Abstract
Current prognostic models for myelodysplastic syndromes (MDS), including the Revised International Prognostic Scoring System (IPSS-R), do not account for host immunity. We retrospectively examined the prognostic relevance of monocytopenia, lymphocytopenia and lymphocyte-to-monocyte ratio (LMR) in a cohort of 889 patients with primary MDS. After a median follow-up of 27 months, 712 (80%) deaths and 116 (13%) leukemic transformation were documented. In univariate analysis, subnormal absolute lymphocyte count (ALC) <0.9 × 109/l; P=0.001), ALC<1.2 × 109/l (P=0.0002), subnormal absolute monocyte count (AMC) <0.3 × 109/l (P=0.0003), LMR (P⩽0.0001) and LMR⩾5 (P=0.03) were all associated with inferior overall survival. In multivariable analysis that included other risk factors, significance was retained for LMR (P=0.02) and became borderline for ALC <1.2 × 109/l (P=0.06). Analysis in the context of IPSS-R resulted in P-values of 0.06 for ALC<1.2 × 109/l, 0.7 for monocytopenia and 0.2 for LMR. Leukemia-free survival was not affected by ALC, AMC or LMR. The observations from the current study suggest a possible detrimental role for altered host immunity in primary MDS, which might partly explain the therapeutic benefit of immune-directed therapy, including the use of immune modulators; however, IPSS-R-independent prognostic value for either ALC or AMC was limited.
Highlights
Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal hematopoietic stem cell disorders with an inherent tendency for leukemic transformation.[1]
It is possible that these surrogates of host immunity may partly account for disease progression and poor survival; the current study examines the possibility by studying the prognostic significance of absolute lymphocyte count (ALC), absolute monocyte count (AMC) and lymphocyte-to-monocyte ratio (LMR) at the time of diagnosis in primary MDS, in terms of both overall and leukemia-free survival
Transfusion need was documented in 33% of ALC, treated as either a continuous variable (P = 0.01) or a categorical variable with ALC cutoff values of o 0.9 × 109/l (P = 0.001; hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.1–1.5) or o1.2 × 109/l (P = 0.0002; HR 1.3, 95% CI 1.2–1.6; Table 2)
Summary
Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal hematopoietic stem cell disorders with an inherent tendency for leukemic transformation.[1]. In order to have accurate risk stratification of patients with primary MDS, formal prognostic models have been developed over the years. The International Prognostic Scoring System (IPSS) was introduced in 1997 followed by the World Health Organization Prognostic Scoring System in 2007, the global MD Anderson score in 2008 and the most recent Revised International Prognostic Scoring System (IPSS-R) in 2012. These prognostic models for MDS consider the number and severity of cytopenias, including anemia, thrombocytopenia and neutropenia, need for red blood cell transfusions, karyotype, bone marrow and peripheral blood blast percentage, leukocytosis, morphological subtypes, age and performance status.[3,4,5,6]
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