PS994 OLIGOMONOCYTIC CHRONIC MYELOMONOCYTIC LEUKEMIA (O‐CMML) SHARES IMMUNOPHENOTYPIC AND MOLECULAR CHARACTERISTICS WITH CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)
Authors: Calvo X. , Párraga I. , Ferrer A. , Montesdeoca S. , Valls J. , Gisbert N. García , Fernández‐Rodríguez C. , Costan B. , Navarro R. , Pedro C. , Angona A. , Puiggrós A. , Salido M. , Espinet B. , Bellosillo B. , Florensa L. , Arenillas L. 
Published: June 2019

Background:

Diagnosis of CMML according to WHO 2017 requires the presence of ≥1x109/L and ≥10% of monocytes in peripheral blood (PB). Recently, Geyer et al. described oligomonocytic CMML (O‐CMML) as those MDS cases with relative monocytosis (≥10% monocytes) and monocyte count 0.5<1x109/L. The authors showed that molecular signature and outcome of OCMML were similar to overt CMML, suggesting that this represents an earlyphase of CMML. The study of peripheral monocyte subsets by flow cytometry (FC) has gained interest for CMML diagnosis. As showed by SelimogluBuet et al., the increase in the fraction of classical monocytes (Mo1) to >94% of total monocytes is a highly sensitive and specific diagnostic marker for CMML

Aims:

Since O‐CMML seems to be in the continuum of CMML, it is crucial to determine if these patients show a PB monocyte subset distribution similar to CMML. CD56 expression in monocytes is a typical feature of CMML and is rarely observed in MDS, therefore it seems interesting to assess this feature in O‐CMML. Finally, we evaluate if O‐CMML showed a high incidence of TET2/SRSF2 co‐mutation, the gene signature of CMML

Methods:

42 CMML, 20 O‐CMML, 8 MDS without relative monocytosis and 70 reactive monocytosis with ≥1x109/L monocytes (N = 140) were prospectively studied from 02/2016 to 02/2019. Patient characteristics are summarized in Table 1. We performed FC study of monocyte subsets in PB describing Mo1 (CD14bright/CD16‐), Mo2 (CD14bright/CD16+) and Mo3 (CD14dim or ‐/CD16bright). In addition, we assessed the expression of CD56 in monocyte population (cutoff positivity ≥ 20%). Finally, we applied a custom NGS gene panel focusing on TET2/SRSF2 co‐mutation (VAF detection sensitivity: 0.02). Comparisons were evaluated by Chi‐Square test, Fisher exact test or Man‐Whitney U‐test as appropriate

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Results:

a)The median percentage of classical monocytes (Mo1) was significantly inferior when comparing O‐CMML with CMML (96% vs 98%; P = 0.009) but O‐CMML showed a significant higher median percentage than MDS (88%; P = 0.001) and reactive monocytosis (89.9%; P < 0.001). No significant differences were observed between MDS and reactive monocytosis group (P = 0.296).

b)The percentage of patients with >94% Mo1 was no significantly different when comparing O‐CMML and CMML (74% vs 86%; P = 0.294), nevertheless the percentage of O‐CMML patients showing this feature was significantly higher in comparison with MDS (0%; P = 0.001), the group where these patients are currently included following WHO 2017 criteria, and reactive monocytosis (20%; P < 0.001). Table 2.

c) No differences were observed in the percentage of patients showing CD56 expression in monocytes when comparing O‐CMML and CMML (68.4% vs 69%; P = 0.92), nevertheless MDS (12.5%; P = 0.001) and reactive monocytosis (8.6%; P < 0.001) showed this feature in very few cases. Table 2.

d)We observed no significant difference in the presence of TET2/SRSF2 co‐mutation between O‐CMML and CMML (42% vs 35%; P = 0.73). This was not detected in MDS.

e)The sensitivity (S) and specificity (SP) of the Mo1>94% test was lower in our series than the originally reported by the GFM group (S: 90%; SP: 95%). Our S and SP was 86% and 71% with a PPV of 56% and a NPV of 92%. This could be explained by a high number of false positives since O‐CMML patients are currently considered as MDS. When considering these as CMML the test performed better with a S and SP of 82% and a PPV and NPV of 78% and 85% respectively.

Summary/Conclusion:

Our data support the diagnosis of O‐CMML as a distinctive entity with biological features similar to CMML