Download PDF
Semin Thromb Hemost 2006; 32(4): 362-371
DOI: 10.1055/s-2006-942757
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Impact of Clinicopathological Studies on Staging and Survival in Essential Thrombocythemia, Chronic Idiopathic Myelofibrosis, and Polycythemia Rubra Vera

Hans Michael Kvasnicka1 , Juergen Thiele1
  • 1Institute of Pathology, University of Cologne, Cologne, Germany
Further Information

Publication History

Publication Date:
29 June 2006 (online)

    Permissions and Reprints

ABSTRACT

In chronic myeloproliferative disorders (MPDs), varying results regarding staging of disease and assessment of outcome have been reported. Risk classification is mainly based on clinical data; however, in those disorders associated with an elevated platelet count, discrimination of (true) essential thrombocythemia (ET) may be difficult without the possibility to recognize characteristic histopathological bone marrow patterns according to the World Health Organization (WHO) guidelines. Patients with ET reveal no relevant reduction of life expectancy and the impact of disease is significantly higher in elderly patients, especially in chronic idiopathic myelofibrosis (IMF) and polycythemia rubra vera (PV). In high-risk ET, the overall incidence of myelofibrotic transformation after 36 months of follow-up is 2.8% when considering the Polycythemia Vera Study Group guidelines. In contrast, classification according to WHO fails to show a relevant transformation into myelofibrosis either by clinical or morphological standards in (true) ET. Early stages of IMF show a more favorable outcome, but in multivariate risk classification, signs of myeloid metaplasia have the most important impact on prognosis. In PV, the risk for thrombosis increases with age, and furthermore, signs of generalization are generally associated with a worsening of prognosis. It has been shown that examination of bone marrow specimens enhances the diagnostic reliability and also enables the recognition of evolving myelofibrotic transformation in MPDs.

KEYWORDS

Essential thrombocythemia - chronic idiopathic myelofibrosis - polycythemia rubra vera - survival - myelofibrotic transformation - bone marrow histopathology

