Skip to main content
Top
Published in: Annals of Hematology 7/2017

Open Access 01-07-2017 | Original Article

Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance

Authors: Louise de Swart, Alex Smith, Marius MacKenzie, Argiris Symeonidis, Judith Neukirchen, Dana Mikulenková, Teresa Vallespí, Gina Zini, Malgorzata Paszkowska-Kowalewska, Anton Kruger, Leonie Saft, Pierre Fenaux, David Bowen, Eva Hellström-Lindberg, Jaroslav Čermák, Reinhard Stauder, Aurelia Tatic, Mette Skov Holm, Luca Malcovati, Krzysztof Mądry, Jackie Droste, Nicole Blijlevens, Theo de Witte, Ulrich Germing

Published in: Annals of Hematology | Issue 7/2017

Login to get access

Abstract

The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard to the assessment of the MDS subtype. In order to ensure that correct diagnoses were made by the participating centres, blood and bone marrow slides of 10% of the first 1000 patients were reviewed by an 11-person panel of cytomorphologists. All slides were rated by at least 3 panel members (median 8 panel members; range 3–9). Marrow slides from 98 out of 105 patients were of good quality and therefore could be rated properly according to the WHO 2001 classification, including assessment of dysplastic lineages. The agreement between the reviewers whether the diagnosis was MDS or non-MDS was strong with an intra-class correlation coefficient (ICC) of 0.85. Six cases were detected not to fit the entry criteria of the registry, because they were diagnosed uniformly as CMML or AML by the panel members. The agreement by WHO 2001 classification was strong as well (ICC = 0.83). The concordance of the assessment of dysplastic lineages was substantial for megakaryopoiesis and myelopoiesis and moderate for erythropoiesis. Our data show that in general, the inter-observer agreement was high and a very low percentage of misdiagnosed cases had been entered into the EUMDS registry. Further studies including histomorphology are warranted.
Literature
2.
go back to reference Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D (2012) Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120(12):2454–2465CrossRefPubMedPubMedCentral Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, Le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SM, Miyazaki Y, Pfeilstöcker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D (2012) Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120(12):2454–2465CrossRefPubMedPubMedCentral
3.
go back to reference Westers TM, Cremers EM, Oelschlaegel U, Johansson U, Bettelheim P, Matarraz S, Orfao A, Moshaver B, Brodersen LE, Loken MR, Wells DA, Subirá D, Cullen M, Te Marvelde JG, van der Velden VH, Preijers FW, Chu SC, Feuillard J, Guérin E, Psarra K, Porwit A, Saft L, Ireland R, Milne T, Béné MC, Witte BI, Della Porta MG, Kern W, van de Loosdrecht AA, IMDSFlow Working Group (2017) Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group. Haematologica 102(2):308–319. doi:10.3324/haematol.2016.147835 CrossRefPubMedPubMedCentral Westers TM, Cremers EM, Oelschlaegel U, Johansson U, Bettelheim P, Matarraz S, Orfao A, Moshaver B, Brodersen LE, Loken MR, Wells DA, Subirá D, Cullen M, Te Marvelde JG, van der Velden VH, Preijers FW, Chu SC, Feuillard J, Guérin E, Psarra K, Porwit A, Saft L, Ireland R, Milne T, Béné MC, Witte BI, Della Porta MG, Kern W, van de Loosdrecht AA, IMDSFlow Working Group (2017) Immunophenotypic analysis of erythroid dysplasia in myelodysplastic syndromes. A report from the IMDSFlow working group. Haematologica 102(2):308–319. doi:10.​3324/​haematol.​2016.​147835 CrossRefPubMedPubMedCentral
4.
go back to reference Bejar R, Stevenson KE, Caughey BA, Abdel-Wahab O, Steensma DP, Galili N, Raza A, Kantarjian H, Levine RL, Neuberg D, Garcia-Manero G, Ebert BL (2012) Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes. J Clin Oncol 30(27):3376–3382. doi:10.1200/JCO.2011.40.7379 CrossRefPubMedPubMedCentral Bejar R, Stevenson KE, Caughey BA, Abdel-Wahab O, Steensma DP, Galili N, Raza A, Kantarjian H, Levine RL, Neuberg D, Garcia-Manero G, Ebert BL (2012) Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes. J Clin Oncol 30(27):3376–3382. doi:10.​1200/​JCO.​2011.​40.​7379 CrossRefPubMedPubMedCentral
