Impatient for Change
When Dr. Daniel Pollyea, Director of Leukemia Services at University of Colorado Hospital, reflects on his experience treating patients with acute myeloid leukemia (AML), he alternates between optimism and frustration.
“We have an incredible opportunity to develop better treatment options – and even cures – for people with AML,” he says. “Still, right now every aspect of this disease represents an unmet need.”
During his residency, Dr. Pollyea was quickly drawn to a focus on AML, a disease caused by abnormalities in an early stage of myeloid cells in the bone marrow. It’s often known as the pervasive aggressor among other types of leukemia, as treating it (with therapies including chemotherapy, radiation and bone marrow transplant) is incredibly difficult in the group of people it most often strikes: adults older than 60.
When it comes to treating this older population, Dr. Pollyea and his colleagues face a number of limitations: “The disease biology is actually worse in older populations and, on top of that, it is more difficult for them to tolerate the standard of care therapies,” he explains.
What is it that makes a disease like AML so much more challenging if you are a senior? Here, we take a further look at the odds facing older people with AML:
When Age Is More Than a Number
The median age at AML diagnosis is 67 years. At this age, the curability rate is between 5-15 percent, much lower than it is for younger adults or children, but the reason why is less clear.
“We know that older patients are less likely to respond to conventional treatments and less likely to achieve remission,” Pollyea explains. “And they are much less likely to have a favorable risk profile that’s associated with good long-term outcomes and cures. The reason why is largely unknown, but it’s clear that this disease is biologically different in older populations than a younger population. It’s just a different disease.”
Looking at Genetic Mutations
But what makes AML look different as you age? The answer may lie in each person’s genes. Throughout our lives, our DNA changes and mutates, resulting in a uniquely characteristic pattern called a genetic signature.
When it comes to AML, researchers from the University of Toronto have narrowed the signatures down to a group of specific genes that are most critical for predicting outcomes. But for those who are older, this deeper understanding of our genetic profiles has led to another hurdle: scientists have learned that people over age 60 are more prone to have one of the genetic signatures that leads to less favorable outcomes.
Why Medical History Makes a Difference
A huge concern for those who have been treated for cancer once is that it may one day come back, or that they may get a “second cancer.” And, as the pervasive aggressor, AML can often appear as that second cancer; those with a history of certain blood disorders are more likely to develop AML later on.
Dr. Pollyea explains why: “Exposure to chemotherapy or radiation for another cancer in some patients can cause leukemia to develop later in life. Oncologists are getting better and better at treating or curing other malignancies, and so as these patients live longer, we are seeing some developing 'treatment related AML' later in life, due to genetic mutations that arise out of previous therapies.”
This risk peaks about eight years after chemotherapy – one more thing stacked against those who are older, and already survivors of cancer.
The Search for New Therapies
Though we know more today about the biology and genetics of AML than we did just a decade ago, one thing still remains very limited – the availability of treatment options.
“When I have a younger patient, we admit them right away for a month long stay in the hospital to receive induction chemotherapy. This is an intensive process that we hope will get a patient into remission,” Dr. Pollyea says. “But most older patients are not candidates for that intense of an approach, and they could even die from the treatment.”
So, when Dr. Pollyea sees a patient who is not a candidate for the standard of care treatment – intensive chemotherapy with or without a bone marrow transplant – instead he considers a gentler form of chemotherapy with fewer side effects.
Dr. Pollyea struggles with the limitations of this approach, noting, “A minority of patients respond and even then they do not respond for long. I think providers know this and that is the reason why many older patients are not even treated and sent right to hospice at the time of diagnosis.”
Looking to the Future
Dr. Pollyea faces this challenge head on every day, giving as many people more time and quality of life as possible. And he’s hopeful about a future with more targeted treatment options.
“If we could zero in on specific mutations and target them, even the toughest patients to treat may have a chance,” he says.
With our growing knowledge of the biology of AML and its many influences, there may one day be more potential to treat individuals based on genetic differences.