How do you approach previously treated grade 1 follicular lymphoma now with transformation to a large cell lymphoma?

I believe the question is an important one that has not been addressed by an adequately powered prospective study. These patients are often folded into studies of relapsed and refractory disease. The consensus is that these patients have a poorer prognosis than those with de novo diffuse large B-cell lymphoma but all of us who manage these patients have a group who have been cured after histologic transformation. My biased view is that dose-adjusted EPOCH-R provides the highest chance of achieving a durable remission. I have not been convinced that high-dose therapy with autologous transplant is more effective as the first treatment and I tend to reserve that approach for the first relapse of transformed lymphoma, if needed.