5.
go back to reference Malcovati L, Hellstrom-Lindberg E, Bowen D, Adès L, Cermak J, Del Cañizo C, Della Porta MG, Fenaux P, Gattermann N, Germing U, Jansen JH, Mittelman M, Mufti G, Platzbecker U, Sanz GF, Selleslag D, Skov-Holm M, Stauder R, Symeonidis A, van de Loosdrecht AA, de Witte T, Cazzola M, Net EL (2013) Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood 122(17):2943–2964. doi:10.1182/blood-2013-03-492884 CrossRefPubMedPubMedCentral Malcovati L, Hellstrom-Lindberg E, Bowen D, Adès L, Cermak J, Del Cañizo C, Della Porta MG, Fenaux P, Gattermann N, Germing U, Jansen JH, Mittelman M, Mufti G, Platzbecker U, Sanz GF, Selleslag D, Skov-Holm M, Stauder R, Symeonidis A, van de Loosdrecht AA, de Witte T, Cazzola M, Net EL (2013) Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood 122(17):2943–2964. doi:10.​1182/​blood-2013-03-492884 CrossRefPubMedPubMedCentral
6.
go back to reference de Swart L, Smith A, Johnston TW, Haase D, Droste J, Fenaux P, Symeonidis A, Sanz G, Hellström-Lindberg E, Cermák J, Germing U, Stauder R, Georgescu O, MacKenzie M, Malcovati L, Holm MS, Almeida AM, Mądry K, Slama B, Guerci-Bresler A, Sanhes L, Beyne-Rauzy O, Luño E, Bowen D, de Witte T (2015) Validation of the revised international prognostic scoring system (IPSS-R) in patients with lower-risk myelodysplastic syndromes: a report from the prospective European LeukaemiaNet MDS (EUMDS) registry. Br J Haematol 170(3):372–383. doi:10.1111/bjh.13450 CrossRefPubMed de Swart L, Smith A, Johnston TW, Haase D, Droste J, Fenaux P, Symeonidis A, Sanz G, Hellström-Lindberg E, Cermák J, Germing U, Stauder R, Georgescu O, MacKenzie M, Malcovati L, Holm MS, Almeida AM, Mądry K, Slama B, Guerci-Bresler A, Sanhes L, Beyne-Rauzy O, Luño E, Bowen D, de Witte T (2015) Validation of the revised international prognostic scoring system (IPSS-R) in patients with lower-risk myelodysplastic syndromes: a report from the prospective European LeukaemiaNet MDS (EUMDS) registry. Br J Haematol 170(3):372–383. doi:10.​1111/​bjh.​13450 CrossRefPubMed
7.
go back to reference Bennett JM (2000) World Health Organization classification of the acute leukemias and myelodysplastic syndrome. Int J Hematol 72(2):131–133PubMed Bennett JM (2000) World Health Organization classification of the acute leukemias and myelodysplastic syndrome. Int J Hematol 72(2):131–133PubMed
8.
go back to reference Brunning RD, Bennett JM, Flandrin G, Matutes E, Head D, Varidman JW, Harris NL (2001) Myelodysplastic syndromes. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) Pathology and genetics of Tumours of Haematopoietic and lymphoid tissues. IARC press, Lyon, pp 61–74 Brunning RD, Bennett JM, Flandrin G, Matutes E, Head D, Varidman JW, Harris NL (2001) Myelodysplastic syndromes. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) Pathology and genetics of Tumours of Haematopoietic and lymphoid tissues. IARC press, Lyon, pp 61–74
9.
go back to reference Shrout PE, FLeiss JL (1979) Intraclass correlation: uses in assessing rater reliability. Psychol Bull 86(2):420–428CrossRefPubMed Shrout PE, FLeiss JL (1979) Intraclass correlation: uses in assessing rater reliability. Psychol Bull 86(2):420–428CrossRefPubMed
10.
go back to reference Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174CrossRefPubMed Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174CrossRefPubMed
11.
go back to reference Valent P, Horny HP, Bennett JM, Fonatsch C, Germing U, Greenberg P, Haferlach T, Haase D, Kolb HJ, Krieger O, Loken M, van de Loosdrecht A, Ogata K, Orfao A, Pfeilstöcker M, Rüter B, Sperr WR, Stauder R, Wells DA (2007) Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res 31(6):727–736CrossRefPubMed Valent P, Horny HP, Bennett JM, Fonatsch C, Germing U, Greenberg P, Haferlach T, Haase D, Kolb HJ, Krieger O, Loken M, van de Loosdrecht A, Ogata K, Orfao A, Pfeilstöcker M, Rüter B, Sperr WR, Stauder R, Wells DA (2007) Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res 31(6):727–736CrossRefPubMed
