Bone marrow histopathology in the diagnosis of chronic myeloproliferative disorders: A forgotten pearl

Best Practice and Research: Clinical Haematology

Volumn 19, Issue 3, 2006, Pages 413-437

  Thiele, J ^a   Kvasnicka, H M ^a   Vardiman, J ^b  

^a UNIVERSITY OF COLOGNE   (Germany)

^b UNIVERSITY OF CHICAGO   (United States)

Author keywords

bone marrow biopsies; chronic myelofibrosis; chronic myelogenous leukemia; dynamics; essential thrombocythemia; histological staging; polycythemia vera

Indexed keywords

ALPHA2B INTERFERON; ANAGRELIDE; BUSULFAN; CYTARABINE; CYTOSTATIC AGENT; HYDROXYUREA; IMATINIB; INTERFERON; RETICULIN;

ANTINEOPLASTIC ACTIVITY; BONE MARROW BIOPSY; CHRONIC MYELOID LEUKEMIA; CLINICAL FEATURE; CLINICAL TRIAL; DIAGNOSTIC ACCURACY; DIAGNOSTIC ERROR; DIAGNOSTIC VALUE; DIFFERENTIAL DIAGNOSIS; DISEASE CLASSIFICATION; DISEASE COURSE; DRUG EFFICACY; ERYTHROCYTOSIS; FOLLOW UP; HISTOPATHOLOGY; HUMAN; MYELOID METAPLASIA; MYELOPROLIFERATIVE DISORDER; POLYCYTHEMIA VERA; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; REVIEW; THROMBOCYTHEMIA;

BONE MARROW; HUMANS; LEUKEMIA, NEUTROPHILIC, CHRONIC; MYELOFIBROSIS; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA VERA; THROMBOCYTHEMIA, HEMORRHAGIC;

EID: 33745079673     PISSN: 15216926     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.beha.2005.07.015     Document Type: Review

References (103)