REFERENCES

  • 1 Kvasnicka H M, Thiele J, Schmitt-Graeff A, Schaefer H E. Prognostic factors and survival in chronic myeloproliferative disorders.  Pathologe. 2000;  21 63-72
    CrossrefPubMedGoogle Scholar
  • 2 Kvasnicka H M, Thiele J, Werden C, Zankovich R, Diehl V, Fischer R. Prognostic factors in idiopathic (primary) osteomyelofibrosis.  Cancer. 1997;  80 708-719
    CrossrefPubMedGoogle Scholar
  • 3 Thiele J, Kvasnicka H M, Orazi A. Bone marrow histopathology in myeloproliferative disorders-current diagnostic approach.  Semin Hematol. 2005;  42 184-195
    CrossrefPubMedGoogle Scholar
  • 4 Vardiman J W, Pierre R, Thiele J, Imbert M. Chronic myeloproliferative disorders. In: Jaffe ES, Harris NL, Stein H, Vardiman JW WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France; IARC Press 2001: 16-59
    Google Scholar
  • 5 Gruppo Italiano Studio Policitemia . Polycythemia vera: the natural history of 1213 patients followed for 20 years.  Ann Intern Med. 1995;  123 656-664
    PubMedGoogle Scholar
  • 6 Passamonti F, Rumi E, Pungolino E et al.. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia.  Am J Med. 2004;  117 755-761
    CrossrefPubMedGoogle Scholar
  • 7 Visani G, Finelli C, Castelli U et al.. Myelofibrosis with myeloid metaplasia: clinical and haematological parameters predicting survival in a series of 133 patients.  Br J Haematol. 1990;  75 4-9
    CrossrefPubMedGoogle Scholar
  • 8 Bazzan M, Tamponi G, Schinco P et al.. Thrombosis-free survival and life expectancy in 187 consecutive patients with essential thrombocythemia.  Ann Hematol. 1999;  78 539-543
    CrossrefPubMedGoogle Scholar
  • 9 Mesa R A, Silverstein M N, Jacobsen S J, Wollan P C, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995.  Am J Hematol. 1999;  61 10-15
    CrossrefPubMedGoogle Scholar
  • 10 Passamonti F, Malabarba L, Orlandi E et al.. Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia.  Haematologica. 2003;  88 13-18
    PubMedGoogle Scholar
  • 11 Rozman C, Giralt M, Feliu E, Rubio D, Cortes M T. Life expectancy of patients with chronic nonleukemic myeloproliferative disorders.  Cancer. 1991;  67 2658-2663
    PubMedGoogle Scholar
  • 12 Kreft A, Weiss M, Wiese B et al.. Chronic idiopathic myelofibrosis: prognostic impact of myelofibrosis and clinical parameters on event-free survival in 122 patients who presented in prefibrotic and fibrotic stages. A retrospective study identifying subgroups of different prognoses by using the RECPAM method.  Ann Hematol. 2003;  82 605-611
    CrossrefPubMedGoogle Scholar
  • 13 Kvasnicka H M, Thiele J, Regn C, Zankovich R, Diehl V, Fischer R. Prognostic impact of apoptosis and proliferation in idiopathic (primary) myelofibrosis.  Ann Hematol. 1999;  78 65-72
    CrossrefPubMedGoogle Scholar
  • 14 Strasser-Weippl K, Steurer M, Kees M et al.. Age and hemoglobin level emerge as most important clinical prognostic parameters in patients with osteomyelofibrosis: introduction of a simplified prognostic score.  Leuk Lymphoma. 2006;  47 441-450
    CrossrefPubMedGoogle Scholar
  • 15 Hakulinen T. Cancer survival corrected for heterogeneity in patient withdrawal.  Biometrics. 1982;  38 933-942
    CrossrefPubMedGoogle Scholar
  • 16 Hakama M, Hakulinen T. Estimating the expectation of life in cancer survival studies with incomplete follow-up information.  J Chronic Dis. 1977;  30 585-597
    CrossrefPubMedGoogle Scholar
  • 17 Michiels J J. Normal life expectancy and thrombosis-free survival in aspirin treated essential thrombocythemia.  Clin Appl Thromb Hemost. 1999;  5 30-36
    PubMedGoogle Scholar
  • 18 Imbert M, Pierre R, Thiele J, Vardiman J W, Brunning R D, Flandrin G. Essential thrombocythaemia. In: Jaffe ES, Harris NL, Stein H, Vardiman JW WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France; IARC Press 2001: 39-41
    Google Scholar
  • 19 Thiele J, Kvasnicka H M. A critical reappraisal of the WHO classification of the chronic myeloproliferative disorders.  Leuk Lymphoma. 2006;  47 381-396
