Decoding Evolving Drivers and Risk Stratification of Acute Leukemias: Tina Bhatnagar, DO

With extensive expertise in treating blood cancers, Bhavana (Tina) Bhatnagar, DO, provides critical insights into the complex drivers behind acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). An associate professor of medicine at West Virginia University Cancer Institute at Wheeling Hospital, she explains that although many factors—including chemical exposures, genetics, and prior cancer treatments—can damage DNA, aging remains a fundamental element in disease development.

“The most common risk factor, which is similar for other cancers, too, is just increasing age,” she says.

Beyond identifying triggers, her work emphasizes the importance of risk stratification by evaluating both patient-related and disease-related factors. By examining the genetic underpinnings and molecular abnormalities of leukemic cells, she helps categorize patients into specific risk groups to better predict outcomes. This approach is vital for navigating the highly heterogeneous nature of leukemia across different age populations, from pediatric to older adult patients.

This interview has been lightly edited for clarity.

AJMC: What does research tell us about what triggers ALL and AML?

Bhatnagar: We’re not sure, although it’s one of the most common questions I get asked. Everyone wants to know why somebody got leukemia. The most common risk factor, which is similar for other cancers, too, is just increasing age. As we get older, our body’s ability to eradicate damaged cells becomes more compromised, and so these cells that should have technically been removed end up surviving, and not only do they survive, they multiply. That’s a very simplistic overview. But certainly aging is a risk factor.

We know that people who have had exposures to certain chemicals, radiation or occupational exposures like pesticides, people who work in labs and are exposed to a lot of chemicals, are also potentially damaging their DNA. That can also lead to development of these leukemias. We know also—we didn’t use to think this—but there’s also a hereditary component to acute leukemia as well. Over the past, say, 15 to 20 years, it’s become apparent that there are some inheritable leukemias as well. People essentially who were born with genes that could cause leukemia. These are all things that we take into account.

We also know that people who have what we call antecedent bone marrow disorders, like myelodysplastic syndromes and myeloproliferative neoplasms, they are also at risk for progressing to AML or ALL, as well as treatment for prior cancers. Because our treatments have gotten a lot better, patients are surviving their initial cancer diagnosis, whether it’s breast, lung, or colon, only to be at risk for blood cancers later on as a result of the chemotherapy they received. I think that’s why the field itself has shifted a lot, and we are moving away from these really intensive chemotherapy options across cancers in general. Hopefully we’ll be able to do that for all, if not the overwhelming majority, of cancers, and we won’t see these secondary leukemias occurring as a result of that

AJMC: How do ALL and AML present in adolescent/young adult patients vs older patients?

Bhatnagar: It depends. We know that ALL and AML are so heterogeneous in and of themselves. More commonly, I would say, particularly in AML, we see a good number of older adults presenting with lower white blood cell counts, as opposed to younger patients, who often present with higher white blood cell counts. Oftentimes, too, just based on my clinical experience, a lot of the younger AML patients tend to present in some ways sicker. They have a lot more reserve, and since the symptoms of both acute leukemias are nonspecific, and since both of them are also relatively rare in the cancer world, they’re easy to mistake for more common things. Either the flu or some type of a viral illness that you think is just going to shake itself off. Unfortunately, we see lingering symptoms and people get themselves checked out and have abnormal blood counts.

Those are the things that I’ve seen in my own clinical practice. A lot of my older AML patients tend to have a more indolent course. Oftentimes the AML or ALL diagnosis comes as a little bit of a surprise because they don't necessarily notice a whole lot of changes in how they're feeling. Those are some of the key differences, I would say.

AJMC: What are some of the factors you consider when risk stratifying younger and older patients?

Bhatnagar: We look at patient-related factors and disease-related factors. For patients, we look at their age. In the AML group, we draw a little bit of an arbitrary line in the sand that denotes older vs younger AML patients. A lot of that was done for clinical trial purposes. But in general, we tend to divide AML patients as older or younger than 60 years of age, and we do know that because disease biology differs according to age.

In the ALL group, we have a little bit more of a division based on age. We have pediatric ALL, which is really where ALL is more common. We see it very frequently in children, so pediatric ALL, and then you have older ALL, which is really 40 and above. Then the in-between ground, you have the adolescent and young adult population, which, according to the National Comprehensive Cancer Network, is characterized or defined as an ALL patient between the ages of 15 and 39. These are patients who kind of toe the line between pediatric and adult oncology, and they are considered their own subset of patients. Furthermore, we have the older-than-40 age group, and we also have people who are older than 60. We also know that the older you get with ALL, age is an independent predictor of worse outcome.

So we look at that, specifically age, and then disease characteristics as well. When we diagnose somebody with AML or ALL, we want to know the genetic underpinnings of their disease, so we check the chromosome abnormalities and the leukemic blasts, and that helps us stratify patients into favorable, intermediate, or unfavorable risk groups. We also look at the presence of certain molecular abnormalities as well because that can help us define how well somebody may do—how their leukemia is born essentially—and what it’s likely to do over time. Those are the main things that we look at when we're trying to risk stratify somebody with acute leukemia.