Relapse from Complete Remission More Than 5 Years after Therapy for Diffuse Large B-Cell Lymphoma (DLBCL): Relapse Histology Most Commonly DLBCL with a Germinal Center B-Cell (GCB) Phenotype.

Although many patients are successfully treated for DLBCL, relapses can occur especially in the higher risk patients. Relapses in successfully treated DLBCL patients most frequently occur within the first 2–3 years. However in a small number of patients, relapses occurring after 5 years do happen and have been frequently reported to be a relapse of follicular lymphoma. We evaluated 805 patients with DLBCL treated with an anthracycline based chemotherapy through the Nebraska Lymphoma Study Group from 1983–1998. The patients were treated prior to the use of rituximab in this patient population. Two hundred and three patients relapsed from a documented complete remission. Of these, 30 (15%) relapsed more than 5 years after treatment (range 5.3 – 14.5 years, median 6.8 years). The median age at relapse was 71 years (range 32 – 85) and 58% were male. Patients with late relapses had relatively good prognostic features at the time of diagnosis. None had a low performance status, 71% were stage I/II, 78% had no systemic symptoms, 78% had a normal LDH, and 67% had an IPI of 0/1. All patients had biopsies to document relapse. Eighty one percent of the relapses were documented DLBCL, 11% had composite lymphoma with DLBCL and follicular grade 3 (FL3) lymphoma, 4% had FL3 alone, and 4% had follicular grade 1 (FL1). Using immunohistochemistry to predict GCB vs. non-GCB origin, 72% of the patients had a GCB phenotype at diagnosis and 90% had a GCB phenotype at relapse. Four patients had no therapy at relapse and 2 patients had radiotherapy. The remaining patients received a variety of combination chemotherapy regimens with or without rituximab and 2 patients underwent autologous stem cell transplantation. Seven patients had durable complete remissions to their second line chemotherapy regimens (4 with chemo + rituximab and 2 autologous stem cell transplantation). Three of these survivors died of unrelated causes and 4 are alive in remission 19–119 months after the salvage therapy or autologous transplantation.

Conclusions: Most patients with late relapses of DLBCL initially present with good prognostic characteristics at the time of the origninal diagnosis. Unlike previous studies, the most common type of histology in this study at the time of late relapse was DLBCL and not follicular lymphoma. However, the vast majority of the late relapse DLBCL patients had a GCB phenotype both at diagnosis and at relapse. Patients with late relapses usually do respond to salvage therapy and can have second prolonged remissions with chemotherapy and/or autologous stem cell transplantation.