Dr. Todd Cooper
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Dr. Todd Cooper has spent his career focused on refining the way pediatric leukemias are treated, especially for patients with a high-risk diagnosis. Now leading the COG’s Acute Myeloid Leukemia Committee, Dr. Cooper shares how the committee is making monumental progress toward improving survival rates for AML patients and what’s on the horizon for their strategic priorities.
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Pediatric oncologist, Todd Cooper, DO, has turned his disappointment in the lack of effective treatments for children with cancer into unwavering motivation. This eventually led him to direct Seattle Children’s Leukemia and Lymphoma Program and to design a High-Risk Leukemia Program that’s one of only a few in the country specializing in treating children with relapsed and refractory leukemias and acute myeloid leukemia (AML).
Dr. Cooper also co-leads the Leukemia & Lymphoma Society’s Pediatric Acute Leukemia (PedAL) Initiative and serves as the chair of the Children’s Oncology Group’s (COG) Acute Myeloid Leukemia Committee.
We connected with him to learn more about how COG’s AML committee is working to identify the root cause and unique types of AML, while also pursuing innovative treatments.
Dr. Cooper also co-leads the Leukemia & Lymphoma Society’s Pediatric Acute Leukemia (PedAL) Initiative and serves as the chair of the Children’s Oncology Group’s (COG) Acute Myeloid Leukemia Committee.
We connected with him to learn more about how COG’s AML committee is working to identify the root cause and unique types of AML, while also pursuing innovative treatments.
Q: What’s unique about acute myeloid leukemia (AML)?
AML happens when myeloid cells – cells that turn into white or red blood cells or platelets – don’t mature properly. There are many biological reasons for this to happen, including mutations or fusions, and sometimes both, that can change the normal programming of a cell.
About 500 patients are diagnosed with AML each year. And about 10% of those patients carry germline mutations – meaning there is something in the patient’s DNA, passed down from one or both parents that triggers the AML. The fact that the disease has many root causes makes treating it even more complicated because each can respond to treatments differently.
Q: What’s challenging about treating AML?
AML can be difficult to treat because this type of cancer is really good at resisting chemotherapies and it advances quickly. Therefore, current treatment protocols for AML require highly toxic chemotherapies.
Powerful chemotherapies are often our best defense against a disease that has a lower survival rate than other childhood leukemias. But these therapies are extremely hard on a child’s organs. If a child needs a bone marrow transplant, we have the added challenge of quickly identifying a match and keeping them healthy enough to handle the transplant procedure.
We’ve identified mutations and fusions for about 55% of patients, so for this group, we have a more clear roadmap for treatment. For the other 45% of patients, we use standard medications that have been in use for decades. As we identify more unique subsets of AML and their characteristics, we’ll study them and work on more advanced treatment plans.
Q: Can you share a couple of the committee’s recent successes?
Overall, the myeloid disease committee has been successful in developing protocols for children and young adults who have a diagnosis that lives within the family of myeloid neoplasm diseases, like AML, Acute Promyelocytic Leukemia (APL), Chronic myeloid leukemia (CML) and myeloid leukemia of Down Syndrome (ML-DS).
Because of COG’s global reach and outstanding infrastructure, we have been able to recruit patients with these rare diseases to several clinical trials, helping us learn about the uniqueness of each type of cancer.
Among our successes are two studies of therapies for subsets of patients with myeloid malignancies (diseases that have spread to more than one place in the body).
One of those studies was a trial led by Matthew, Kutny, M.D. at the Children’s Hospital of Alabama. His phase 3 trial (AAML1331) showed one of the intense chemotherapies newly diagnosed APL patients receive could be replaced with two therapeutic agents, which work together to help newly developed cells mature into normal cells, instead of leukemia. Incredibly, Dr. Kutny’s study demonstrated an overall survival rate of 99% for these patients.
The other trial was made possible by the approval of gemtuzumab ozogamicin for pediatric AML patients. This therapy targets the CD33 antigen that lives on the surface of AML cells. At Children’s Mercy, Alan Gamis, M.D. (AAML0531) is leading the efforts to define how best to utilize this therapy which has reduced relapse rates for all AML patients especially those with the FLT3-ITD and KMT2a mutations.
Together, these studies represent our greatest hope for the future – treatments that greatly improve survival rates and are less toxic to patients’ bodies.
Another big win for us are positive results from a phase 3 trial led by Richard Aplenc, M.D., Ph.D. with the Children’s Hospital of Philadelphia and Jessica Pollard, M.D. at Boston Children’s. Their study of an inhibitor therapy targeting the FLT3-ITD mutation has improved survival rates for this subset of patients.
