Advances in Treating Pediatric High-Risk Leukemia: A Q&A With Dr. Todd Cooper
September 7, 2022
Dr. Todd Cooper is Section Chief of Oncology, Director of the Pediatric Leukemia/Lymphoma Program and Co-Director of the High-Risk Leukemia Program at Seattle Children’s. The High-Risk Leukemia Program at Seattle Children’s started in 2018 under the leadership of Dr. Cooper and Dr. Marie Bleakley, Director of Cellular Therapy and Transplantation for Pediatric Leukemia at Fred Hutchinson Cancer Center.
Q: Can you give us a quick reminder of what high-risk leukemia (HRL) is?
By high-risk, we mean leukemia that is likely to come back after treating it with standard therapy. This also includes leukemia that doesn’t go into remission quickly after treatment or has come back. Our program takes care of patients in whom hematopoietic stem cell transplantation is likely to be needed or if the disease has biologic markers that predict it’s more likely to return after treatment.
Q: What can you tell us about the pace and prospects of HRL research and treatment today?
The pace of research on hard-to-treat pediatric leukemia has accelerated exponentially over the last decade. One major reason has been advances in our understanding of the biology surrounding acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). Understanding the disease biology better is helping us develop better, targeted treatments. These include novel drugs that attack newly discovered targets and therapies that harness the immune system to attack leukemia in the body.
Q: How have recent research advances translated to better patient care?
Kids here have access to some of the best care in the world. We can now provide next-generation sequencing to every newly diagnosed leukemia patient and high-risk leukemia patient who comes through our doors. This can lead to quicker diagnoses of complex diseases. In some patients, it yields important biologic information we use to customize a superior treatment. Seattle Children’s also has its own CAR-T cell immunotherapy program dedicated exclusively to kids, meaning we can bring new treatments to kids more quickly. This sets us apart from almost all other institutions.
The Pediatric Blood and Marrow Transplant Program, part of Seattle Children’s Cancer and Blood Disorders Center and the Fred Hutchinson Cancer Center (Fred Hutch), is one of the most established and largest programs in the world. It has a strong history of cutting-edge clinical trials in pediatric blood and marrow transplantation (BMT). For example, we have new BMT strategies developed in Seattle that have been so successful in local trials that they are now being evaluated in national trials conducted by the Pediatric Transplantation and Cell Therapy Consortium and National Marrow Donor Program.
Q: What’s next on the horizon for high-risk leukemia research?
Researchers around the world have embarked on a global initiative to identify biologic targets for all kids with acute leukemia, the LLS Pediatric Acute Leukemia (PedAL) Initiative. We hope the work will lead to targeted therapies for leukemia, meaning either targeted chemotherapies or targeted immune-based therapies.
Q: How much is our region a part of these research advances?
There is a large group of doctors at Seattle Children’s and Fred Hutch who are deeply involved in leading research on HRL. Our colleague Dr. Soheil Meshinchi at Fred Hutch is the national and international leader in genomics and targets for the treatment of AML. He leads the biologic discovery efforts associated with PedAL.
From the Seattle Children’s side, I’m the clinical trial chair of PedAL and head of the current phase 3 trial for newly diagnosed AML, and chair of the Children’s Oncology Group (COG) committees on New Agents for AML and Relapsed AML. Dr. Marie Bleakley leads the BMT program for hematologic malignancies and leads national clinical trials for novel BMT strategies and immune-based therapies. Dr. Katherine Tarlock and Dr. Adam Lamble are leading 2 of the national PedAL trials for relapsed AML. Immunotherapy scientists Drs. Michael Jensen and Rebecca Gardner lead Seattle Children’s immunotherapy program, dedicated to immune-based therapies specifically for children and young adults with cancer.
Q: What are the biggest challenges in providing HRL treatment and research today?
One of the biggest challenges is access to new agents. Our hope is that this is being addressed through PedAL. In the current state, drug development is geared towards adults. Typically drug development and approval of novel therapies for kids happens very slowly and only after drugs are through most of the approval process in adults. This can take many years and can be frustrating in that access to new therapies for children can be very limited.
PedAL is addressing this barrier to access of new therapies to children by helping to engage our industry partners and the regulatory agents that mediate drug approval. This is an amazing development and we are so appreciative. It is the most promising development in access to new therapies for children in my career.
Q: You started the HRL Program at Seattle Children’s in 2018. Is there a particular accomplishment you’re most proud of?
I’m so proud that we have been able to change the paradigm for caring for our highest-need leukemia patients at Seattle Children’s. We’ve developed a new model of care where we bring a multi-disciplinary team together to meet directly with the patient and family to come up with the best individual treatment plan for the child and family. With the opening of our new clinic in the new Forest B building, we will be able to make this happen in an outpatient room designed just for them, instead of asking them to move from office to office around the building visiting different doctors. We hope that it will make their visits more efficient, more comfortable, and more productive. It helps our care teams too by keeping them in close proximity to the patients and each other; they have shared workspaces near their patients which helps them communicate and collaborate more seamlessly and in real-time.
We were the first to formalize this sort of model of care in our HRL Program and it’s now being emulated at other leading institutions. It’s part of the reason that we now have a national reputation for specializing in difficult-to-treat leukemia cases. We are routinely approached for second opinions by parents and providers from around the country and the world. We’re proud of that.
Q: HRL patients sometimes need a hematopoietic stem cell transplantation (BMT). Are there new advancements coming in this area?
There are new approaches to BMT that are improving the outcomes of HRL that require this type of therapy. One new strategy called “naïve T cell depletion” involves removing a type of white blood cell from the cell product that is given to patients at the time of BMT in order to reduce a complication called “graft-versus-host disease.” We also have a leading pediatric cord blood transplantation program that has several active trials.
This isn’t a research development per se, but it’s important: Our Pediatric Blood and Marrow Transplant Program is relocating this fall to the hospital’s new wing (Forest B) which means we will have all of our region’s pediatric BMT services under one roof for the first time. Outpatient transplant services that were previously only available at Fred Hutch will be at Seattle Children’s.
Q: How does the HRL program include referring providers in their patient’s care?
We ask referring providers to join an initial discussion with the patient and family, which is virtual and includes an oncologist, transplant physician, nurse practitioner and nurse coordinator. We then have an in-person multi-disciplinary visit and communicate closely with the referring provider, when applicable.
Q: Finally, what else do you want other providers to know about high-risk leukemia?
With leukemia that is difficult to treat, multi-disciplinary care (oncologists, transplanters, sub-specialists) is essential. Also critical is the timing of these tailored therapies and BMT. Our program has an integrated approach to diagnosis and therapy that is critical for optimal outcomes. I would encourage oncology providers to contact us in the event a patient isn’t responding well to therapy, has leukemia that has relapsed, needs alternative therapies and/or will need a BMT.