Emerging utility of flow cytometry in the diagnosis of chronic myelomonocytic leukemia

Hudson, Chad A.; Burack, W. Richard; Bennett, John M.

doi:10.1016/j.leukres.2018.08.015

Cited by 18 publications

(18 citation statements)

References 26 publications

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“…This analysis demonstrates a low variability of cMo percentage quantification and validates the previously proposed 94% cutoff value, defining a robust, sensitive, and specific assay. Compared with genetic analyses, the simplicity of this flow cytometry approach may be likely increasingly widespread 31 , pending the demonstration of its clinical benefit that requires a prospective, international multicenter study.…”

Section: Discussionmentioning

confidence: 99%

Multicenter validation of the flow measurement of classical monocyte fraction for chronic myelomonocytic leukemia diagnosis

Tarfi

Harrivel

Dumézy

et al. 2018

Blood Cancer Journal

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Peripheral blood monocytes include three subsets defined by CD14 and CD16 surface markers. An increase in the CD14++CD16− classical monocyte fraction ≥ 94% of the total monocytes was proposed to rapidly and efficiently distinguish chronic myelomonocytic leukemia from reactive monocytosis. The robustness of this assay required a multicenter validation. The flow cytometry assay designed to quantify peripheral blood monocyte subsets was implemented by multiple diagnosis laboratories in France. A nationwide survey was performed to evaluate its performance. All the 48 French laboratories answered the questionnaire, revealing that 63% use this assay routinely. Central blind reanalysis of 329 cytometry files collected from five laboratories demonstrated an excellent correlation in classical monocyte fraction measurement (r = 0.93; p < 0.0001). The cutoff value of 94% classical monocytes being the critical readout for diagnosis, we then compared 115 patients with classical monocytes ≥ 94% and 214 patients with a fraction < 94% between initial analysis and reanalysis. An agreement was obtained in 311 files. Finally, an overt diagnosis, available for 86 files, confirmed a good sensitivity (93.6%) and specificity (89.7%). This survey demonstrates the robustness of the flow assay with limited variability of classical monocyte percentage between centers, validates the 94% cutoff value, and confirms its sensitivity and specificity.

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Section: Discussionmentioning

confidence: 99%

Multicenter validation of the flow measurement of classical monocyte fraction for chronic myelomonocytic leukemia diagnosis

Tarfi

Harrivel

Dumézy

et al. 2018

Blood Cancer Journal

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“…Recently, emphasis has been given to the distribution of monocyte subsets (classical, intermediate and non-classical) in peripheral blood based on their expression of CD14 and CD16 16 , 17 , for the diagnosis of chronic myelomonocytic leukemia (CMML) and its differential diagnosis with MDS presenting peripheral relative but not absolute monocytosis. Several studies have shown that in CMML, the proportion of classical (CD16 - ) monocytes are increased in CMML compared to cases of reactive monocytosis.…”

Section: Discussionmentioning

confidence: 99%

“…In granulocytic precursors we assessed hypogranularity (SSC of granulocytes/SSC lymphocytes ratio, according to Ogata 6 ) and decrease or increase (1 standard deviation from normal) in expression of CD11b, CD13 and CD16. Besides, the percentages of all monocytes, those of classical (CD14 + /CD16 − ) and of CD16 + monocytes among total nucleated cells and their proportion among all monocytes 17 , as well as decrease in expression of HLA-DR, CD11b, CD14 and CD64 were examined. Cross-lineage expressions of CD56 and CD7 in granulocytes and monocytes (20% of the cells) were also assessed 2 , 10 , 11 .…”

Section: Methods and Development Of The Scorementioning

confidence: 99%

“…Especially, we have addressed the distribution of the subsets of monocytic precursors in BM based on their expression of CD14 and CD16. The importance of these subsets in peripheral blood has been recently shown for the diagnosis of chronic myelomonocytic leukemia (CMML) 16 , 17 . However, their distribution in BM has not been studied in detail.…”

Section: Introductionmentioning

confidence: 99%

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A simple score derived from bone marrow immunophenotyping is important for prognostic evaluation in myelodysplastic syndromes