We’re also looking at improving short and long-term survivorship care for AML patients. Dr. Aplenc and Kelly Getz, Ph.D., at Children’s Hospital of Philadelphia, have published findings and continue to study (dexrozoxane) a cardio-protective agent that can minimize heart damage often caused by AML treatments.
We’re thrilled with these outcomes that show that developing less toxic regimens and improving survival rates is possible.
AML happens when myeloid cells – cells that turn into white or red blood cells or platelets – don’t mature properly. There are many biological reasons for this to happen, including mutations or fusions, and sometimes both, that can change the normal programming of a cell.
About 500 patients are diagnosed with AML each year. And about 10% of those patients carry germline mutations – meaning there is something in the patient’s DNA, passed down from one or both parents that triggers the AML. The fact that the disease has many root causes makes treating it even more complicated because each can respond to treatments differently.
Q: What’s challenging about treating AML?
AML can be difficult to treat because this type of cancer is really good at resisting chemotherapies and it advances quickly. Therefore, current treatment protocols for AML require highly toxic chemotherapies.
Powerful chemotherapies are often our best defense against a disease that has a lower survival rate than other childhood leukemias. But these therapies are extremely hard on a child’s organs. If a child needs a bone marrow transplant, we have the added challenge of quickly identifying a match and keeping them healthy enough to handle the transplant procedure.
We’ve identified mutations and fusions for about 55% of patients, so for this group, we have a more clear roadmap for treatment. For the other 45% of patients, we use standard medications that have been in use for decades. As we identify more unique subsets of AML and their characteristics, we’ll study them and work on more advanced treatment plans.
Q: Can you share a couple of the committee’s recent successes?
Overall, the myeloid disease committee has been successful in developing protocols for children and young adults who have a diagnosis that lives within the family of myeloid neoplasm diseases, like AML, Acute Promyelocytic Leukemia (APL), Chronic myeloid leukemia (CML) and myeloid leukemia of Down Syndrome (ML-DS).
Because of COG’s global reach and outstanding infrastructure, we have been able to recruit patients with these rare diseases to several clinical trials, helping us learn about the uniqueness of each type of cancer.
Among our successes are two studies of therapies for subsets of patients with myeloid malignancies (diseases that have spread to more than one place in the body).
One of those studies was a trial led by Matthew, Kutny, M.D. at the Children’s Hospital of Alabama. His phase 3 trial (AAML1331) showed one of the intense chemotherapies newly diagnosed APL patients receive could be replaced with two therapeutic agents, which work together to help newly developed cells mature into normal cells, instead of leukemia. Incredibly, Dr. Kutny’s study demonstrated an overall survival rate of 99% for these patients.
The other trial was made possible by the approval of gemtuzumab ozogamicin for pediatric AML patients. This therapy targets the CD33 antigen that lives on the surface of AML cells. At Children’s Mercy, Alan Gamis, M.D. (AAML0531) is leading the efforts to define how best to utilize this therapy which has reduced relapse rates for all AML patients especially those with the FLT3-ITD and KMT2a mutations.
Together, these studies represent our greatest hope for the future – treatments that greatly improve survival rates and are less toxic to patients’ bodies.
Another big win for us are positive results from a phase 3 trial led by Richard Aplenc, M.D., Ph.D. with the Children’s Hospital of Philadelphia and Jessica Pollard, M.D. at Boston Children’s. Their study of an inhibitor therapy targeting the FLT3-ITD mutation has improved survival rates for this subset of patients.
We’re also looking at improving short and long-term survivorship care for AML patients. Dr. Aplenc and Kelly Getz, Ph.D., at Children’s Hospital of Philadelphia, have published findings and continue to study (dexrozoxane) a cardio-protective agent that can minimize heart damage often caused by AML treatments.
We’re thrilled with these outcomes that show that developing less toxic regimens and improving survival rates is possible.
Q: How is the committee working to improve outcomes for kids who relapse?
About 30-40% of AML patients either don’t achieve remission with initial therapy or subsequently relapse. Putting those kids through another series of treatments is one of the most difficult parts of our job. We carefully examine their treatment plans to be sure we’re doing everything we can to give them the best possible outcome.
Making discoveries that will improve outcomes and launching trials for these patients is essential. One of COG’s biggest partners is the Leukemia & Lymphoma Society, which helped our COG committee develop the Pediatric Acute Leukemia (PedAL) Initiative, which is part of their Dare to Dream Project. The purpose of PedAL is to provide unique genetic information about a child’s AML at relapse, to screen for the presence of targets for relapse therapies, and to provide eligibility information for promising clinical trials.
