Late Relapse of Localized High-Grade Non-Hodgkin’s Lymphoma: Clinical and Biological Features
Authors: Damaj Gandhi , Bernard Marc , Legouill Steven , Cartron Guillaume , Le Mevel Annie , Dubus Céline , Berthou Christian , Colombat Philippe , Milpied Noel , Marolleau Jean Pierre , Lamy Thierry 
Published: April 2020

Abstract
Diffuse large cell lymphoma is the most common non-Hodgkin Lymphoma (NHL) that ranks among the most curable diffuse intermediate grade lymphomas. Most investigators have recognized that practically all patients with this cell type who are able to attain and maintain a complete response for 24 consecutive months are cured because late relapses seldom occur after this period of follow-up. However, relapses do occur late after the remission and the characteristics of patients who experience these relapses rarely have been studied especially for localized disease. From 1984 to 1996, three hundred and five patients aged more than 18 years were enrolled in a prospective multicenter study for primary treatment of localized stage I/II nodal and extra nodal high-grade NHL. The initial therapy consisted in three cycles of high dose CHOP regimen followed by involved field radiotherapy (40Gy). Of the 283 (93%) patients who obtained complete remission (CR), 36 (12.7%) patients relapsed more than 2 years after CR and 28 (9.8%) of them experienced relapse more than three years after CR. Clinical characteristics of patients at diagnosis are summarized in table 1. For the 28 patients who relapsed more than 3 years after diagnosis (group A), the median age was 55 years. There were 17 men and 11 women with predominant histology of diffuse large B cell lymphoma (n=15) and mixed small and large B-cell (n=6). Stage I disease was predominant (n=16) with normal LDH level (n=14). Extranodal disease was present in 11 patients. Most of the patients had no or one IPI risk factor at diagnosis (n=18). Relapses occurred after median CR duration of 84 (36–156) months. Seven patients (7/28; 25%) relapsed as a disseminated lymphoma and 17 of 21 patients who relapsed as a localized disease, relapsed at sites other than those of diagnosis. Only 4 patients relapsed at the same initial site of lymphoma. Nodal relapses remained the most frequent type of relapse (n=18; 64%). However, it is important to note that 10 patients experienced extranodal relapses especially in the central nervous system, the Waldeyer’s ring and the gastrointestinal tract. Three patients had multiple extranodal localisations. All relapsed patients received chemotherapy alone (n=20) or followed by autologous stem cell transplantation (n=8). CR was obtained in 13 patients (13/23; 56%), and partial response in 1 patients. Chemotherapy failed in 5 patients and 4 patients deceased from toxicities. At the last follow-up, only 8 (8/24; 33%) patients are still alive and disease free (n=5) or in relapse (n=3). Sixteen patients deceased and lymphoma was the most frequent cause of death (13/24; 54%). In conclusion, late relapses in the setting of localized high grade NHL treated with short course of chemotherapy and involved field radiotherapy are frequent. Relapses occurred frequently at different sites from the initial presentation mostly nodal and extranodal localisations are frequent. The rate of cure for relapsed patients is low and death from lymphoma remains high. The role of novel therapeutic approaches with the addition of rituximab to chemotherapy with or without radiotherapy in preventing late relapses is awaited. More data will be presented at the meeting
Table 1: clinical characteristics at diagnosis