scholarly journals Analysis of erythroid maturation in the nonlysed bone marrow with help of radar plots facilitates detection of flow cytometric aberrations in myelodysplastic syndromes

2020 ◽  
Vol 98 (5) ◽  
pp. 399-411 ◽  
Author(s):  
Despoina Violidaki ◽  
Olof Axler ◽  
Katayoon Jafari ◽  
Filippa Bild ◽  
Lars Nilsson ◽  
...  
Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1661-1661
Author(s):  
Theresia M Westers ◽  
Canan Alhan ◽  
Claudia Cali ◽  
Gert J Ossenkoppele ◽  
Arjan A van de Loosdrecht

Abstract Flow cytometry (FCM) in myelodysplastic syndromes (MDS) is recognized as a useful tool in identifying aberrancies in expression of differentiation antigens on immature and mature bone marrow cells of erythroid and myelomonocytic lineages. FCM in MDS correlates significantly to morphology according to WHO and the WHO-based Prognostic Scoring System (WPSS). Moreover, certain aberrancies in pure RA+/−RS patients, i.e. CD7 on myeloid blasts, seemed to predict transfusion dependency and disease progression independent of classical prognostic parameters such as WHO, cytogenetics and IPSS (Van de Loosdrecht et al., Blood 2008, 111). Flow cytometric aberrancies in bone marrow of 29 patients with low or int-I risk MDS were analyzed at diagnosis and after approximately 1 year of treatment with a standardized regimen of Epo (NeoRecormon®) and G-CSF (median: 12 months (range: 4–24) in order to evaluate the value of FCM in disease monitoring. Patients were classified as RA+/−RS (n=11), RCMD+/−RS (n=15), 1 hypoplastic MDS, 1 MDS-U and 1 MDS/MPD. Progression was defined as an increase in WHO subgroup to at least RAEB-1 within 18 months after diagnosis of MDS. Before treatment, median number of aberrancies in the myelomonocytic lineage, as assessed by FCM, was 4 in RA+/−RS (range 1–8) and 5 in RCMD+/−RS (range 3–10); other MDS subgroups were too small. In age-matched normal bone marrow samples the median number of aberrancies was 1 (range 0–3, n=18). Aberrant expression of CD5, CD7 or CD56 was observed on myeloid blasts at diagnosis in 13 out of 18 patients that were transfusion-dependent or suffered from progressive disease during follow-up (4 RA+/−RS, 7 RCMD+/−RS, 1 MDS-U and 1MDS/MPD). Interestingly, expression of these markers was only detected in 1 out of 11 patients that were not or low transfusion dependent. This particular RCMD-RS patient had short response duration. The number of blast aberrancies correlated significantly to transfusion dependency and disease progression (r=0.459, p=0.012). Nine patients showed hematological improvement upon Epo/G-CSF treatment. In most of these patients (4/6 RA+/−RS and 2/3 RCMD+/−RS) the number of flow cytometric aberrancies decreased (median 4 at diagnosis to 2.5 at follow-up in all responders). This decrease was caused by a diminished number of monocytic aberrancies (p=0.028); a stable blast aberrancy was seen in only one patient. In 15 patients with stable disease, no significant changes in the number of flow cytometric aberrancies could be detected (median 5 and 5, at diagnosis and follow-up, respectively); whereas in 4 of the 5 patients with progressive disease during Epo/G-CSF (2/2 RA+/−RS, 1/2 RCMD+/−RS and 1 MDS/MPD) the number of aberrancies increased (median 7 and 9, at diagnosis and follow-up, respectively). This increase was mainly caused by changes in the number of aberrancies in blast and granulocyte subpopulations. The response to therapy seems to depend on the number of blast aberrancies (r=0.351, p=0.062). From these data we hypothesize that FCM can be used as an objective sensitive disease monitoring parameter in low/int-I risk MDS. Furthermore, in a subset of these patients treatment with Epo/G-CSF might have altered disease progression reflected by normalization or stabilization of aberrancies on myelomonocytic cells. This underscores observations that Epo/G-CSF improves overall survival and/or leukemia free survival. Prospective studies are being conducted to validate flow cytometric analysis in the diagnosis, prognostication and disease monitoring of low/int-I risk MDS during Epo/G-CSF and lenalidomide. To conclude, FCM can contribute to the management of low/int-I risk MDS patients as changes in the number of flow cytometric aberrancies reflect response to treatment.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3105-3105
Author(s):  
Konstantinos Dimopoulos ◽  
Olga Kristina Hansen ◽  
Jakob Werner Hansen ◽  
Lene Sjö ◽  
Leonie Saft ◽  
...  

