Individuals diagnosed with mantle cell lymphoma (MCL) demonstrate substantial diversity in both their clinical manifestations and long-term prognosis. Nevertheless, the prognostic tools currently in widespread use are outdated and fail to meet the requirements of modern multidisciplinary care for this malignancy. The current investigation aims to characterize the clinical and pathological features of MCL in the context of immunochemotherapy and to develop enhanced prognostic tools that more reliably predict patient outcomes. The North American Mantle Cell Lymphoma Project constitutes a collaborative effort across 23 institutions in North America dedicated to assessing and optimizing prognostic factors for initial treatment. This analysis encompasses 586 cases of MCL diagnosed from 2000 to 2012. An extensive retrospective review examined clinicopathological characteristics, therapeutic interventions, and survival endpoints. Novel prognostic models were formulated following detailed evaluation of pretreatment variables and were subsequently tested for validity in a separate, independent group of MCL patients. In frontline treatment regimens, hematopoietic stem cell transplantation was the predominant determinant of clinical endpoints, exerting highly significant effects on both overall survival (OS, P < 0.0001) and progression-free survival (PFS, P < 0.0001). Among pathological markers, p53 expression emerged as the strongest predictor of unfavorable prognosis (P < 0.0001 for OS and P = 0.0021 for PFS). Using baseline risk profiles, we constructed several prognostic models that combine clinical, laboratory, and pathological features, each designed for a specific clinical context. These models demonstrated excellent discrimination in the independent validation set and produced risk groupings that closely mirrored those in the derivation cohort. Survival rates among patients with MCL have improved considerably during the last twenty years, and continued progress is expected as therapeutic approaches advance. The newly proposed prognostic models presented here represent a useful resource for tailoring treatment selection to individual patients with MCL.
