Karamjit Gill

Population-Based Analysis of Incidence and Outcome of Transformed Non-Hodgkin's Lymphoma

PURPOSE To assess the incidence and predictive factors for development of transformed lymphoma in a population-based series of patients with follicular lymphoma (FL). PATIENTS AND METHODS The Lymphoid Cancer Database was used to identify patients with FL diagnosed and treated in the province of British Columbia, Canada. Transformed lymphoma was defined as the development of aggressive non-Hodgkins lymphoma (NHL) in patients with FL. Factors present at the time of initial diagnosis of indolent NHL and at transformation were analyzed for their impact on risk of transformation and subsequent outcome. RESULTS Between 1986 and 2001, 600 patients with newly diagnosed FL met the inclusion criteria. With a median follow-up of 109 months (range, 10 to 244), 170 (28%) developed transformation, 107 (63%) based on biopsy confirmation. The annual risk of transformation was 3% continuously through 15 years. A multivariate analysis of clinical factors at diagnosis identified advanced stage as the only predictor of future transformation. The median post-transformation survival was 1.7 years. The 5-year survival was superior for patients with limited extent transformation compared with those with advanced cases (66% v 19%, P < .0001). Patients with transformation based on clinical versus histological criteria had an identical median survival of 1.8 years (P = .2). CONCLUSION The annual risk of transformation of FL is 3% continuing without plateau beyond 15 years. Advanced stage at diagnosis is predictive of future transformation. Clinically diagnosed transformation has an equal impact on outcome as biopsy proven transformation.

The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation.

Previous studies of follicular lymphoma (FL) patients treated heterogeneously have suggested that decreased numbers of regulatory T cells correlates with improved survival. We studied advanced-stage FL patients from a single institution phase 2 trial. All patients were treated uniformly with multiagent chemotherapy and radiation. Tissue microarrays were constructed using diagnostic biopsies available in 105 patients and stained with CD4, CD8, CD25, and forkhead/winged helix transcription factor 3 (FOXP3) antibodies. Both cell content and cell distribution were evaluated. For all antibodies, there were cases with a predominant intrafollicular or perifollicular localization of cells (follicular pattern) while others displayed a diffuse pattern. The median follow-up of living patients was 17.1 years. The International Prognostic Index score predicted overall survival (OS; P = .004) but not risk of transformation (RT). Cell content did not impact survival, while immunoarchitectural patterns of CD4/CD8 were significant for progression-free survival (PFS; P = .056), CD25 for both PFS and OS (P = .002 and P = .024, respectively), and FOXP3(+) predicted PFS, OS, and RT (P = .001, P < .001 and p = .002, respectively). A Cox multivariate model showed both International Prognostic Index score and FOXP3(+) pattern were independent predictors of OS (P = .008 and P < .001, respectively), while only FOXP3(+) pattern predicted RT (P = .004). We conclude that FOXP3(+) cell distribution significantly predicts survival and RT in FL.

CHOP-R therapy overcomes the adverse prognostic influence of BCL-2 expression in diffuse large B-cell lymphoma

BCL-2 protein expression correlates with shorter survival in patients with diffuse large B cell lymphoma (DLBCL) who are treated with CHOP chemotherapy. We report a retrospective analysis of the prognostic significance of BCL-2 status in patients who received CHOP with the addition of rituximab (CHOP-R) for DLBCL. Patients over 15 years of age with de novo, HIV negative DLBCL, without CNS involvement, and known BCL-2 protein status were identified from the BCCA Lymphoid Cancer Database. BCL-2 tumour positivity was defined as over 50% of tumour cells with BCL-2 protein expression. 140 patients who received CHOP-R were analysed. The majority (59%) of patients were over 60 years of age. Disease stage distribution was limited (22%) and advanced (78%). BCL-2 protein expression was observed in 90 (64%) cases. IPI score was similar in both BCL-2 positive and negative cases. Median follow-up time for living patients is 40 months. BCL-2 status did not predict for either progression-free or overall survival. IPI score was predictive for progression-free survival but not overall survival. The addition of rituximab to CHOP chemotherapy negates the adverse prognostic influence of BCL-2 protein expression on progression free and overall survival in DLBCL.