Abstract Introduction and aims The term ICUS is used to describe cases with persistent cytopenia (more than 6 months) without evidence of dysplasia in the bone marrow (BM) smear, and normal cytogenetics. Flow cytometry is currently a standard tool for the diagnosis of myelodysplastic syndromes (1). Our goal was to evaluate the efficacy of flow cytometry in detecting bone marrow dysplasia in the absence of abnormal morphology. Materials and methods A total of 79 patients with ICUS and 12 patients with MDS were analyzed with a standardized flow cytometry panel (2). Data were analyzed using two different algorithms; the Ogata algorithm (3) and Wells algorithm (4). For each of the algorithms, samples were classified as suggestive for dysplasia when scoring equal to or higher than 2. Furthermore, all ICUS patients were screened for mutations using targeted sequencing of 20 genes (DNMT31, TET2, EZH2, SRSF2, CBL1, SF3B1, UAF1, GATA2, IDH1, IDH2, CEBPa1, ZRSR2, TP53, KRAS, NRAS, ETV6, RUNX1, JAK2 and ASXL1) and 57/71 samples were additionally evaluated for signs of dysplasia by two independent hematopathologists. Results The diagnostic value of flow cytometry in MDS was confirmed by our data; the Wells algorithm was slightly superior to Ogata algorithm in predicting MDS (10/12 patients (83.3%) vs. 7/12 patients (58.3%) respectively, fig. 1A) and was therefore the main algorithm used for the further analysis of the ICUS patients. Flow cytometry was suggestive of dysplasia in 34/79 (43%) patients with ICUS. Interestingly, in patients with at least one detected mutation, flow cytometry was positive in 23/42 (54.8%) of the cases, while it was positive in 8/9 (88.9%) patients with more than two mutations (fig. 1C). There was no higher frequency of abnormal flow cytometry in patients with higher risk mutations. Additionally, for the 57 patients evaluated for dysplastic changes, flow cytometric abnormalities were more frequent (p= 0.05) in the 22 patients with moderate/severe dysplasia (15/22 patients or 68.2%, fig. 1D). After a median follow-up of 20 months (range: 3 - 90), a total of eight patients progressed to either MDS, CMML or AML. Interestingly, these eight patients had flow cytometric abnormalities suggestive of dysplasia before developing hematological malignancy. In conclusion, flow cytometry can identify a subgroup of ICUs patients with a higher mutational burden, dysplastic changes and a higher risk for progression to MDS or a more aggressive myeloid disease and has a place in the diagnostic evaluation of patients with idiopathic cytopenia. References: Porwit A, Van De Loosdrecht AA, Bettelheim P, Eidenschink Brodersen L, Burbury K, Cremers E, et al. Revisiting guidelines for integration of flow cytometry results in the WHO classification of myelodysplastic syndromes - Proposal from the International/European LeukemiaNet Working Group for Flow Cytometry in MDS. Leukemia. 2014;28(9):1793-8. van Dongen JJM, Lhermitte L, Böttcher S, Almeida J, van der Velden VHJ, Flores-Montero J, et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia [Internet]. 2012 Sep [cited 2014 Nov 28];26(9):1908-75. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3437410&tool=pmcentrez&rendertype=abstract Porta MGD, Picone C, Pascutto C, Malcovati L, Tamura H, Handa H, et al. Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: Results of a European LeukemiaNET study. Haematologica. 2012;97(8):1209-17. Wells DA, Benesch M, Loken MR, Vallejo C, Myerson D, Leisenring WM, et al. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood. 2003;102(1):394-403. Figure 1. Figure 1. Disclosures Hansen: Otsuka Pharma: Membership on an entity's Board of Directors or advisory committees. Grønbæk:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen Pharma: Membership on an entity's Board of Directors or advisory committees; Otsuka Pharma: Membership on an entity's Board of Directors or advisory committees.


2013 ◽  
Vol 37 ◽  
pp. S51-S52
Author(s):  
E. Verigou ◽  
N. Smyrni ◽  
G. Kolliopoulou ◽  
E. Hala ◽  
P. Lampropoulou ◽  
...  

2008 ◽  
Vol 129 (2) ◽  
pp. 300-308 ◽  
Author(s):  
Sepideh Maftoun-Banankhah ◽  
Atousa Maleki ◽  
Nitin J. Karandikar ◽  
Arnaldo A. Arbini ◽  
Franklin S. Fuda ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e44321 ◽  
Author(s):  
Sergio Matarraz ◽  
Cristina Teodosio ◽  
Carlos Fernandez ◽  
Manuel Albors ◽  
María Jara-Acevedo ◽  
...  

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