Risk Assessment in ALL

James K. McCloskey, MD: Hello, I'm James McCloskey. I'm the chief of leukemia here at the John Theurer Cancer Center in Hackensack, New Jersey.

Ibrahim Aldoss, MD: I’m Ibrahim Aldoss. I'm an associate professor in the department of hematology and hematopoietic cell transplantation at City of Hope [City of Hope Comprehensive Cancer Center,Duarte, California]. I'm specialized in adults and AYA (adolescent and young adult) acute leukemia and transplant. Today, we'll be discussing acute lymphoblastic leukemia (ALL) with the focus on B-Cell ALL and the treatment approach for children, adolescents, and young adults. And I will start by asking Dr McCloskey about the risk assessment in B-Cell ALL and discuss the classification and how this can impact the treatment, the prognosis, and after-treatment in this patient population.

James K. McCloskey, MD: The risk assessment strategies have shifted, particularly as we consider the role of MRD [minimal residual disease], which I'm sure we're going to talk about a lot today. Historically, we have often used a variety of techniques to risk-stratify patients, and we know that this is a heterogeneous disease, maybe not so much as AML [acute myelogenous leukemia], but we always attempt to look at a patient's age. Certainly, as we're going to discuss today, age is an important variable in considering a patient's disease biology. We certainly know that adults behave differently than adolescents, and even adolescents are different from the true pediatric population. Historically, we've often used a high white blood cell count. Again, I don't know that that's as important today in the MRD setting. We continue to use sided genetics, and particularly MLL [mixed-lineage leukemia] rearrangements are important to look for and prompt a referral for transplant for us. And then molecular testing, particularly in the AYA population, and identifying those patients with Ph-like ALL (Philadelphia chromosome-like acute lymphoblastic leukemia) is important to identifying those folks and as a higher risk patient population for relapse and considering the role of transplant.

Ibrahim Aldoss, MD: I agree with you, James. It's an important part when we have a newly diagnosed ALL patient. Genetics continue to play an important role in stratifying patients, even in the presence of the MRD and the MRD assessment. And as you pointed out, Ph-like ALL is an important subtype that is unfortunately still underdiagnosed, especially when the patient is treated outside large academic centers, because truly, there is no consensus on how to diagnose Ph-like. But as you pointed out, it's not uncommon in CT [computed tomography]. What we see is up to 20% of cases with B-Cell ALL. And it has implications because these patients don't do well like other subtypes of B-Cell ALL. And unfortunately, the TKIs [tyrosine kinase inhibitors] that are available for the high-risk Ph-positive ALL doesn't work as well in this subgroup. It is important. And as you mentioned, age is important because part of it is the biology of the disease is different. We see good risk genetics in younger patients or we see more hyperdiploid translocation 1221, while older patients, they tend to have high-risk genetics such as Philadelphia chromosome MLL, as you pointed out. That's part of the age, how this influences the prognosis of ALL. But besides that, besides the biology, older patients tend to tolerate treatment not as well as younger patients, even if they have the same genetics. And this leads to early discontinuation, delaying therapy, in addition to the psychosocial issues in adults compared to pediatric, where they have more frequent instruction in the therapy.

Transcript Edited for Clarity