Persistence of Residual Normal Peripheral Blood B Cells in Newly Diagnosed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Identifies a Good Prognostic Subgroup
Pedro Horna, Steven H Kroft, Alexandra M Harrington, Horatiu Olteanu. Medical College of Wisconsin, Milwaukee
Background: Known prognostic indicators for CLL/SLL are clinical stage, cytogenetic / molecular findings, and CD38 expression on tumor cells. Peripheral blood (PB) flow cytometry (FC) is part of the initial workup of patients (pts) with CLL/SLL, and can identify, quantify, and discriminate the neoplastic B-cell clone from normal residual B cells. No study has assessed the prognostic significance of normal B cells in PBs from CLL/SLL pts. We determined the proportion of normal B cells in a cohort of CLL/SLL pts and correlated it with clinical and pathologic parameters.
Design: 45 diagnostic PBs from pts with CLL/SLL, diagnosed according to 2008 WHO criteria, were evaluated by 4-color FC with antibodies against CD3, CD4, CD5, CD10, CD11c, CD19, CD20, CD22, CD23, CD38, CD45, FMC-7, and surface light chains. Normal and abnormal populations were identified by cluster analysis, and normal residual B cells were recorded as % of total lymphocytes. Clinical and laboratory data were available from chart review. Progression-free survival (PFS) was calculated from the time of diagnosis to initiation of treatment.
Results: Clinicopathologic findings for the 45 CLL/SLL pts are summarized in Table 1. Median follow-up was 1134 days (range, 290-2149), and 16/45 (35.6%) pts required treatment, at a median interval of 518 days from diagnosis. The median PFS was shorter in CLL/SLL pts that had a normal B cell % < 25th percentile, as compared to those with a normal B cell % > 25th percentile: 599 vs. 1310 days (p=0.008). In uni- and multivariate analysis, both the normal B cell % < 25th percentile (p<0.02) and CD38 expression on CLL/SLL cells (p<0.03) were identified as negative prognostic indicators for PFS.
Conclusions: 87% of CLL/SLLs have detectable normal residual B cells by FC. Cases with low (< 25th percentile) normal B cells have a shorter PFS, and this parameter is a significant poor prognostic indicator in multivariate analysis, independent of the absolute CLL/SLL count.
|Age; median (range)||69 (45-95)|
|Rai Stage 0||53.4%|
|Cases with detectable normal residual B cells||86.7%|
|WBC, cells/uL; median (range)||28,800 (13,200-187,300)|
|Absolute CLL/SLL count, cells/uL; median (range)||16,900 (6,400-168,600)|
|Hemoglobin, g/dL; median (range)||13.6 (6.6-15.5)|
|Platelets, x10e3/uL; median (range)||216 (9-414)|
|% normal residual B cells (of total lymphocytes)||0.14 (0.0-1.5)|
|Absolute normal residual B cell count; cells/uL||4.0 (0-49)|