12.
13.
go back to reference Font P, Loscertales J, Soto C, Ricard P, Novas CM, Martín-Clavero E, López-Rubio M, Garcia-Alonso L, Callejas M, Bermejo A, Benavente C, Ballesteros M, Cedena T, Calbacho M, Urbina R, Villarrubia J, Gil S, Bellón JM, Diez-Martin JL, Villegas A (2015) Interobserver variance in myelodysplastic syndromes with less than 5% bone marrow blasts: unilineage vs. multilineage dysplasia and reproducibility of the threshold of 2% blasts. Ann Hematol 94(4):565–573. doi:10.1007/s00277-014-2252-4 CrossRefPubMed Font P, Loscertales J, Soto C, Ricard P, Novas CM, Martín-Clavero E, López-Rubio M, Garcia-Alonso L, Callejas M, Bermejo A, Benavente C, Ballesteros M, Cedena T, Calbacho M, Urbina R, Villarrubia J, Gil S, Bellón JM, Diez-Martin JL, Villegas A (2015) Interobserver variance in myelodysplastic syndromes with less than 5% bone marrow blasts: unilineage vs. multilineage dysplasia and reproducibility of the threshold of 2% blasts. Ann Hematol 94(4):565–573. doi:10.​1007/​s00277-014-2252-4 CrossRefPubMed
14.
go back to reference Font P, Loscertales J, Benavente C, Bermejo A, Callejas M, Garcia-Alonso L, Garcia-Marcilla A, Gil S, Lopez-Rubio M, Martin E, Muñoz C, Ricard P, Soto C, Balsalobre P, Villegas A (2013) Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification. Ann Hematol 92(1):19–24. doi:10.1007/s00277-012-1565-4 CrossRefPubMed Font P, Loscertales J, Benavente C, Bermejo A, Callejas M, Garcia-Alonso L, Garcia-Marcilla A, Gil S, Lopez-Rubio M, Martin E, Muñoz C, Ricard P, Soto C, Balsalobre P, Villegas A (2013) Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification. Ann Hematol 92(1):19–24. doi:10.​1007/​s00277-012-1565-4 CrossRefPubMed
16.
go back to reference Cremers EM, Westers TM, Alhan C, Cali C, Visser-Wisselaar HA, Chitu DA, van der Velden VH, Te Marvelde JG, Klein SK, Muus P, Vellenga E, de Greef GE, Legdeur MC, Wijermans PW, Stevens-Kroef MJ, Silva-Coelho PD, Jansen JH, Ossenkoppele GJ, van de Loosdrecht AA, A study on behalf of the HOVON89 study group (2017) Implementation of erythroid lineage analysis by flow cytometry in diagnostic models for myelodysplastic syndromes. Haematologica 102(2):320–326. doi:10.3324/haematol.2016.147843 CrossRefPubMedPubMedCentral Cremers EM, Westers TM, Alhan C, Cali C, Visser-Wisselaar HA, Chitu DA, van der Velden VH, Te Marvelde JG, Klein SK, Muus P, Vellenga E, de Greef GE, Legdeur MC, Wijermans PW, Stevens-Kroef MJ, Silva-Coelho PD, Jansen JH, Ossenkoppele GJ, van de Loosdrecht AA, A study on behalf of the HOVON89 study group (2017) Implementation of erythroid lineage analysis by flow cytometry in diagnostic models for myelodysplastic syndromes. Haematologica 102(2):320–326. doi:10.​3324/​haematol.​2016.​147843 CrossRefPubMedPubMedCentral
17.
go back to reference Cremers EM, Westers TM, Alhan C, Cali C, Wondergem MJ, Poddighe PJ, Ossenkoppele GJ, van de Loosdrecht AA (2016) Multiparameter flow cytometry is instrumental to distinguish myelodysplastic syndromes from non-neoplastic cytopenias. Eur J Cancer 54:49–56. doi:10.1016/j.ejca.2015.11.013 CrossRefPubMed Cremers EM, Westers TM, Alhan C, Cali C, Wondergem MJ, Poddighe PJ, Ossenkoppele GJ, van de Loosdrecht AA (2016) Multiparameter flow cytometry is instrumental to distinguish myelodysplastic syndromes from non-neoplastic cytopenias. Eur J Cancer 54:49–56. doi:10.​1016/​j.​ejca.​2015.​11.​013 CrossRefPubMed
18.
go back to reference Germing U, Gattermann N, Strupp C, Aivado M, Aul C (2000) Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 24(12):983–992CrossRefPubMed Germing U, Gattermann N, Strupp C, Aivado M, Aul C (2000) Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 24(12):983–992CrossRefPubMed
19.
