Chronic lymphocytic leukemia with proliferation centers in bone marrow is associated with younger age at initial presentation, complex karyotype, and TP53 disruption.
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 β2-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.
['Garces|Sofia|S|', 'Khoury|Joseph D|JD|', 'Kanagal-Shamanna|Rashmi|R|', 'Salem|Alireza|A|', 'Wang|Sa A|SA|', 'Ok|Chi Young|CY|', 'Hu|Shimin|S|', 'Patel|Keyur P|KP|', 'Routbort|Mark J|MJ|', 'Luthra|Rajyalakshmi|R|', 'Tang|Guilin|G|', 'Schlette|Ellen J|EJ|', 'Bueso-Ramos|Carlos E|CE|', 'Medeiros|L Jeffrey|LJ|', 'Loghavi|Sanam|S|']
D059786:Abnormal Karyotype D000293:Adolescent D000328:Adult D000367:Age Factors D000368:Aged D000369:Aged, 80 and over D014408:Biomarkers, Tumor D001854:Bone Marrow Cells D016022:Case-Control Studies D049109:Cell Proliferation D005260:Female D020022:Genetic Predisposition to Disease D006801:Humans D015451:Leukemia, Lymphocytic, Chronic, B-Cell D008297:Male D008875:Middle Aged D010641:Phenotype D011379:Prognosis D018570:Risk Assessment D012307:Risk Factors D013997:Time Factors D016159:Tumor Suppressor Protein p53 D055815:Young Adult
Proliferation centers Bone marrow Complex karyotype TP53 Chronic lymphocytic leukemia/small lymphocytic lymphoma