Suggested CLL management algorithm. Assessment [disease biology, patient fitness (age), and treatment history] is indicated in white boxes, and corresponding treatment is in orange boxes. (A) Initial treatment of patients with CLL requires determination of iwCLL criteria for “active disease.” These patients should then be clinically evaluated for fitness and require FISH analysis for 17p13 deletion (17p−) and mutation analysis of TP53. (B) In patients with relapsed/refractory CLL, the response to previous treatment should also be considered; in case of response duration of 2 to 3 years or longer (late relapse), retreatment with a chemoimmunotherapy regimen should be considered. In contrast, patients with response duration of <2 to 3 years should be considered to be treated with nonchemotherapy regimens. FISH analysis for 17p13 deletion (17p−) and mutation analysis of TP53 should be repeated before treatment initiation. Alem indicates alemtuzumab; B, bendamustine; BSC, best supportive care; CR, complete response; Ibr, ibrutinib; Idela, idelalisib; Obi, obinutuzumab; Ofa ofatumumab; PD progressive disease; PR, partial response; SD, stable disease; w & w, watch and wait. Alemtuzumab is no longer licensed for CLL and should be considered only in exceptional cases when other treatments are not an option. Treatment options in frail (very old) patients need highly individualized decisions. (Modified based on the Onkopedia Guidelines of the German Society of Hematology and Oncology, available at www.onkopedia-guidelines.info.)