PB1962 THE HIGH INCIDENCE OF MICROCYTOSIS IN THE CONTEXT OF MONOCLONAL PERIPHERAL BLOOD LYMPHOCYTOSIS IN THE LEUKEMIC PHASE OF LYMPHOPROLIFERATIVE DISORDERS
Authors: Pereira M. , Marques G. , Ribeiro L. , Paiva A. , Rodrigues F. 
Published: June 2019

Background:Microcytosis is an established finding in chronic or inflammatory disease. Within this context, it is often described in lymphoid lineage hematologic malignancies, especially Hodgkin's lymphoma. Chronicity or a pro‐inflammatory state, however, are not the only predictors of a microcytic hemogram, with some chronic lymphoproliferative disorders (LPD) ‐ such as chronic lymphocytic leukemia (CLL) – rarely presenting with microcytosis, while the leukemic phase of other LPDs often presents with microcytosis.Aims:To clarify the relationship between monoclonal lymphocytosis in LPD and microcytosis.Methods:We analyzed all samples from adult patients (pts) with lymphocytosis (absolute lymphocyte count (ALC) >4.0 G/L), with analysis of clonality by flow cytometry, over a 4‐year period. A Control group of 50 pts with a LPD but without lymphocytosis and without clonality was selected.Results:We obtained 412 samples (51.4% male); 22.6% of patients had no hematological disease and a reactive polyclonal lymphocytosis (“Reactive”); 8.5% had a known hematologic disease, but polyclonal reactive lymphocytes (“Polyclonal”); and 68.9% had a pathologic monoclonal lymphocytosis (“Monoclonal”). Monoclonal pts had a CLL‐like phenotype in 69.7% of cases, marginal zone (MZL) in 14.8%, and large granular lymphocyte leukemia in 3.2%; follicular (FL), mantle cell (MCL), lymphoplasmacytic (WM), Sézary's, NK cell, and T‐prolymphocytic leukemia phenotypes accounted for <3% of cases, each; the remainder were non‐Hodgkin's Lymphomas, NOS. ALC ranged from 4.0‐141.1 G/L, with a mean of 16.4 ± 23.6 and a median of 6.8. The mean Reactive ALC was 5.0 ± 1.4 G/L, 5.2 ± 1.5 for Polyclonal and 21.4 ± 26.9 for Monoclonal pts (p < 0.001), with 14.4 ± 19.4 for non‐CLL pts (p < 0.001). Controls had an ALC of 1.8 ± 0.9 G/L.MCV ranged from 64.3‐111.1 fL, with a mean of 90.6 ± 6.1 and a median of 90.9; the Control median was 90.2 (74.1‐104.7 fL) with a mean of 90.5 ± 6.4 (p = NS); 91.0% of samples were normo‐, 5.8% macro‐ and 3.2% microcytic (p = NS vs Control). The mean Reactive MCV was 88.7 ± 4.7, 88.8 ± 6.3 for Polyclonal and 91.5 ± 6.4 for Monoclonal pts (p < 0.001), with microcytosis in 1.1%, 5.7% and 3.5% of pts, respectively (p = 0.044). Within B Cell lineage Monoclonal pts, the mean MCV was 92.3 ± 5.5 fL in CLL (p = 0.04 vs Control), 89.1 ± 7.9 in the indolent lymphomas (MZL, FL, WM; p = NS vs Control) and 84.5 ± 9.2 in MCL (p = 0.02 vs Control) (p < 0.001), with microcytosis in 0.5%, 7.8% and 50% of pts, respectively (p < 0.001).A posteriori longitudinal analysis of the MCV in microcytic pts during and after chemotherapy documented a correlation between the decrease in lymphocytosis and an increase in MCV, with improvement/resolution of microcytosis.Summary/Conclusion:We observed that reactive polyclonal lymphocytosis in non‐hematologic patients and in malignant hematology pts associated with identical average MCVs, overlapping with the mean MCV of a control population without lymphocytosis. Similarly, monoclonal lymphocytosis in the context of the indolent B cell lymphomas (MZL, FL and WM) did not significantly affect normocytosis. On the other hand, CLL tended to associate with significantly higher MCVs than controls or reactive polyclonal lymphocytoses.In contrast, a monoclonal lymphocytosis in the context of a leukemic phase of MCL associated significantly with a microcytic phenotype ‐ remarkably, we found that microcytosis was 100x more frequent in MCL (50% of cases) than CLL (0.5%).The effective treatment of the underlying LPD, and the resolution of clonal lymphocytosis, associated with a normalization of the MCV.