Abstract
Second primary malignancy is a serious late complication following anti-cancer treatments including chemotherapies, immune therapies, and radiotherapies. Prolonged use of rituximab-containing immunochemotherapies in patients with non-Hodgkin lymphoma can impair immune surveillance, potentially increasing the risk of severe infections and second primary malignancies. Here, we report the case of a patient initially diagnosed with follicular lymphoma, who then developed mantle cell lymphoma 11 years later. After several rounds of rituximab-containing therapies, the patient had impaired immunity and experienced severe SARS-CoV-2 pneumonia and hyperleukocytosis, which induced the hyperinflammatory responses, resulting in hemophagocytic lymphohistiocytosis (HLH). Early intervention halted the progression of HLH; however, leukocytosis and thrombocytosis recurred, eventually leading to the diagnosis of a third hematologic malignancy - chronic myeloid leukemia. Treatment with flumatinib improved the patient's condition. This case underscores the importance of monitoring immune depression and subsequent malignancies as more patients achieve long-term survival with hematologic cancers due to evolving therapeutic advances. Early recognition and adequate supportive therapies are crucial, especially in managing elderly patients with malignancies.