Risk of Second Malignant Neoplasm Among Patients With Lymphoma

Abstract

TO THE EDITOR: The recently published article, “Long-Term Complications of Lymphoma and Its Treatment,” by Ng et al 1 provides a much needed overview of its topic. Unfortunately, however, the article fails to emphasize two key concepts: first, the necessity of investigating the impact of associated rituximab treatment in nonHodgkin’s lymphoma on long-term complications, and second, the differences in risk of a new, second malignancy caused by a lymphoma subtype. Briefly, the monoclonal antibody rituximab has increased disease-free survival for many lymphoid malignant diseases and seems not to have a significant influence on secondary myelodysplastic syndromes/acute myeloid leukemia, whereas it has emerged as an independent risk factor for solid tumor development. 2 In addition, even if the precise role played by B cells in cancer biology remains to be defined, recent reports stress antitumor B-cell— derived immunity. 3,4 In other words, it seems conceivable that the profound immunosuppression that is secondary to B-cell deletion by rituximab may contribute to the expansion of tumor cells. Given that the occurrences of lung cancer and melanoma are limited to more indolent lymphomas, it is plausible that long-term immune dysfunction from the underlying disease or repeated treatments is responsible. Furthermore, the heightened risks immediately after chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and follicular lymphoma (FL) diagnoses suggest an intrinsic mechanism, possibly involving prediagnostic immune alterations or defects in a cell cycle and apoptosis, which are more characteristic of indolent rather than aggressive lymphomas. Recent findings demonstrate substantial heterogeneity in the occurrence of a second malignancy by a lymphoma subtype, which suggests differences in etiology. Specifically, significantly different patterns of second malignancy after CLL/SLL, diffuse large B-cell lymphoma (DLBCL), and FL among patients without HIV/AIDS-related lymphoma have been reported. 5 Most notable were the elevated risks for lung cancer and melanoma after the more indolent lymphomas, but not after the more aggressive DLBCL. Furthermore, survivors of CLL/SLL and FL have demonstrated a greater risk of developing other nonhematologic malignancies (ie, salivary gland, colon, anus, and thyroid), whereas, in contrast, no evidence has been reported, to our