Up to one third of patients with mantle cell lymphoma (MCL) may be observed for a period of months to years before developing indications for therapy. Importantly, observational studies suggest that this approach has no apparent negative impact on their overall survival. Although there is broad agreement on which patients require early therapy, identification of patients with less aggressive disease can be challenging. Clinical tools such as the Mantle Cell International Prognostic Index (MIPI) and Ki67 are effective at predicting survival but may not always correspond with indications for treatment. Research tools such as the proliferative signature are attractive but have yet to be evaluated in this context. Physicians, therefore, must make decisions regarding therapy based on the best available evidence. In the absence of evidence that treatment necessarily influences long-term survival, it may be reasonable to observe selected patients for a period of time prior to making definitive treatment-related decisions. Collaborative efforts are required to better understand the pathophysiology of the disease and potentially identify patients amenable to "watch and wait." Similarly, patients with less aggressive MCL may be an ideal group in which to evaluate novel treatment approaches.
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