Vido-Marques

Reis-Alves

Saad

et al. 2020

Sci Rep

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Immunophenotyping of bone marrow (BM) precursors has been used as an ancillary diagnostic tool in myelodysplastic syndromes (MDS), but there is no general agreement about which variables are the most relevant for prognosis. We developed a parsimonious prognostic model based on BM cell populations well-defined by phenotype. We analyzed 95 consecutive patients with primary MDS diagnosed at our Institution between 2005 and 2012 where BM immunophenotyping had been performed at diagnosis. Median follow-up: 42 months (4–199). Median age: 67 years (33–79). According to IPSS-R, 71 cases were low or intermediate risk. Flow variables significant in the univariate Cox analysis: “%monocytes/TNCs”, “% CD16+ monocytes/TNCs”, “total alterations in monocytes”, “% myeloid CD34+ cells”, “number of abnormal expressions in myeloblasts” and “% of B-cell progenitors”. In the multivariate model remained independent: “% myeloid CD34+ cells”, B-cell progenitors” and “% CD16+ monocytes/TNCs”. These variables were categorized by the extreme quartile risk ratio strategy in order to build the score: % myeloid CD34+ cells” (≥ 2.0% = 1 point), B-cell progenitors” (< 0.05% 1 point) and “CD16+ monocytes/TNCs” (≥ 1.0% 1 point). This score could separate patients with a different survival. There was a weak correlation between the score and IPSS-R. Both had independent prognostic values and so, the flow score adds value for the prognostic evaluation in MDS.

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“…CMML is characterized by an increase in the fraction of classical monocytes ≥94% at the expense of intermediate and nonclassical monocytes, whereas nonclonal monocytosis is due to the accumulation of intermediate and nonclassical monocytes . This flow cytometry assay has a good sensitivity (93.6%) and specificity (89.7%) and can be implemented in multiple diagnostic laboratories with an excellent correlation in the classical monocyte fraction measurement . Monocytosis is a frequent abnormality on a complete blood count (CBC) and differential, and strictly following the WHO recommendations (ie, reviewing the blood smear for signs of myelodysplasia or excess blasts if the WHO criteria for CMML are met) would generate a microscopic blood smear review in around 6%‐7% of samples (6.5% in our experience).…”

Section: Introductionmentioning

confidence: 99%

A hierarchical approach in the diagnostic workflow of chronic myelomonocytic leukemia: Pivotal role of the “Mono‐dysplasia‐score” combined with flow cytometric quantification of monocyte subsets

Zhu

Sourdeau

Aubert

et al. 2019

Int J Lab Hematology

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Introduction:Monocytosis is a frequent trigger for blood smear review in a routine hematology laboratory whereas chronic myelomonocytic leukemia (CMML) is infrequent and arises mostly in elderly patients. In order to define the best workflow for monocytosis, we studied three diagnostic approaches: the classical morphology approach (blood smear review), the flow cytometry assay (quantification of monocyte subsets as described by Selimoglu-Buet et al in 2015), and the "mono-dysplasiascore" also referred to as "Monoscore (as described by our team in 2018 using the structural parameters of the Sysmex XN™ analyzers). Methods:Studying a multicentric cohort of 196 nonclonal monocytoses and CMML patients aged over 50 years, we compared the diagnostic performance of the three approaches alone and in combination to propose a diagnostic decision tree. Results:In patients presenting with additional criteria for slide review to monocytosis (37% of our cohort), we propose to sequentially combine morphology, Monoscore, and flow cytometry. On the contrary, for patients with isolated monocytosis (63%), slide review is not mandatory and we suggest performing flow cytometry depending on the Monoscore value. Using the proposed algorithm, 98% of CMML patients would have been correctly identified, slide review rate drastically reduced, and flow cytometry would have been carried out in 44% of patients. Conclusion:We have shown that implementation of Monoscore is a useful input filter to significantly reduce slide reviews without losing sensitivity and that flow cytometry is a performant technique in the second step of the diagnostic workup of CMML. K E Y W O R D S chronic myelomonocytic leukemia, classical monocytes fraction, flow cytometry, monocyte subsets, mono-dysplasia score | 783 ZHU et al.

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Emerging utility of flow cytometry in the diagnosis of chronic myelomonocytic leukemia

Cited by 18 publications

References 26 publications

Multicenter validation of the flow measurement of classical monocyte fraction for chronic myelomonocytic leukemia diagnosis

Multicenter validation of the flow measurement of classical monocyte fraction for chronic myelomonocytic leukemia diagnosis

A simple score derived from bone marrow immunophenotyping is important for prognostic evaluation in myelodysplastic syndromes

A hierarchical approach in the diagnostic workflow of chronic myelomonocytic leukemia: Pivotal role of the “Mono‐dysplasia‐score” combined with flow cytometric quantification of monocyte subsets

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