At the outset, when making the diagnosis of MCL and developing the plan, it is important to be sure that the diagnosis has been reviewed by an expert in hematopathology. The diagnosis of MCL can be subtle, and risk stratification can be even subtler (eg, if a patient has been diagnosed as having the blastoid variant of MCL, expert review is particularly important). MCL is quite heterogeneous, and early risk stratification is a useful tool for clinicians who commonly treat patients with MCL. Early risk stratification can help to identify the small but significant subset of individuals with newly diagnosed MCL who have indolent disease and can be safely managed with observation for approximately 1 year. These patients may be identified at diagnosis by a low Ki-67 proliferation index and a low Mantle Cell Lymphoma International Prognostic Index (MIPI) score. 

Risk stratification by MIPI score into low-, intermediate-, and high-risk groups is also useful for comparing clinical trials (ie, based on the proportion of low-, intermediate-, or high-risk patients enrolled). For the clinician who does not commonly treat patients with MCL, risk stratification is perhaps a valuable tool to gain a general understanding of a patient’s level of risk. However, the individual risk factors that comprise the MIPI are not extremely valuable for making clinical decisions or selecting therapy for any individual patient. In addition to the MIPI, molecular markers have a limited role but may be important in certain cases, such as in patients with TP53  aberration. Those with TP53  aberration have worse outcomes and do poorly with chemotherapy. In these individuals, I might be more inclined to use a more targeted therapy at some point earlier in their disease course; these are also patients for whom I might consider an allogeneic stem cell transplantation, which is performed much less commonly in the modern era. Complex karyotype is another important prognostic factor that predicts inferior survival. 

We have made a great deal of progress in risk stratification, but MCL remains an incurable disease with no established standard of care. For this reason, all patients with MCL who require treatment should be considered for enrollment in clinical trials in both the upfront and, perhaps, relapse settings, particularly those patients with high-risk MIPI scores.