    CrossrefPubMedGoogle Scholar
  • 20 Murphy S. Diagnostic criteria and prognosis in polycythemia vera and essential thrombocythemia.  Semin Hematol. 1999;  36 9-13
    PubMedGoogle Scholar
  • 21 Michiels J J, Thiele J. Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia).  Int J Hematol. 2002;  76 133-145
    PubMedGoogle Scholar
  • 22 Thiele J, Kvasnicka H M, Zankovich R, Diehl V. Relevance of bone marrow features in the differential diagnosis between essential thrombocythemia and early stage idiopathic myelofibrosis.  Haematologica. 2000;  85 1126-1134
    PubMedGoogle Scholar
  • 23 Thiele J, Kvasnicka H M. Diagnostic differentiation of essential thrombocythaemia from thrombocythaemias associated with chronic idiopathic myelofibrosis by discriminate analysis of bone marrow features-a clinicopathological study on 272 patients.  Histol Histopathol. 2003;  18 93-102
    PubMedGoogle Scholar
  • 24 Thiele J, Imbert M, Pierre R, Vardiman J W, Brunning R D, Flandrin G. Chronic idiopathic myelofibrosis. In: Jaffe ES, Harris NL, Stein H, Vardiman JW WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues; Lyon, France IARC Press; 2001: 35-38
  • 25 Thiele J, Kvasnicka H M, Fischer R. Histochemistry and morphometry on bone marrow biopsies in chronic myeloproliferative disorders-aids to diagnosis and classification.  Ann Hematol. 1999;  78 495-506
    CrossrefPubMedGoogle Scholar
  • 26 Cervantes F, Alvarez-Larran A, Talarn C, Gomez M, Montserrat E. Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients.  Br J Haematol. 2002;  118 786-790
    CrossrefPubMedGoogle Scholar
  • 27 Harrison C N, Campbell P J, Buck G et al.. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.  N Engl J Med. 2005;  353 33-45
    CrossrefPubMedGoogle Scholar
  • 28 Harrison C N. Essential thrombocythaemia: challenges and evidence-based management.  Br J Haematol. 2005;  130 153-165
    CrossrefPubMedGoogle Scholar
  • 29 Kreft A, Buche G, Ghalibafian M, Buhr T, Fischer T, Kirkpatrick C J. The incidence of myelofibrosis in essential thrombocythaemia, polycythaemia vera and chronic idiopathic myelofibrosis: a retrospective evaluation of sequential bone marrow biopsies.  Acta Haematol. 2005;  113 137-143
    CrossrefPubMedGoogle Scholar
  • 30 Tefferi A. Recent progress in the pathogenesis and management of essential thrombocythemia.  Leuk Res. 2001;  25 369-377
    CrossrefPubMedGoogle Scholar
  • 31 Thiele J, Kvasnicka H M, Schmitt-Graeff A, Zankovich R, Diehl V. Follow-up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): a retrospective clinicopathological study of 120 patients.  Am J Hematol. 2002;  70 283-291
    CrossrefPubMedGoogle Scholar
  • 32 Barosi G, Ambrosetti A, Finelli C et al.. The Italian consensus conference on diagnostic criteria for myelofibrosis with myeloid metaplasia.  Br J Haematol. 1999;  104 730-737
    CrossrefPubMedGoogle Scholar
  • 33 Van de Pette J E, Prochazka A V, Pearson T C, Singh A K, Dickson E R, Wetherley-Mein G. Primary thrombocythaemia treated with busulphan.  Br J Haematol. 1986;  62 229-237
    PubMedGoogle Scholar
  • 34 Pearson T C. Primary thrombocythaemia: diagnosis and management.  Br J Haematol. 1991;  78 145-148
    PubMedGoogle Scholar
  • 35 Murphy S, Peterson P, Iland H, Laszlo J. Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment.  Semin Hematol. 1997;  34 29-39
    PubMedGoogle Scholar
  • 36 Fenaux P, Simon M, Caulier M T, Lai J L, Goudemand J, Bauters F. Clinical course of essential thrombocythemia in 147 cases.  Cancer. 1990;  66 549-556
    PubMedGoogle Scholar
  • 37 Bellucci S, Janvier M, Tobelem G et al.. Essential thrombocythemias. Clinical evolutionary and biological data.  Cancer. 1986;  58 2440-2447
    PubMedGoogle Scholar
  • 38 Annaloro C, Lambertenghi Deliliers G, Oriani A et al.. Prognostic significance of bone marrow biopsy in essential thrombocythemia.  Haematologica. 1999;  84 17-21
    PubMedGoogle Scholar
  • 39 Barbui T, Finazzi G. When and how to treat essential thrombocythemia.  N Engl J Med. 2005;  353 85-86
