Monoclonal B-cell lymphocytosis in the bone marrow: revisiting the criteria for chronic lymphocytic leukemia/small lymphocytic lymphoma

Monoclonal B-cell lymphocytosis is a clonal B-cell population in the peripheral blood (PB) of < 5x10(boolean AND)9/L without extramedullary (EM) disease, often with a chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) phenotype. The degree of bone marrow (BM) involvement is not currently a part of the diagnostic criteria for MBL or CLL/SLL, but CLL-type MBLs in BM can be seen in patients lacking PB lymphocytosis. Data are limited on the outcome of such cases. We assessed the clinicopathologic characteristics of isolated BM CLL-type MBL in patients who did not meet criteria for CLL/SLL. We evaluated BMs from 2006 to 2018 with CLL-like clonal B-cell populations in patients with a PB absolute lymphocyte count or monoclonal B-cell count of <5 x 109/L and without definite evidence of EM disease. We investigated the extent and pattern of marrow involvement, PB counts, flow cytometric data, genetics, concurrent hematopoietic diseases, and outcomes including progression and treatment. Thirty cases with BM MBL but <5x10E9/L PB monoclonal B cells and no EM disease were identified. Thirteen of 30 had additional hematopoietic neoplasms. The mean patient age was 74.1 years (median: 77 years, range: 43 -91 years). No patients had lymphadenopathy (LAD) or splenomegaly by physical examination. By imaging, nine of 18 had LAD (8/9 < 1.5 cm) and four of 18 had splenomegaly but with other attributable etiologies. Mean PB absolute lymphocyte count (ALC) was 1.8x10E9/L (range: 0.5-5.0x10E9/L). Twenty-four of 30 (80%) had low-level (<20%) BM involvement by MBL, and among these, none with available follow-up data progressed to diagnostic CLL/SLL. Six of 30 (20%) had >20% marrow involvement by MBL. Four of 6 were treated for CLL/SLL due to cytopenias, despite not meeting diagnostic criteria, and all 4 were CD38 or ZAP70 positive and had cytogenetic abnormalities, including trisomy 12. One of 6 developed overt CLL/SLL 3 years later and had cytogenetic abnormalities at the time of