About 30-40% of AML patients either don’t achieve remission with initial therapy or subsequently relapse. Putting those kids through another series of treatments is one of the most difficult parts of our job. We carefully examine their treatment plans to be sure we’re doing everything we can to give them the best possible outcome.
Making discoveries that will improve outcomes and launching trials for these patients is essential. One of COG’s biggest partners is the Leukemia & Lymphoma Society, which helped our COG committee develop the Pediatric Acute Leukemia (PedAL) Initiative, which is part of their Dare to Dream Project. The purpose of PedAL is to provide unique genetic information about a child’s AML at relapse, to screen for the presence of targets for relapse therapies, and to provide eligibility information for promising clinical trials.
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In just two and a half years, the relapse study has already enrolled 315 children. That’s remarkable because it exceeds the total number of children enrolled in AML relapse studies in the previous 15 years.
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Can you explain a bit more about the role of biologists on the AML committee?
Our subcommittee of biologists is amazing and we couldn’t do anything without them. Katherine Tarlock, M.D., who works with me at Seattle Children’s, leads the biology efforts on the AML committee, and this group has identified several new genetic mutations in the last few years, allowing us to classify new subsets of AML. She works closely with Soheil Meshinchi, M.D., Ph.D., at the Fred Hutchison Cancer Center who served as the previous AML biology chair and is a leading international expert in AML research.
Identifying the cause of a child’s cancer is key to developing the most effective treatments. Sometimes, when we’re lucky, a drug already exists for other cancers that targets a mutation or gene that is also present in AML. The biology team helps us make those matches. So, in many ways, they are leading our path to discoveries.
Our subcommittee of biologists is amazing and we couldn’t do anything without them. Katherine Tarlock, M.D., who works with me at Seattle Children’s, leads the biology efforts on the AML committee, and this group has identified several new genetic mutations in the last few years, allowing us to classify new subsets of AML. She works closely with Soheil Meshinchi, M.D., Ph.D., at the Fred Hutchison Cancer Center who served as the previous AML biology chair and is a leading international expert in AML research.
Identifying the cause of a child’s cancer is key to developing the most effective treatments. Sometimes, when we’re lucky, a drug already exists for other cancers that targets a mutation or gene that is also present in AML. The biology team helps us make those matches. So, in many ways, they are leading our path to discoveries.
Q: What are the AML committee’s top priorities for the next 3-5 years?
Right now, we’re focused on developing even more clinical trials that offer the most promising therapies for newly diagnosed patients. While it is important to have new drugs available for children who relapse, it is also critically important to find ways to use therapies early to prevent AML recurrence and hopefully, spare children from even more toxic therapies if their leukemia comes back.
Like the FLT3-ITD inhibitor, we’re excited about an inhibitor targeting the interaction between KMT2a (formerly referred to as the mixed lineage leukemia gene) and menin protein. When these two proteins are allowed to interact, it changes the normal maturation process of myeloid cells and leads to AML. Menin inhibitors prevent menin-KMT2a interaction, allowing the cells to mature normally and eventually stop the production of leukemia cells. The COG myeloid committee, in collaboration with the PedAL initiative, are developing clinical trials for children with mutations that may be responsive to menin inhibition.
Another big priority for us is identifying new therapeutic targets and pinpointing cancer-causing mutations and fusions for those who don’t have therapies that match up with their biology. When we have a clear understanding of a cancer’s root cause, we have more opportunities to treat it.
Our committee is also working to recruit the next generation of leaders at every level to study rare cancers. We need more biologists and statisticians, and we need clinicians, pathologists and people who can design trials. By developing these future leaders, we can be more hopeful that we will cure more children with myeloid malignancies and see them lead long, fruitful lives.
Q: How can families and the greater community support AML research?
For a long time, clinicians and scientists could only move at the pace of what government funding allotted us. That has changed significantly in the last couple of decades. Philanthropy has played a part in every one of our discoveries. Families who have experienced the worst of what pediatric cancer involves are extremely motivated, and their communities support them.
Family-led and community-based fundraising events don’t just raise money, they raise awareness about why research focused on treating cancers with minimal harm is so important. These voices are an extension of COG’s mission and of our hospital teams and labs – and they’re louder than we could ever be. I’m extremely grateful for our supporters because I know that, for a majority of them, their gift represents a child they are connected to.
Q: What makes you hopeful about the future of AML research?
The capacity for us to do biological and genetic testing on cancer cells is opening doors quickly. Building the PedAL Initiative is a huge step for us who focus on leukemias. In the last couple of years, COG also launched the Molecular Characterization Initiative, an intensive testing of patients' DNA and RNA as well as their tumors’ biological characteristics.
