Prognosis in Chronic Lymphocytic Leukemia

To the Editor: The review “Predicting Prognosis in Chronic Lymphocytic Leukemia in the Contemporary Era”¹ summarizes the modern understanding of how the outlook for patients with the most common leukemia in the Western hemisphere can be predicted by exploiting molecular achievements. Unfortunately, a prognostic value of molecular aberrations, if applied outside a clinical context, continues to be unreliable and may be easily misperceived. Chronic lymphocytic leukemia (CLL) may surprise by taking an unpredictable path with no regard to its genetic defect(s). The authors’ upfront statement that “patients with 17p13.1 deletion have poor response to chemoimmunotherapy and are treated differently” echoes the pervasive notion that 17p- signifies a more aggressive form of CLL. However, this statement is misleading. A number of patients with CLL with 17p- enjoy an indolent course² in which any form of therapy, especially aggressive, will be disadvantageous. Despite the authors’ citation that “there is a clinical heterogeneity in patients with 17p deletions,” this fact is never sufficiently emphasized (see their Figure 2). As a result, the most crucial practical point is missed: that a 17p- CLL is not always ominous, and it may not necessitate chemoimmunotherapy. The National Comprehensive Cancer Network guidelines³ also blend all CLL patients with 17p- anomaly together on the basis of a low response rate to immunochemotherapy, thus exaggerating a pessimistic outlook of this cohort. Most importantly, the guidelines lack the affirmation that not only is it acceptable, but actually prudent, to avoid the treatment even for potentially “high risk” patients if the disease remains silent. European patients with CLL evidently benefit from a more explicit (and judicious) recommendation: for asymptomatic patients, molecular studies are irrelevant because the first line of treatment for this category of patients is nonexistent.⁴