CHOC is an upcoming clinical trial for the treatment of diffuse intrinsic pontine glioma (DIPG), a highly aggressive and one of the most difficult-to-treat childhood tumors.

“We are in the process of opening and initiating this clinical trial which, in my opinion, will be extremely important for patients in the future,” Dr. Kirov says. “DIPG is a brainstem tumor which is universally deadly, and very few patients survive more than a year, or even six months. CHOC, the Dana-Farber Cancer Institute in Boston and Lurie Children’s Hospital in Chicago are the only three sites where this new study will be offered. This study will explore a new vaccine for the treatment of DIPG in combination with checkpoint inhibitors. We’re hoping this study will be open in the next several months to offer hope to patients with this disease.”

While clinical research is fundamental to advancing pediatric oncology treatments, Dr. Kirov said the trials themselves are only part of CHOC’s comprehensive approach to helping children and young adults survive cancer.

“These cutting-edge medications and products we are testing, including new targeting agents, monoclonal antibodies and various types of small molecules and vaccines, for example, require an extremely strong supportive and clinical research infrastructure, which CHOC can offer,” says Dr. Kirov. “Our highly educated clinical research coordinators, physicians-scientists, nurses, educators, pharmacists, and other professionals, along with our unparalleled supportive services for both patients and their families, such as social workers, psychologists, child life specialists, palliative care experts and spiritual services, make our patients’ experiences at CHOC unique, and I think this is why CHOC truly stands out. In fact, many patients who come to CHOC for Phase 1 studies express their desire to stay here even after the study is completed, which really speaks very highly of CHOC and the continuum of care and support we provide to young patients and their families.”

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.

The forefront of CAR T-Cell immunotherapy research for high-risk pediatric leukemia patients

Innovative research conducted at the Hyundai Cancer Institute at CHOC Children’s includes investigations into immunotherapy, which has emerged as an effective therapeutic modality for patients with hematologic malignancies. Chimeric Antigen Receptor (CAR) T-cell therapy is capturing the attention of the medical community as a prominent example of cellular immunotherapy and is often referred to as a “living drug.”

“CAR T-cell therapy has revolutionized the treatment landscape of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) — a disease that was historically considered to have a very poor prognosis,” says pediatric oncologist Dr. Van Huynh, who leads the CAR T-cell program at CHOC “With this remarkable approach, we are able to harness the patient’s own immune system to potentially cure their leukemia.”

Dr. Van Huynh, pediatric oncologist at the Hyundai Cancer Institute at CHOC Children’s

CHOC was one of the first pediatric sites for CAR T-cell therapy clinical trials in 2015. Along with providing access to innovative clinical trials for CAR T-cell therapy and other immunotherapy, CHOC is now a certified treatment center for providing the recent U.S. Food and Drug Administration-approved CAR T-cell therapy called KYMRIAH. It is available to pediatric and adolescent/young adult (AYA) patients who are up to 25 years of age with second or later relapse or refractory (R/R) B-cell ALL or patients with R/R large B-cell lymphoma.

CAR T-cell therapy involves the collection of a patient’s own T-cells and genetic modification of these cells to express a CAR that can recognize a tumor antigen such as CD19 on leukemia cells. The CAR T-cells are then expanded in the lab and later re-infused back into the patient, where they continue to expand and seek out the target antigens to eradicate the leukemia.

CAR T-cell therapy has given hope to many patients who otherwise had no other treatment options. Furthermore, dramatic initial clinical responses and high rates of complete remission have been observed. Relapses can occur due to antigen loss (leukemia cells no longer express the target antigen) or CAR T-cell exhaustion (the CAR T-cells no longer provide protection).

“Currently, researchers are looking into ways to overcome these two barriers to make this therapy even more effective,” Dr. Huynh says. “I’m also excited for the potential of CAR-Ts to target other antigens besides CD19 and the possibility that it may be able to treat other types of cancer.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-2021 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.