Prognostic Relevance of Monocytopenia and Lymphocyte-to-Monocyte Ratio in Primary Myelodysplastic Syndromes
Authors: Saeed Lyla , Patnaik Mrinal M , Begna Kebede H. , Al-Kali Aref , Litzow Mark R , Hanson Curtis A. , Ketterling Rhett P. , Pardanani Animesh , Gangat Naseema , Tefferi Ayalew 
Published: October 2019

Abstract

Background
We have previously shown an independent adverse prognostic effect of lymphopenia (absolute lymphocyte count <1.2 x 10(9)/L) for survival in MDS (Jacobs et al. Am J Hematol 2010;85:160) whereas others have suggested a similar value from lymphocyte-to-monocyte ratio (LMR); patients with LMR ≥5 experienced shorter survival with median 67 vs. 126 months (Mushtaq et al. JCO May 20 Supp. 2016:7062). Whether or not "monocytopenia" also carries a prognostic value in MDS is currently unknown and was the main objective for the current study, which also addresses the prognostic value of LMR.
Methods
We retrospectively recruited 889 consecutive patients with primary MDS who were untreated at the time of referral to our institution and in whom absolute monocyte count (AMC) and absolute lymphocyte count (ALC) at time of referral were documented. The diagnosis of MDS and leukemic transformation (LT) was made according to WHO criteria (Blood. 2009;114:937). Complete follow-up information was updated in January 2015. For the purposes of the current study, monocytopenia was defined as AMC below the lower limit of the institutional normal range, which was 0.3 to 0.9 x 10(9)/L. Comparisons of survival and other clinical parameters were performed between i) patients with and without monocytopenia and ii) patients with and without LMR ≥5. Conventional methods were used for statistical analysis.
Results
Patient characteristics:
Median (range) values for the 889 study patients (69% males) included: age 72 (18-98), hemoglobin 9.6 g/dL (5.4-15.7), leukocyte count 3.4 x 10(9)/L (0.4-35), platelet count 106 x 10(9)/L (2-1804), circulating blasts 0% (0-18), bone marrow blasts 3% (0-19) and absolute lymphocyte count (ALC) 1.2 x 10(9)/L (.02-8.9). Transfusion need was documented in 33% of patients and abnormal cytogenetics in 49%. Risk stratification by the revised international prognostic scoring system (IPSS-R) was very high in 11%, high in 16%, intermediate in 21%, low in 36% and very low in 16%. The median (range) AMC for the entire study population of 889 patients was 0.22 x 10(9)/L (0.0-1.8).The number of patients with subnormal AMC was 539 (61%). After a median follow-up of 27 months, 712 (80%) deaths and 116 (13%) leukemic transformations were documented.
Comparison of patients stratified by absolute monocyte count and LMR
Compared to patients with AMC >0.3 x 10(9)/L, MDS patients with monocytopenia displayed younger age (p<0.0001), lower hemoglobin (p=0.005), higher red blood cell transfusion need (p=0.03), lower leukocyte count (p<0.0001), lower platelet count (p<0.0001), lower absolute neutrophil count (p<0.0001), higher circulating (p=0.03) and bone marrow (p<0.0001) blasts, higher incidence of abnormal karyotype (p=0.03), and higher risk distribution in terms of both IPSS-R (p<0.0001) and cytogenetic risk stratification by IPSS-R (p=0.03).
In univariate analysis, lower AMC was associated with inferior survival (p=0.002); significance was even more apparent when comparing patients with and without monocytopenia (p=0.0003; HR 1.3, 95% CI 1.1-1.5). Similarly, there was significant association between LMR and survival (p<0.0001) with patients with LMR ≥5 experiencing inferior survival (p=0.03; HR 1.2; 95% CI 1.02-1.4). In multivariable analysis, the adverse effect of monocytopenia was shown to be independent of age (p<0.0001), gender (p=0.0001), anemia (Hemoglobin <10 g/dL; p=0.002), thrombocytopenia (platelets <100 x 10(9)/L; p=0.01), neutropenia (absolute neutrophil count <0.8 x 10 (9)/L; p=0.005), subnormal ALC (p=0.0008), circulating blast percentage (p=0.002), cytogenetic risk stratification by IPSS-R (p=0.006) and LMR (p=0.02) or LMR ≥5 (p=0.002); however, significance was lost when risk stratification by IPSS-R was added to the multivariable analysis (p=0.7). In regards to LMR, it retained its significance (p=0.009) during multivariable analysis that included monocytopenia or subnormal ALC, as covariates; however, significance was lost in the context of IPSS-R (p=0.24 for LMR and 0.8 for LMR ≥5)
Conclusions
Monocytopenia in MDS clusters with adverse disease features and both monocytopenia and higher LMR were associated with poor survival. Despite the display of prognostic independence from each other and other risk factors considered individually, the survival impact of neither monocytopenia nor LMR was found to be independent of IPSS-R.

Disclosures
Al-Kali: Novartis: Research Funding; Celgene: Research Funding.