The WHO diagnostic criteria for polycythemia vera—role of red cell mass versus hemoglobin/hematocrit level and morphology
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Regarding diagnosis of polycythemia vera (PV), discussion persists about hemoglobin (Hb) and/or hematocrit (Hct) threshold values as surrogate markers for red cell mass (RCM) and the diagnostic impact of bone marrow (BM) morphology. We performed a retrospective study on 290 patients with PV (151 males, 139 females; median age 65 years) presenting with characteristic BM features (initial biopsies, centralized evaluation) and endogenous erythroid colony (EEC) formations. This cohort included (1) a group of 229 patients when following the 2008 versus 256 patients diagnosed according to the 2016 World Health Organization (WHO) guidelines, all presented with increased RCM; (2) masked PV patients with low Hb (n = 143)/Hct (n = 45) recruited from the 2008 WHO cohort; (3) a cohort of 17 PV patients with elevated diagnostic Hb/Hct levels but low RCM; and (4) nine PV patients with increased RCM, opposing low Hb/Hct values. All patients were treated according to current PV guidelines (phlebotomies 87%, hydroxyurea 79%, and acetylsalicylic acid 87%). Applying the 2016 WHO criteria significantly increased concordance between RCM and Hb values compared with the 2008 WHO criteria (90 vs. 43% in males and 83 vs. 64% in females). Further analysis of the WHO 2016 PV cohort revealed that increased RCM is associated with increased Hb/Hct (93.8/94.6%). Our study supports and extends the diagnostic impact of the 2016 revised WHO classification for PV by highlighting the importance of characteristic BM findings and implies that Hb/Hct threshold values may be used as surrogate markers for RCM measurements.
KeywordsPolycythemia vera Red cell mass Clinical criteria Bone marrow morphology Masked polycythemia vera WHO classification 2016
This study was conducted under the aegis of CEMPO (Central European Myeloproliferative Organization) which provided the necessary conditions to make it possible.
M.G., L.J., J.T., and H.G. designed the research, contributed patients, participated in data analysis and interpretation, and wrote the paper. I.S. performed the statistical analysis, D.S. the EEC assays, and M.T. the RCM measurements. J.T., L.J., Ch.B.-Sch., and I.S.-K reviewed all bone marrow biopsies. All other authors either contributed patients or participated in reviewing bone marrow morphology.
Compliance with ethical standards
This study was conducted in accordance with the International Conference on Harmonization guidelines for Good Clinical Practice. The clinical study protocol was approved by the Institutional Ethical Committee of the Clinical Center of Serbia, No. 195/11, Date 24.11.2016.
All patients provided written informed consent in accordance with the Declaration of Helsinki prior to study participation.
Conflict of interest
None of the authors have any conflict of interest to disclose with regard to the current manuscript. All of the authors read and approved the final draft.
- 5.Alvarez-Larran A, Ancochea A, Angona A, Carme P, Garcia-Pallarols F, Martinez-Aviles L, Bellosillo B, Besses C (2012) Red cell mass measurement in patients with clinically suspected diagnosis of polycythemia vera or essential thrombocythemia. Haematologica 97(11):1704–1707CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (eds) (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. (revised 4th edition). International Agency for Research on Cancer, LyonGoogle Scholar
- 11.Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD (2009) The 2008 revision of the WHO classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114(5):937–951CrossRefPubMedGoogle Scholar
- 13.Barbui T, Thiele J, Gisslinger H, Finazzi G, Carobbio A, Rumi E, Luigia Randi M, Betozzi I, Vannucchi AM, Pieri L, Carrai V, Gisslinger B, Mullauer L, Ruggeri M, Rambaldi A, Tefferi A (2014) Masked polycythemia vera (mPV): results of an international study. Am J Hematol 89(1):52–54CrossRefPubMedGoogle Scholar
- 18.Madelung AB, Bondo H, Stamp I, Loevgreen P, Nielsen SL, Falensteen A, Knudsen H, Ehinger M, Dahl-Sorensen MNB, Svendsen KD, Lange T, Ralfkiaer E, Nielsen K, Hasselbalch HC, Thiele J (2013) World Health Organization-defined classification of myeloproliferative neoplasms: morphological reproducibility and clinical correlations—the Danish experience. Am J Hematol 88(12):1012–1016CrossRefPubMedGoogle Scholar
- 20.International Committee for Standardization in Haematology (1980) Recommended methods for measurement of red-cell and plasma volume. J Nucl Med 21(8):793–800Google Scholar
- 21.Pearson TC, Guthrie DL, Simpson J, Chinn S, Barosi G, Ferrant A, Lewis SJ, Najean Y (1995) Interpretation of measured red cell mass and plasma volume in adults: expert panel on radionuclides of the International Council for Standardization in Haematology. Br J Haematol 89(4):748–756CrossRefPubMedGoogle Scholar
- 22.Todorovic-Tirnanic M, Pavlovic S, Obradovic V, Elezovic I, Marisavljevic D, Miljic P, Milosevic RA, Bogdanovic AD, Bosnjakovic VB (2004) Clinical significance of optimal red cell mass and plasma volume estimation methods. Nucl Med Rev 7(1):31–38Google Scholar
- 23.Jaffe ES, Harris NLSH, Vardiman JW (eds) (2001) World Health Organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. International Agency for Research on Cancer, LyonGoogle Scholar
- 24.Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F, Randi ML, Vaidya R, Cazzola M, Rambaldi A, Gisslinger B, Pieri L, Ruggeri M, Bertozzi I, Sulai NH, Casetti I, Carobbio A, Jeryczynski G, Larson DR, Müllauer L, Pardanani A, Thiele J, Passamonti F, Barbui T (2013) Survival and prognosis among 1,545 patients with contemporary polycythemia vera: an international study. Leukemia 27(9):1874–1188CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Vannucchi AM, Grossi A, Pancrazzi A, Antonioli E, Guglielmelli P, Balestri F, Biscardi M, Bulgarelli S, Longo G, Graziano C, Gugliotta L, Bosi A (2004) PRV-1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemia. Br J Haematol 127(2):214–219CrossRefPubMedGoogle Scholar
- 31.Kvasnicka HM, Orazi A, Thiele J, Barosi G, Bueso-Ramos CE, Vannucchi AM, Hasserjian RP, Kiladjian JJ, Gianelli U, Silver R, Mughal TI, Barbui T (2017) European leukemia net study on the reproducibility of bone marrow features in masked polycythemia vera and differentiation from essential thrombocythemia. Am J Hematol 92(10):1062–1067CrossRefPubMedGoogle Scholar
- 33.Gianelli U, Iurlo A, Vener C, Moro A, Fermo E, Bianchi P, Graziani D, Radelli F, Coggi G, Bosari S, Delillers GL, Zanella A (2008) The significance of bone marrow biopsy and JAK2V617F mutation in the differential diagnosis between the “early” prepolycythemic phase of polycythemia vera and essential thrombocythemia. Am J Clin Pathol 30(3):336–342CrossRefGoogle Scholar
- 36.Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, De Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisis RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T, CYTO-PV Collaborative Group (2013) Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 368(1):22–33CrossRefPubMedGoogle Scholar