    CrossrefPubMedGoogle Scholar
  • 40 Thiele J, Kvasnicka H M, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity.  Haematologica. 2005;  90 1128-1132
    PubMedGoogle Scholar
  • 41 Barosi G. Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines.  J Clin Oncol. 1999;  17 2954-2970
    PubMedGoogle Scholar
  • 42 Laszlo J. Myeloproliferative disorders (MPD): myelofibrosis, myelosclerosis, extramedullary hematopoiesis, undifferentiated MPD, and hemorrhagic thrombocythemia.  Semin Hematol. 1975;  12 409-432
    PubMedGoogle Scholar
  • 43 Thiele J, Kvasnicka H M, Boeltken B, Zankovich R, Diehl V, Fischer R. Initial (prefibrotic) stages of idiopathic (primary) myelofibrosis (IMF)-a clinicopathological study.  Leukemia. 1999;  13 1741-1748
    CrossrefPubMedGoogle Scholar
  • 44 Georgii A, Buhr T, Buesche G, Kreft A, Choritz H. Classification and staging of Ph-negative myeloproliferative disorders by histopathology from bone marrow biopsies.  Leuk Lymphoma. 1996;  22(suppl 1) 15-29
    PubMedGoogle Scholar
  • 45 Thiele J, Kvasnicka H M. Chronic myeloproliferative disorders with thrombocythemia: a comparative study of two classification systems (PVSG, WHO) on 839 patients.  Ann Hematol. 2003;  82 148-152
    PubMedGoogle Scholar
  • 46 Thiele J, Kvasnicka H M. Hematopathologic findings in chronic idiopathic myelofibrosis.  Semin Oncol. 2005;  32 380-394
    CrossrefPubMedGoogle Scholar
  • 47 Lengfelder E, Hochhaus A, Kronawitter U et al.. Should a platelet limit of 600 × 109/l be used as a diagnostic criterion in essential thrombocythaemia? An analysis of the natural course including early stages.  Br J Haematol. 1998;  100 15-23
    CrossrefPubMedGoogle Scholar
  • 48 Barbui T, Barosi G, Grossi A et al.. Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation.  Haematologica. 2004;  89 215-232
    PubMedGoogle Scholar
  • 49 Barbui T, Finazzi G. Management of essential thrombocythemia.  Crit Rev Oncol Hematol. 1999;  29 257-266
    PubMedGoogle Scholar
  • 50 Anger B, Seidler R, Haug U, Popp C, Heimpel H. Idiopathic myelofibrosis: a retrospective study of 103 patients.  Haematologica. 1990;  75 228-234
    PubMedGoogle Scholar
  • 51 Manoharan A, Smart R C, Pitney W R. Prognostic factors in myelofibrosis.  Pathology. 1982;  14 455-461
    PubMedGoogle Scholar
  • 52 Hasselbalch H C. Idiopathic myelofibrosis-an update with particular reference to clinical aspects and prognosis.  Int J Clin Lab Res. 1993;  23 124-138
    PubMedGoogle Scholar
  • 53 Varki A, Lottenberg R, Griffith R, Reinhard E. The syndrome of idiopathic myelofibrosis. A clinicopathologic review with emphasis on the prognostic variables predicting survival.  Medicine (Baltimore). 1983;  62 353-371
    PubMedGoogle Scholar
  • 54 Rupoli S, Da Lio L, Sisti S et al.. Primary myelofibrosis: a detailed statistical analysis of the clinicopathological variables influencing survival.  Ann Hematol. 1994;  68 205-212
    CrossrefPubMedGoogle Scholar
  • 55 Okamura T, Kinukawa N, Niho Y, Mizoguchi H. Primary chronic myelofibrosis: clinical and prognostic evaluation in 336 Japanese patients.  Int J Hematol. 2001;  73 194-198
    PubMedGoogle Scholar
  • 56 Reilly J T. Idiopathic myelofibrosis: pathogenesis, natural history and management.  Blood Rev. 1997;  11 233-242
    CrossrefPubMedGoogle Scholar
  • 57 Barosi G, Berzuini C, Liberato L N, Costa A, Polino G, Ascari E. A prognostic classification of myelofibrosis with myeloid metaplasia.  Br J Haematol. 1988;  70 397-401
    PubMedGoogle Scholar
  • 58 Cervantes F, Pereira A, Esteve J et al.. Identification of ‘short-lived' and ‘long-lived' patients at presentation of idiopathic myelofibrosis.  Br J Haematol. 1997;  97 635-640
    CrossrefPubMedGoogle Scholar
  • 59 Dupriez B, Morel P, Demory J L et al.. Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system.  Blood. 1996;  88 1013-1018
    PubMedGoogle Scholar
