Evaluation and Management of Disease Transformation in Waldenström Macroglobulinemia

KEY POINTS Histologic transformation should be suspected in patients with WM that develop constitutional symptoms, rapidly progressive lymphadenopathy, extranodal involvement, sudden rise in LDH levels, and/or decreased serum IgM levels. Tissue biopsy is mandatory to diagnose histologic transformation and may be directed by clinical or radiologic features (ie, by site of rapidly enlarging lymph nodes, or by site of increased avidity on 18FFDG-PET/CT). Histologic diagnosis is required to confirm transformation to high-grade lymphoma. Most transformation events are caused by DLBCL variants, but rarely other aggressive lym phomas may occur. Treatment with intermediate-dose chemoimmunotherapy, such as R-CHOP, is the preferred option. CNS prophylaxis with HD-MTX should be considered if feasible and consolidation with autologous SCT should be discussed in fit patients responding to chemoimmunotherapy. If available, enrollment in clinical trials should be recommended.