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Maurer, C.; Langerbeins, P.; Bahlo, J.; Cramer, P.; Fink, A. M.; Pflug, N.; Engelke, A.; Tresckow, J. von; Kovacs, G.; Stilgenbauer, S.; Wendtner, C.-M.; Müller, L.; Ritgen, M.; Seiler, T.; Fischer, K.; Hallek, M.; Eichhorst, B. (2016): Effect of first-line treatment on second primary malignancies and Richter's transformation in patients with CLL. In: Leukemia, Vol. 30, No. 10: pp. 2019-2025
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This study aimed to assess the frequency of and the contributing factors for second primary malignancies (SPMs) and Richter's transformations (RTs) following first-line treatment of chronic lymphocytic leukemia within four phase II/III trials of the GCLLSG evaluating fludarabine (F) vs F+cyclophosphamide (FC), chlorambucil vs F, FC without or with rituximab, and bendamustine+R (BR). Among 1458 patients, 239 (16.4%) experienced either an SPM (N = 191) or a RT (N = 75). Solid tumors (N = 115;43.2% of all second neoplasias) appeared most frequently, followed by RTs (N = 75;28.2%). Patients showed a 1.23-fold increased risk of solid tumors in comparison to the age-matched general population from the German cancer registry. Age>65 (hazard ratio (HR) 2.1;P<0.001), male sex (HR 1.7;P = 0.01), co-morbidities (HR 1.6;P = 0.01) and number of subsequent treatments >= 1 (HR 12.1;P<0.001) showed an independent adverse prognostic impact on SPM-free survival. Serum thymidine kinase > 10 U/l at trial enrollment (HR 3.9;P = 0.02), non-response to first-line treatment (HR 3.6;P<0.001) and number of subsequent treatments >= 1 (HR 30.2;P<0.001) were independently associated with increased risk for RT.