What we’ve learned about the DNA and RNA for central nervous system tumors and soft tissue sarcomas makes me hopeful that genetic testing for high-risk leukemias will give us crucial information about myeloid leukemias.
This is another place where donors can be the driver we need to move forward. Biological and genetic testing is rarely covered by insurance. Funding projects that offer every patient genetic testing trigger a hugely positive cascading effect on a patient’s treatment. The point is to save as many lives as possible and get kids back home.
Q: What’s the best part about your job?
The reason I went into pediatric cancer is still the reason why I do it: My interactions with patients and their families.
When I was a teenager in North Georgia, I worked at a summer camp in the Appalachian Mountains. For one week, the camp was reserved for children with cancer. Those campers had a deep curiosity, enthusiasm and love for life. Being a positive part of their life and healing was inspiring and rewarding. It led me down the path to becoming a pediatric oncologist.
Today, knowing our patients and their families, and uniting around them with our nursing team, is a powerful motivator to do the other part of my job – in research. Being on the cutting edge of new treatments and discoveries keeps the work interesting. Collaborating with all the like-minded people across a variety of disciplines across COG who are so dedicated to improving survival rates completes the circle.
Right now, we’re focused on developing even more clinical trials that offer the most promising therapies for newly diagnosed patients. While it is important to have new drugs available for children who relapse, it is also critically important to find ways to use therapies early to prevent AML recurrence and hopefully, spare children from even more toxic therapies if their leukemia comes back.
Like the FLT3-ITD inhibitor, we’re excited about an inhibitor targeting the interaction between KMT2a (formerly referred to as the mixed lineage leukemia gene) and menin protein. When these two proteins are allowed to interact, it changes the normal maturation process of myeloid cells and leads to AML. Menin inhibitors prevent menin-KMT2a interaction, allowing the cells to mature normally and eventually stop the production of leukemia cells. The COG myeloid committee, in collaboration with the PedAL initiative, are developing clinical trials for children with mutations that may be responsive to menin inhibition.
Another big priority for us is identifying new therapeutic targets and pinpointing cancer-causing mutations and fusions for those who don’t have therapies that match up with their biology. When we have a clear understanding of a cancer’s root cause, we have more opportunities to treat it.
Our committee is also working to recruit the next generation of leaders at every level to study rare cancers. We need more biologists and statisticians, and we need clinicians, pathologists and people who can design trials. By developing these future leaders, we can be more hopeful that we will cure more children with myeloid malignancies and see them lead long, fruitful lives.
Q: How can families and the greater community support AML research?
For a long time, clinicians and scientists could only move at the pace of what government funding allotted us. That has changed significantly in the last couple of decades. Philanthropy has played a part in every one of our discoveries. Families who have experienced the worst of what pediatric cancer involves are extremely motivated, and their communities support them.
Family-led and community-based fundraising events don’t just raise money, they raise awareness about why research focused on treating cancers with minimal harm is so important. These voices are an extension of COG’s mission and of our hospital teams and labs – and they’re louder than we could ever be. I’m extremely grateful for our supporters because I know that, for a majority of them, their gift represents a child they are connected to.
Q: What makes you hopeful about the future of AML research?
The capacity for us to do biological and genetic testing on cancer cells is opening doors quickly. Building the PedAL Initiative is a huge step for us who focus on leukemias. In the last couple of years, COG also launched the Molecular Characterization Initiative, an intensive testing of patients' DNA and RNA as well as their tumors’ biological characteristics.
What we’ve learned about the DNA and RNA for central nervous system tumors and soft tissue sarcomas makes me hopeful that genetic testing for high-risk leukemias will give us crucial information about myeloid leukemias.
This is another place where donors can be the driver we need to move forward. Biological and genetic testing is rarely covered by insurance. Funding projects that offer every patient genetic testing trigger a hugely positive cascading effect on a patient’s treatment. The point is to save as many lives as possible and get kids back home.
Q: What’s the best part about your job?
The reason I went into pediatric cancer is still the reason why I do it: My interactions with patients and their families.
When I was a teenager in North Georgia, I worked at a summer camp in the Appalachian Mountains. For one week, the camp was reserved for children with cancer. Those campers had a deep curiosity, enthusiasm and love for life. Being a positive part of their life and healing was inspiring and rewarding. It led me down the path to becoming a pediatric oncologist.
Today, knowing our patients and their families, and uniting around them with our nursing team, is a powerful motivator to do the other part of my job – in research. Being on the cutting edge of new treatments and discoveries keeps the work interesting. Collaborating with all the like-minded people across a variety of disciplines across COG who are so dedicated to improving survival rates completes the circle.