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.