September 21, 2018 / All Stories

Seeking a missing acronym in CLL

As our ability to detect smaller amounts of cancer increases, so does the hope for a better future for CLL patients.

A “good” cancer

As a practicing physician at an academic medical center, John Hayslip, M.D., taught students and fellow physicians about the differences between blood cancers. Whenever he would introduce the topic of chronic lymphocytic leukemia (CLL), he’d hear a common refrain.

“People would say, ‘ah, CLL… that’s the good cancer to have, right?’” Hayslip says, now a medical director at AbbVie. “Or, ‘that’s the one where you die with the disease, you don’t die because of the disease.’”

Hayslip would explain to his colleagues that CLL, while not rapidly fatal, is indeed a serious disease that tends to reoccur even after repeated remissions – with treatment becoming more of a challenge with each subsequent relapse.

The missing acronym

The complexity of treating CLL is best spelled out through another acronym: MRD. This stands for minimal residual disease, an objective measure of disease defined by a certain number of leukemia cells found in white blood cells.

For patients with other types of blood cancer like acute lymphocytic leukemia (ALL) and chronic myeloid leukemia (CML), the MRD acronym has been part of the lexicon since technology evolved to be able to detect submicroscopic amounts of cancerous cells.

“It’s a measure beyond what we had in the past,” Hayslip explains. “Before we could test for MRD, a patient could go into what we call complete remission, where you couldn’t detect any more signs of cancer in the peripheral blood. But we knew there were probably still cancer cells running around in the patient’s body, and we just had no way of detecting them.”

As technology advanced from less-sensitive measures like CT scans to tests that gave the ability to pick out one leukemic cell out of 10,000 in a blood or bone marrow sample, MRD testing became important in clinical practice. But often for patients with CLL, the concept of MRD was missing in action.

“From my perspective, the reason we didn’t used to talk about MRD as much with patients with CLL is because the most you could hope for was getting to the point where the cancer was hard to detect under a microscope,” Hayslip says. “And no matter what the test result, we had a finite number of options to offer patients, and we had to be perpetually thinking about the next relapse.”

Blood smear of chronic lymphocytic leukemia (CLL), analyzed by microscope. (photo credit: Shutterstock)

An end in sight?

Like two highways converging, the technology that would allow for more specific measures of MRD and the understanding of CLL are on a parallel trajectory. MRD negativity in CLL is now defined as having blood or bone marrow with less than one chronic lymphocytic leukemia cell per 10,000 leukocytes (white blood cells).

The evolution of techniques like an antibody test called flow cytometry, and ASO-PCR (allele-specific oligonucleotide polymerase chain reaction) which identifies DNA sequences unique to a patient’s CLL cells, have increased the ability to measure this in patients.

At the same time, oncology researchers like Hayslip are discovering new opportunities that may one day make CLL the “good cancer” it’s rumored to be.

“We now know the goal for CLL includes eradicating all the leukemic cells you can find, and doing so in a way that is safe for the patient,” Hayslip says. “We are getting closer to finding protocols that may one day help doctors to tell patients they can stop treatment, and go on with their lives. A decade ago, it was hard to imagine this as a possibility.”

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Carlos Taveras
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