So peripheral T cell lymphoma is a fascinating, uh, condition. It's a relatively rare condition, so it accounts for approximately 10% of non-Hodgkin lymphomas that we see. And overall, certainly in the UK, uh, lymphoma is the fifth commonest cancer. The other thing that really is fascinating about T cell lymphomas is it's not only rare, but there are lots of different subtypes that are now identified. So of course, each of those is even rarer. The commonest subtype, certainly traditionally is peripheral T cell lymphoma NOS or not otherwise specified. Now obviously that's, uh, sounds like a bit of a sort of dustbin diagnosis. It sort of is really. It's what's left when all the other subtypes are ruled out. Uh, and the second commonest subtype is something called angioimmunoplastic T cell lymphoma. Uh, the third commonest being, uh, anaplastic large cell lymphoma, which itself is split into a positive and a negative populations, uh, or out positive and negative subtypes. So those are the three that we tend to see most commonly of the peripheral T cell lymphomas. Um, and what's happened over the last few years though is it's become increasingly recognized that particularly the angioimoblastic group is probably bigger than we first thought. And really the clue there came from dissecting out the PTCL NOS's, having careful pathological sort of look backs, and there was a group that didn't quite meet the criteria for being AITL, angioplastic T-cell lymphoma, but had some AITL-like features. This was coupled with gene expression profiling, which showed that amongst the PTCL NOS's there was a certain group that seemed to have a gene expression profile, um, or rather a mutation analysis actually similar to, uh, AITL angiomenoblastic T cell lymphoma. So this has led to the concept of actually splitting T cell lymphomas into those that are derived from the T follicular helper cell, because that's the cell of origin for the AITLs versus non TFH derived T cell lymphoma. And that's really led, if you like, to an expansion of the AITL group. Now there are actually. Uh, you know, we don't call them all AITLs, um, there are other specific subtypes that fall into the TFH category, but actually having that division of TFH and non-TFH is actually quite, uh, convenient now. Now, what does TFH mean? How do we sort of define TFH? Well, it's really based on the immun to chemical markers. That a pathologist will apply when they're doing the diagnostics, in particular, uh, markers such as PD1, such as CD10, such as BCL-6, such as ICOS, um, these are all TFH, uh, markers, and once you have more than 2, then we can define it as a TFH derived T cell lymphoma. Now one thing that characterizes all of these T cell lymphomas is that their prognosis is relatively poor compared to B cell lymphomas, apart from maybe one or two very uncommon subtypes such as ALK positive ALCL. Traditionally we treat with chop chemotherapy, so that's 4 drugs, uh, cyclophosphamide, doxorubicin, vincristine and prednisolone. Uh, we give it every 2 to 3 weeks, uh, up to 6 cycles, and this was really developed before we could tell the difference between B and T cell high grade lymphomas. And then when in histochemistry. Developed and you could tell the difference between the two. B cell lymphomas were sort of taken out as the more common entity, and rituximab, the anti CD20 monoclonal, was developed. So our CCHOP became standard for B cell lymphoma, and that was associated with a significant, um, both progression free and overall survival compared to CHOP. Whereas T cell lymphoma, we've never had a similar sort of rituximab-like moment. So we, we're really stuck with COPP. And chop really for all PTCL may be cures, and I do use the word cure, we do cure some people with PTCL, but maybe around the 30 to 40% mark. Now some people in a bid to sort of improve that added a top aside, so called COEP. That was data from the German group. But actually, um, you know, there's no randomized control data to suggest that actually we're doing any better with the toposide. So certainly my practice is um to stick with COPP. And then there was the addition of Brenttuximab thedotin to some cases, that's an anti CD30 monoclonal. If you do add that, you need to drop out the vincristine so it becomes BV chip. And that's been licensed in the US for all CD30 positive uh peripheral T cell lymphomas. However, in Europe, it's restricted to anaplastic large cell lymphoma, and that's based on the Echelon 2 study that showed a PFS and initially an overall survival of BV chip compared with CHOP, uh, in CD30 expressing T cell lymphomas. But that group was enriched for anaplastic large cell lymphoma, hence the European and UK license, as opposed to the FDA license. And then the other controversy in the frontline treatment of peripheral T cell lymphoma is whether we take patients who are fit enough to an autologous stem cell transplant. Um, there's various retrospective studies that suggest it may benefit patients, but that of course is fraught with, with bias, um, in that we might be autographing the fit patients and, uh, not autographing the unfit patients. That the data that convinces me a little bit more is population data, where you can roughly sort of match for patients who did and didn't have an autograph, and some of that population data at least suggests a benefit, albeit the data from the French group suggests there is no benefit. So it's still a rather controversial. Uh, um, discussion point whether we should be autografting PTCL in first remission. Um, I have to say my practice is I do tend to do that unless it's an out positive, uh, ALCL.
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