Personalized Selection of Upfront Therapy in CLL - Episode 17
Susan M. O’Brien, MD: CLL is the most common leukemia in the Western world, and it accounts for about 30% of adults with leukemia. And it’s only seen in adults; it’s not a childhood disease. The etiology is really not very clear. One of the etiologies that we do know of is exposure to Agent Orange, but obviously that’s a minority of patients who develop CLL. So, for the most part, we are not clear on what causes CLL to develop.
CLL is a little bit of an unusual leukemia in the sense that we don’t actually have to do a bone marrow to make the diagnosis. And that’s because we can take advantage of flow cytometry by sending a peripheral blood sample for flow cytometry and getting that classic phenotype that we get for CLL; namely, the presence of B-cell markers because it is a B-cell disease, but also the simultaneous presence of CD5, which we normally think of as a T-cell marker. If we want to determine mutation status on patients, again, that can be done also from the peripheral blood. We do not need to send a lab for sequencing of the IGHV gene.
An important prognostic factor in CLL is determined by the FISH panel that we use, and that typically detects for common abnormalities in CLL: trisomy 12, 13q minus, 11q minus, and 17p minus—so, deletions. There is some value to doing standard cytogenetics, because data have emerged that another prognostic factor is complex karyotype. So, if the patients have a complex karyotype, that confers a very poor prognosis. And that can be done from the blood with decent yield. Sometimes you do get a better yield from the bone marrow, but because otherwise we don’t generally need a bone marrow, we can send cytogenetics from the peripheral blood and do a standard FISH panel.
There is just 1 association between mutation status and a specific chromosomal abnormality. In other words, patients, even with the worst prognosis—chromosomal abnormality of 17p deletion—can have a mutated or unmutated IGHV gene. The 1 where there’s a very tight correlation is 11q minus. So, 11q deleted patients, about 90% of the time, are unmutated, and that confers a poor prognosis. This is due to the fact that they’re unmutated, but in addition, the fact that they’re 11q deleted confers even more of a poor prognosis in general with chemotherapy, although that may be changing with some of the newer targeted therapies.