Prognostic Factors and Survival of Patients with Primary Mediastinal Large B-Cell Lymphoma.
Authors: Nowakowski Grzegorz S. , Kaur Prabhjot , Macon William R. , Habermann Thomas M. , Ristow Kay , Ansell Stephen M. , Witzig Thomas E. , Markovic Svetomir N. , Porrata Luis F. , Micallef Ivana N. , Johnston Patrick B. , Colgan Joseph P. , Inwards David J. 
Published: October 2019

Background: Primary Mediastinal Large B-cell Lymphoma (PMLBCL) is a biologically and pathologically distinct subset of large B-cell lymphoma of thymic origin. The natural history of PMLBCL is not well defined. While earlier reports suggested that PMLBCL is an aggressive disease with a poorer prognosis when compared to other large cell B cell lymphomas, recent studies report more favorable results. Some of the outcome variability reported in previous studies may be related to the inclusion of other pathological lymphoma subtypes involving mediastinum. Thus, we reviewed the pathology and clinical course of patients with PMLBCL seen at our institution.

Methods: We reviewed the biopsies on all patients diagnosed with mediastinal B-cell non-Hodgkin lymphoma (NHL) between 10/1983 and 10/2004. The pathological criteria for diagnosis of PMLBCL was a diffuse infiltrate of neoplastic CD20+ large B-cells within the mediastinum that frequently had "clear" cytoplasm and were often associated with fibrosis. We then reviewed the clinical data for patients with a pathological diagnosis of PMLBCL.

Results: 121 patients were diagnosed with mediastinal B cell NHL and had tissue available for review. Of these, 88 fulfilled the pathological diagnostic criteria for PMLBCL. The median age at presentation was 37 years (range 18–83). The male to female ratio was 1.06. Age adjusted IPI was: 0, 1, 2, 3 in 18%, 56%, 18% and 8% of the patients respectively. The most commonly used treatments were: CHOP (70%), R-CHOP (22%) and ProMACE-CYTABOM (6%). 62% of the patients received adjuvant radiotherapy. 24% of the patients received high dose chemotherapy with autologous stem cell transplantation (2 patients in first remission). The median follow up was 66 months. The 2 and 5 year survival was 72% and 68% respectively. On univariate analysis, age >60 (p=0.012) and presence of B symptoms (p=0.0094) were associated with an adverse outcome. On multivariate analysis, only the presence of B symptoms (p=0.039) was an independent predictor of shortened overall survival. The 2 year survival of patients with age adjusted IPI of 0–1 or 2–3 was 86% and 68% respectively (p=0.023). Patients treated with adjuvant radiation therapy had a 5 year survival of 74% versus 53% in patients who did not receive adjuvant radiation (p=0.042). However, there was a higher percentage of Ann Arbor stage 3 and 4 disease patients found in the group who did not receive radiotherapy treatment (66% vs 17% respectively).

Conclusions:

The overall survival rates seen in patients with a confirmed pathological diagnosis of PMLBCL were superior to that reported in earlier studies and similar to that reported with the use of more intensive chemotherapy regimens. While many authors report a high proportion of female patients with PMLBCL, we did not observe any gender differences. While patients receiving adjuvant radiation therapy had a better outcome than those that did not, the retrospective nature of this study and differences in stage distribution preclude conclusions regarding the role of adjuvant radiation therapy. Randomized studies will be necessary to assess the optimal treatment for PMLBCL.