  • 60 Njoku O S, Lewis S M, Catovsky D, Gordon-Smith E C. Anaemia in myelofibrosis: its value in prognosis.  Br J Haematol. 1983;  54 79-89
    PubMedGoogle Scholar
  • 61 Ozen S, Ferhanoglu B, Senocak M, Tuzuner N. Idiopathic myelofibrosis (agnogenic myeloid metaplasia): clinicopathological analysis of 32 patients.  Leuk Res. 1997;  21 125-131
    CrossrefPubMedGoogle Scholar
  • 62 Reilly J T, Snowden J A, Spearing R L et al.. Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases.  Br J Haematol. 1997;  98 96-102
    CrossrefPubMedGoogle Scholar
  • 63 Demory J L, Dupriez B, Fenaux P et al.. Cytogenetic studies and their prognostic significance in agnogenic myeloid metaplasia: a report on 47 cases.  Blood. 1988;  72 855-859
    PubMedGoogle Scholar
  • 64 Passamonti F, Rumi E, Arcaini L et al.. Leukemic transformation of polycythemia vera: a single center study of 23 patients.  Cancer. 2005;  104 1032-1036
    CrossrefPubMedGoogle Scholar
  • 65 Anger B, Haug U, Seidler R, Heimpel H. Polycythemia vera. A clinical study of 141 patients.  Blut. 1989;  59 493-500
    PubMedGoogle Scholar
  • 66 Ania B J, Suman V J, Sobell J L, Codd M B, Silverstein M N, Melton III L J. Trends in the incidence of polycythemia vera among Olmsted County, Minnesota residents, 1935-1989.  Am J Hematol. 1994;  47 89-93
    PubMedGoogle Scholar
  • 67 Bilgrami S, Greenberg B R. Polycythemia rubra vera.  Semin Oncol. 1995;  22 307-326
    PubMedGoogle Scholar
  • 68 Ellis J T, Peterson P, Geller S A, Rappaport H. Studies of the bone marrow in polycythemia vera and the evolution of myelofibrosis and second hematologic malignancies.  Semin Hematol. 1986;  23 144-155
    PubMedGoogle Scholar
  • 69 Brandt L, Anderson H. Survival and risk of leukaemia in polycythaemia vera and essential thrombocythaemia treated with oral radiophosphorus: are safer drugs available?.  Eur J Haematol. 1995;  54 21-26
    PubMedGoogle Scholar
  • 70 Finazzi G, Caruso V, Marchioli R et al.. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study.  Blood. 2005;  105 2664-2670
    CrossrefPubMedGoogle Scholar
  • 71 Marchioli R, Finazzi G, Landolfi R et al.. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.  J Clin Oncol. 2005;  23 2224-2232
    CrossrefPubMedGoogle Scholar
  • 72 Thiele J, Kvasnicka H M. Diagnostic impact of bone marrow histopathology in polycythemia vera (PV).  Histol Histopathol. 2005;  20 317-328
    PubMedGoogle Scholar
  • 73 Najean Y, Rain J D, Dresch C et al.. Risk of leukaemia, carcinoma, and myelofibrosis in 32P- or chemotherapy-treated patients with polycythaemia vera: a prospective analysis of 682 cases. The “French Cooperative Group for the Study of Polycythaemias”.  Leuk Lymphoma. 1996;  suppl 1 111-119
    PubMedGoogle Scholar
  • 74 Najean Y, Rain J D, Billotey C. Epidemiological data in polycythaemia vera: a study of 842 cases.  Hematol Cell Ther. 1998;  40 159-165
    PubMedGoogle Scholar
  • 75 Spivak J L. Polycythemia vera: myths, mechanisms, and management.  Blood. 2002;  100 4272-4290
    CrossrefPubMedGoogle Scholar
  • 76 Nielsen I, Hasselbalch H C. Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan.  Am J Hematol. 2003;  74 26-31
    CrossrefPubMedGoogle Scholar
  • 77 Sterkers Y, Preudhomme C, Lai J L et al.. Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion.  Blood. 1998;  91 616-622
    PubMedGoogle Scholar
  • 78 Thiele J, Kvasnicka H M, Diehl V. Bone marrow features of diagnostic impact in erythrocytosis.  Ann Hematol. 2005;  84 362-367
    CrossrefPubMedGoogle Scholar
  • 79 Thiele J, Kvasnicka H M, Diehl V. Initial (latent) polycythemia vera with thrombocytosis mimicking essential thrombocythemia.  Acta Haematol. 2005;  113 213-219
    CrossrefPubMedGoogle Scholar
  • 80 Thiele J M, Kvasnicka H M. Diagnosis of polycythemia vera based on bone marrow pathology.  Curr Hematol Rep. 2005;  4 218-223
    PubMedGoogle Scholar

Hans Michael KvasnickaM.D. 

Institute for Pathology, University of Cologne

Joseph-Stelzmann-Str.9, D-50924 Cologne, Germany

Email: hm.kvasnicka@uni-koeln.de