go back to reference Howe RB, Porwit-MacDonald A, Wanat R, Tehranchi R, Hellström-Lindberg E (2004) The WHO classification of MDS does make a difference. Blood 103(9):3265–3270CrossRefPubMed Howe RB, Porwit-MacDonald A, Wanat R, Tehranchi R, Hellström-Lindberg E (2004) The WHO classification of MDS does make a difference. Blood 103(9):3265–3270CrossRefPubMed
20.
go back to reference Germing U, Strupp C, Kuendgen A, Isa S, Knipp S, Hildebrandt B, Giagounidis A, Aul C, Gattermann N, Haas R (2006) Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica 91(12):1596–1604PubMed Germing U, Strupp C, Kuendgen A, Isa S, Knipp S, Hildebrandt B, Giagounidis A, Aul C, Gattermann N, Haas R (2006) Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica 91(12):1596–1604PubMed
21.
go back to reference Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405. doi:10.1182/blood-2016-03-643544 CrossRefPubMed Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405. doi:10.​1182/​blood-2016-03-643544 CrossRefPubMed
22.
go back to reference Mufti GJ, Bennett JM, Goasguen J, Bain BJ, Baumann I, Brunning R, Cazzola M, Fenaux P, Germing U, Hellström-Lindberg E, Jinnai I, Manabe A, Matsuda A, Niemeyer CM, Sanz G, Tomonaga M, Vallespi T, Yoshimi A, International Working Group on Morphology of Myelodysplastic Syndrome (2008) Diagnosis and classification of myelodysplastic syndrome: international working group on morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica 93(11):1712–1717. doi:10.3324/haematol.13405 CrossRefPubMed Mufti GJ, Bennett JM, Goasguen J, Bain BJ, Baumann I, Brunning R, Cazzola M, Fenaux P, Germing U, Hellström-Lindberg E, Jinnai I, Manabe A, Matsuda A, Niemeyer CM, Sanz G, Tomonaga M, Vallespi T, Yoshimi A, International Working Group on Morphology of Myelodysplastic Syndrome (2008) Diagnosis and classification of myelodysplastic syndrome: international working group on morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica 93(11):1712–1717. doi:10.​3324/​haematol.​13405 CrossRefPubMed
24.
go back to reference Brunning RD, Orazi A, Germing U, LeBeau MM, Porwit A, Baumann I, Vardiman JW, Hellstrom-Lindberg E (2008) Myelodysplastic syndromes/neoplasms, overview. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of Tumours of Haematopoietic and lymphoid tissues, 4th edn. IARC press, Lyon Brunning RD, Orazi A, Germing U, LeBeau MM, Porwit A, Baumann I, Vardiman JW, Hellstrom-Lindberg E (2008) Myelodysplastic syndromes/neoplasms, overview. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of Tumours of Haematopoietic and lymphoid tissues, 4th edn. IARC press, Lyon
25.
go back to reference Schemenau J, Baldus S, Anlauf M, Reinecke P, Braunstein S, Blum S, Nachtkamp K, Neukirchen J, Strup C, Aul C, Haas R, Gattermann N, Germing U (2015) Cellularity, characteristics of hematopoietic parameters and prognosis in myelodysplastic syndromes. Eur J Haematol 95(3):181–189. doi:10.1111/ejh.12512 CrossRefPubMed Schemenau J, Baldus S, Anlauf M, Reinecke P, Braunstein S, Blum S, Nachtkamp K, Neukirchen J, Strup C, Aul C, Haas R, Gattermann N, Germing U (2015) Cellularity, characteristics of hematopoietic parameters and prognosis in myelodysplastic syndromes. Eur J Haematol 95(3):181–189. doi:10.​1111/​ejh.​12512 CrossRefPubMed
Metadata
Title
Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance
Authors
Louise de Swart
Alex Smith
Marius MacKenzie
Argiris Symeonidis
Judith Neukirchen
Dana Mikulenková
Teresa Vallespí
Gina Zini
Malgorzata Paszkowska-Kowalewska
Anton Kruger
Leonie Saft
Pierre Fenaux
David Bowen
Eva Hellström-Lindberg
Jaroslav Čermák
Reinhard Stauder
Aurelia Tatic
Mette Skov Holm
Luca Malcovati
Krzysztof Mądry
Jackie Droste
Nicole Blijlevens
Theo de Witte
Ulrich Germing
Publication date
01-07-2017
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 7/2017
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-017-3009-7

Other articles of this Issue 7/2017

Annals of Hematology 7/2017 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine