Edited excerpt from the discussion:

DR SMITH: This is clearly an area that’s in a state of flux. Typically, in the working formulation, follicular large cell or what we now call follicular Grade III was considered an intermediate grade. We would have given R-CHOP based on the large cell data, which is probably not a bad idea; however, her disease is behaving a little more indolently.

If you review the literature on follicular large cell from over the years, Stanford published a paper in which they defined follicular large cell lymphoma as more than 50 percent large cells. According to the Nebraska data, follicular large cell lymphoma looks more like follicular Grade I and II. Patients in Nebraska are diagnosed with follicular large cell lymphoma a lot more often than patients at Stanford because they use more of the so-called formal criteria.

Follicular Grade III is probably a mix of diseases. People have tried to divide it into follicular Grade IIIA and B, with the A being a mixture of small and large cells, and the B being sheets of large cells. The IIIA/IIIB distinction has not been formally demonstrated with prospective data but it makes intuitive sense.

This is a long-winded prologue to saying that you can give R-CHOP and say, “Well, it’s not a bad treatment for low grade lymphoma. It’s a good treatment for aggressive lymphoma, and we won’t be undertreating her.”

If she’s had this node for a long period and the gallium is negative, then you might do a PET scan to convince yourself that no areas of high uptake exist, in which case you might be comfortable in watching and observing the pace of the disease. I think you could go either way. It’s sort of a gestalt, and the patient may need to be involved in the discussions by telling her, “Here’s what we know. Here’s what we don’t know.” R-CHOP would be a good therapy for either of these. I think the ultimate prognosis — whether you have a curable disease — is still up in the air.

DR LEONARD: In aggressive lymphomas, I’m a big fan of the International Prognostic Index (2.1). I sit with the patient and go through their IPI risk factors and tell the patient what their chance of cure is. Now that the follicular lymphoma IPI (2.1) has come out, I think we know less about what to do with a patient with a bad- or good-risk FLIPI; however, I think it’s a good idea to at least go through it.

The FLIPI, or the five criteria that were established based on a group of about 4,000 patients, was published in Blood in September 2004. The five factors are described by the acronym, NoLASH: (1) more than four nodal areas; (2) elevated LDH; (3) age greater than 60 years; (4) Stage III or IV; and (5) hemoglobin level less than 120 g/L (12 g/dL). [Leonard JP. Blood 2004;104(5):1233-4]. Based on what you said, this patient has two of the five factors.

The point is that if she has three of the five factors, the five-year survival rate is about 50 percent. We don’t know whether or not treating those patients differently or more aggressively is going to help things, but if that’s the case, then we’re not necessarily doing her a favor by holding off on therapy. If you think about it, a 50 percent five-year survival rate is poor.

So how do we act on that? We don’t know. We need randomized trials to evaluate whether or not patients at high risk who are treated with a specific regimen do well or don’t do well. I’m hoping that all of the up-front regimens that are being tested and have been tested will evaluate this retrospectively so we can determine whether a given regimen works well in patients at high risk versus patients at low risk. My point is that she doesn’t fall in the best-risk group. She may well be in the worst-risk group and, if so, I would consider more therapy.

The question is: What is a little bit more? R-CHOP as an up-front regimen is at the stronger end of the spectrum. We have good data with that regimen, and randomized trial data indicate some benefit. Whether that is the answer for patients with high-risk FLIPIs, we don’t know at this time. We haven’t seen those data.

Given this patient’s young age, the options of investigational trials and transplant — whether it is autologous or allogenic — may move up the list because she has some adverse factors. I agree with everything that Mitch said, but I would reiterate that based on the prognostic factors, this may not be a follicular lymphoma that putters along for 10 years. This patient may require additional treatment relatively soon and, therefore, you work your way down a treatment list relatively rapidly.

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