Second malignancies among Waldenstrom macroglobulinemia patients: small samples and sparse data

Abstract

We read with interest the analysis by Varettoni et al. [1], which provides initial evidence regarding second malignancies among Waldenstrom macroglobulinemia (WM) patients. The authors compared incidence rates of various second malignancies among WM patients in north Italy to the incidence rates of corresponding primary malignancies among the general population of north Italy after standardization for age and sex. The standardized incidence ratios (SIRs) from this comparison indicated increased relative risks of diffuse large B-cell lymphoma (DLBCL), myelodysplastic syndrome/acute myeloid leukemia, and brain cancer. Nonetheless, we encourage conservative interpretation of these SIRs because of a small sample (N = 230) and sparse data (only two of the evaluated malignancies had more than five observed cases). The consequence of these limitations is lack of precision [e.g. the confidence limit ratio [2] for the SIR of brain cancer is 16, suggesting a highly imprecise estimate] and potentially upward biased estimates [3]. Therefore, we explored the consistency between SIR estimates from the Varettoni et al. [1] analysis and SIR estimates from a larger WM population.