For patients with WM and IgM levels > 4000 mg/dL, prophylactic TPE should be performed prior to receiving rituximab, even in the absence of HVS symptoms, as rituximab can cause a transient IgM increase or “IgM flare” related to its rapid release from the necrotic cancer cells causing emergence or deterioration of existing symptoms [40]. This evidence concerns the gene CD40LG and cancer.