Signs and Tests for Diagnosis and Prognosis of HCL

Jae Park, MD: What other testing should we be performing when you see a patient who has a suspected diagnosis or clinical presentation of hairy cell leukemia? I’ll start this section with Andrea.

Andrea Sitlinger, MD: The first part of the diagnosis after you've had your CBC [complete blood count] with differential and taken a look, is a bone marrow biopsy. Often it is extremely difficult or impossible to get an aspirate, and that's due to the fibrosis that's induced with the hairy cell as well as probably some interlocking of those hairy cells with the projections. It's important that you still attempt it. But still you'll get a good biopsy to then look under the microscope. You'll see the classic fried egg appearance that still comes up on boards for many people, and it's usually a hypercellular marrow. There is a percentage, less than 10%, of hypocellular marrows that coexist, but it's usually hypercellular. We were just talking a lot about BRAF testing. I will note it has not been incorporated as an NCCN [National Comprehensive Cancer Network] automatic diagnostic criteria, but I think most of us find it's important. One, because it will help if there’s any question with the immunohistochemistry to classic variant vs other variants of hairy cell. It also potentially does guide treatment down the road.

Beyond the BRAF testing, the other thing that's important is your immunohistochemistry testing. Classically, I'm sure we all have seen variants, hairy cell is pan-B cell antigenic expression, CD19, CD20, CD22. And importantly, in distinguishing from other indolent lymphomas, it lacks CD5, CD10, CD23, and CD27, also CD21. CD103 is a very sensitive marker for hairy cell, and classically you have CD11c and CD25. Immunohistochemistry testing is extremely important. Another thing that comes up is when to do imaging, and I open that up to the rest of the panel, but it's certainly not necessary. If you have questions about the spleen or if other things are going on, you’re palpating lymph nodes and you're wondering, it can be useful, but imaging is not a mandatory aspect of the hairy cell diagnosis.

Alan Saven, MD: I agree. I don't routinely do CT scans or ultrasounds of people's abdomens. If the patient’s on a clinical study and you want to know the depth of response, I think it's a necessary step to do to see if you can resolve splenomegaly. About 20% of patients will have lymphadenopathy on CT scan, but in terms of routine care of patients, I don't see any advantage, especially if you can palpate the spleen. Even if you can’t palpate the spleen, I'm not sure it moves the ball very far forward to be able to know whether there’s imaging of a spleen. It's not clinically significant.

Jae Park, MD: Dr Saven, you spoke about the prognosis of the patients with hairy cell leukemia. We spent time on clinical presentations and diagnostic work-ups. When we see them, is there anything that we can share with our patients that you know about how they are likely going to do in terms of the genetics, clinical age, or anything you consider?

Alan Saven, MD: The first thing I tell the patient is, “You've got the best of the bad bunch, and your life expectancy is very close to that of the normal population.” Despite the rarity of this disease, there’s a plethora of treatments. Hematologists are squabbling about what's the best of the combination of drugs and which is the least toxic. The overwhelming majority of patients seem to do very well. If you're on the younger side, below 40, when you get the disorder there seems to be a slightly more aggressive nature to the disorder, but it’s still very indolent. If your flow cytometric pattern doesn’t express all the markers that Andrea alluded to, is CD25 negative, but you got everything else, you may not do as well as everybody else. If you’re BRAF negative as opposed to BRAF positive, it may be that you don't have typical hairy cell leukemia and you’re not expected to do as well. We spoke about the MAP kinase expression. They tend to do worse. If you’ve got the VH4-34, they tend to do worse. The size of your spleen, severity of your cytopenias, tend not to affect your prognosis. Patients who present with typical or atypical hairy cell leukemia who have a high white count tend not to be as sensitive to the purine nucleoside analogues. But the overwhelming majority of patients do exceptionally well and can expect a near-normal life expectancy.

I don’t know if second malignancies is a topic for discussion today, but the incidence is increased. There was a long debate as to whether it's treatment related because the drugs are very immunosuppressive, or whether it's the disease itself, or combinations of the above. Often patients get second malignancies 10, 20 years later, and that's actually the cause of their demise.

Steven Coutre, MD: How do you frame the conversation with the 35-year-old with hairy cell leukemia? They're looking at a horizon of about 50 years.

Alan Saven, MD: Let’s start with, “You should do very well. You’re going to become an expert on this disease. You’re going to read all the articles. Your disease may be a little bit more aggressive.” We haven't gotten to treatment yet, but I tend to give them combination therapy with a purine nucleoside and an anti-CD20, just so I can try to get closer to minimal residual disease. They tend to do very well despite the young age, but you're right, they want to know what's going to happen when they are 60, 70 years old. They should do well, but not necessarily so because we don't have a curative approach. We don't think that we can cure this disease, even with all the therapies available, so at some point they're going to relapse.

Transcript Edited for Clarity