Chronic lymphocytic leukemia with proliferation centers in bone marrow is associated with younger age at initial presentation, complex karyotype and TP53 disruption

Summary The presence of expanded proliferation centers (PCs) in lymph nodes involved by chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma has been associated with adverse clinical outcomes, but the frequency and significance of PCs in bone marrow (BM) remain unclear. The study group included 36 patients with BM involvement by CLL in which PCs were present. We compared this group with 110 randomly selected BM samples involved by CLL without morphologically discernable PCs. Patients with PCs in BM were younger (median age, 53 years [range,18-71 years] versus 58 years [range, 31-82 years]; P =  .007), more frequently experienced B symptoms (27.8% versus 8.2%, P =  .0076 ), more often had Rai stage IV disease (30.6% versus 17.3%, P =  .02) and higher serum lactate dehydrogenase ( P =  .0037) and β 2 -microglobulin ( P =  .0001) levels, and lower hemoglobin ( P =  .026) and platelet counts ( P =  .0422). TP53 alterations were more common in patients with PCs in BM (45.4% versus 18.7%; P =  .0049), as was a complex karyotype (26.4% versus 9%; P =  .019). There were no significant differences in the frequency of ZAP70 or CD38 positivity or IGHV mutation status. The median time to first treatment was shorter in patients with PCs in BM (7 months versus 19 months, P =  .047), and the frequency of Richter syndrome was higher (14% versus 4%, P =  .041). Patients with PCs in BM had significantly shorter overall survival compared with the control group (median, 249.3 months versus undefined; P =  .0241). These data suggest that identification of PCs in BM samples involved by CLL is associated with adverse prognostic features.