Monocytosis at the time of diagnosis has a negative prognostic impact in myelodysplastic syndromes with less than 5% bone marrow blasts

Abstract

The prognostic impact of monocytosis has not yet been determined in patients with myelodysplastic syndromes (MDS). We examined absolute monocyte counts in the peripheral blood at the time of diagnosis in 1949 patients with a bone marrow blast count < 5%, a condition we call MDS < EB1 (MDS with a blast percentage lower than that of MDS with excess blasts 1, according to the WHO classification). Monocytosis (> 600/µl) was associated with higher median hemoglobin, WBC, and ANC, and more favorable karyotype (p = .001). Nevertheless, monocytosis was associated with shorter overall survival (OS) (108 vs. 126 months, p = .002) and earlier transformation into AML (p < .001). In patients with sideroblastic phenotype, the percentage of ring sideroblasts significantly correlated with the monocyte count (p = .005), and OS was significantly shorter when monocytosis was documented (88 vs. 132 months, p = .004). The survival disadvantage of patients with MDS < EB1 and peripheral blood monocytosis suggests that these patients suffer from a CMML-like disease. Even though they are generally classified as MDS with persistent monocytosis, such patients should be considered candidates for therapeutic options employed in CMML.

Chronic myelomonocytic leukemia with ring sideroblasts/SF3B1 mutation presents with low monocyte count and resembles myelodysplastic syndromes with-RS/SF3B1 mutation in terms of phenotype and prognosis

“…and Silzle et al., which, in a population of MDS with low blast count, have recently shown that monocytosis >0.6 x10 9 /L is associated with a shorter OS, also in the subtype enriched with RS. This suggests that MDS with monocytosis and CMML with RS may be located in a “gray zone” that makes diagnosis challenging but, on the other hand, supports a therapeutically similar approach in these cases ( 14 , 15 ). Altogether, this study supports the notion that classifications based on selected clinical characteristics, generally with arbitrarily chosen thresholds, have always inherent limitations.…”

“…On the other hand, monocytosis (monocyte count >0.6 x10 9 ) is not uncommon in patients with MDS with low blast count (< 5%). Within the RS phenotype, 20% of patients show monocytosis and there seems to be a positive correlation between the percentage of RS and absolute monocyte count, with the overall survival (OS) being significantly shorter ( 14 ). Moreover, the absolute monocyte count at diagnosis may affect the prognosis in MDS independently of the Revised International Prognostic Score System (IPSS-R) risk score, and monocytopenia (<0.2 x10 9 /L) may be associated with a higher risk of acute myeloid leukemia (AML) transformation ( 15 ).…”

<i>TET2</i> mutational status affects myelodysplastic syndrome evolution to chronic myelomonocytic leukemia

“…Sihem Tarfi, 1,2 Quentin Barathon, 2 Bouchra Badaoui, 2 Nicolas Freynet, 2 Vincent Parinet, 1,5 Mathieu Leclerc, 1,5 Sébastien Maury,…”

“… 9 The mean number of mutations per sample in CMML-like MDS patients (3.5±0.2) was the same as that of CMML patients (3.5±0.3) and significantly higher than that of other MDS patients (1.7±0.3; P ≤0.0001, unpaired t test with Welch’s correction). In the learning cohort, TET2 was the most frequently mutated gene in the three groups of patients, with a similar proportion of patients carrying at least one TET2 mutation in CMML (68.2%) and CMML-like MDS (66.7%) ( P =0.92, Χ 2 test) while this proportion was lower in other MDS (34.6%; P =0.036, Χ 2 test) ( Figure 1E ).…”

“…Nevertheless, several reports suggested that up to 30% of myelodysplastic syndrome (MDS) evolved into genuine CMML, 1 raising for many years the question of a “preCMML” state. 2 An oligo-monocytic CMML entity was subsequently described in patients displaying a relative monocytosis with an absolute monocyte count between 0.5x10 9 /L and 1x10 9 /L, 3 , 4 providing a rationale to revise CMML diagnosis criteria in the recent 5 th edition of the WHO classification that considers a relative monocytosis ≥10% of WBC and an absolute monocyte count ≥0.5x10 9 /L. 5 An increased fraction of circulating classical monocytes (cMO, defined by flow cytometry as CD14 ++ CD16 - fraction) ≥94%, which was shown to distinguish CMML from reactive monocytosis, 1 , 6 was included as a supportive criterion for CMML diagnosis.…”