1. Dickstein J.I., and Vardiman J.W. Hematopathologic findings in the myeloproliferative disorders. Seminars in Oncology 22 (1995) 355-373
2. Vardiman JW, Pierre R, Thiele J & Imbert M. Chronic myeloproliferative disorders. In Jaffe ES, Harris NL, Stein H& Vardiman JW (eds) WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues., pp 16-59. Lyon: IARC Press, 2001.
3. Georgii T., Vykoupil KF., Buhr T., and Choritz H. myeloproliferative disorders in bone marrow biopsies. Pathology, Research and Practice 186 (1990) 3-27
4. Buhr T., Choritz H., and Georgii A. The impact of megakaryocyte proliferation of the evolution of myelofibrosis. Histological follow-up study in 186 patients with chronic myeloid leukaemia. Virchows Archiv A Pathology Anatomy Histopathology 420 (1992) 473-478
5. Bartl R., Frisch B., and Wilmanns W. Potential of bone marrow biopsy in chronic myeloproliferative disorders (MPD). European Journal of Haematology 50 (1993) 41-52
6. Dickstein J.I., and Vardiman J.W. Issues in the pathology and diagnosis of the chronic myeloproliferative disorders and the myelodysplastic syndromes. American Journal of Clinical Pathology 99 (1993) 513-525
7. Georgii A., Buesche G., and Kreft A. The histopathology of chronic myeloproliferative diseases. Baillieres Clinical Haematology 11 (1998) 721-749
8. Thiele J., Kvasnicka H.M., and Fischer R. Histochemistry and morphometry on bone marrow biopsies in chronic myeloproliferative disorders - aids to diagnosis and classification. Annals of Hematology 78 (1999) 495-506
9. Thiele J., Kvasnicka H.M., Schmitt-Graeff A., Zirbes T.K., et al. Bone marrow features and clinical findings in chronic myeloid leukemia-a comparative, multicenter, immunohistological and morphometric study on 614 patients. Leukemia & Lymphoma 36 (2000) 295-308
10. Buesche G., Hehlmann R., Hecker H., Heimpel H., et al. Marrow fibrosis, indicator of therapy failure in chronic myeloid leukemia - prospective long-term results from a randomized-controlled trial. Leukemia 17 (2003) 2444-2453
11. Sokal J.E., and Sheerin K.A. Decreased stainable marrow iron in chronic granulocytic leukemia. The American Journal of Medicine 81 (1986) 395-399
12. Hayhoe F.G., Flemans R.J., and Cowling D.C. Acquired lipidosis of marrow macrophages: birefringent blue crystals and Gaucher-like cells, sea-blue histiocytes, and grey-green crystals. Journal of Clinical Pathology 32 (1979) 420-428
13. Kelsey P.R., and Geary C.G. Sea-blue histiocytes and Gaucher cells in bone marrow of patients with chronic myeloid leukaemia. Journal of Clinical Pathology 41 (1988) 960-962
14. Schmid C., Frisch B., Beham A., Jager K., et al. Comparison of bone marrow histology in early chronic granulocytic leukemia and in leukemoid reaction. European Journal of Haematology 44 (1990) 154-158
15. Thiele J., Kvasnicka H.M., and Fischer R. Bone marrow histopathology in chronic myelogenous leukemia (CML)-evaluation of distinctive features with clinical impact. Histology and Histopathology 14 (1999) 1241-1256
16. Lazzarino M., Morra E., Castello A., Inverardi D., et al. Myelofibrosis in chronic granulocytic leukaemia: clinicopathologic correlations and prognostic significance. British Journal of Haematology 64 (1986) 227-240
17. Dekmezian R., Kantarjian H.M., Keating M.J., Talpaz M., et al. The relevance of reticulin stain-measured fibrosis at diagnosis in chronic myelogenous leukemia. Cancer 59 (1987) 1739-1743
18. 1+ chronic myelogenous leukaemia-a multicentre study on 495 patients. British Journal of Haematology 112 (2001) 727-739
19. Wilhelm M., Bueso-Ramos C., O'Brien S., Pierce S., et al. Effect of interferon-alpha therapy on bone marrow fibrosis in chronic myelogenous leukemia. Leukemia 12 (1998) 65-70
20. Thiele J., Kvasnicka H.M., Schmitt-Graeff A., Spohr M., et al. Effects of interferon and hydroxyurea on bone marrow fibrosis in chronic myelogenous leukaemia: a comparative retrospective multicentre histological and clinical study. British Journal of Haematology 108 (2000) 64-71
21. Thiele J., Kvasnicka H.M., Schmitt-Graeff A., Bundschuh S., et al. Effects of chemotherapy (busulfan-hydroxyurea) and interferon-alfa on bone marrow morphologic features in chronic myelogenous leukemia. Histochemical and morphometric study on sequential trephine biopsy specimens with special emphasis on dynamic features. American Journal of Clinical Pathology 114 (2000) 57-65
22. 1+ chronic myelogenous leukemia: a multicenter trial. Journal of Clinical Oncology 2001; 19: 2994-3009.
23. Thiele J., Kvasnicka H.M., Niederle N., Zirbes T.K., et al. The impact of interferon versus busulfan therapy on the reticulin stain-measured fibrosis in CML-a comparative morphometric study on sequential trephine biopsies. Annals of Hematology 70 (1995) 121-128
24. Straetmans N., Ma D.D., Nevell D.F., and Arthur C. Evolution of bone marrow fibrosis and stromal antigenic expression in chronic myeloid leukemia on alpha interferon and Ara-C therapy. Hematopathology and Molecular Hematology 10 (1996) 213-222
25. Sacchi S. The role of alpha-interferon in essential thrombocythaemia, polycythaemia vera and myelofibrosis with myeloid metaplasia (MMM): a concise update. Leukemia & Lymphoma 19 (1995) 13-20
26. Bachleitner-Hofmann T & Gisslinger H. The role of interferon-alpha in the treatment of idiopathic myelofibrosis. Annals of Hematology 1999; 78: 533-538.
27. Kreft A., Nolde C., Busche G., Buhr T., et al. Polycythaemia vera: bone marrow histopathology under treatment with interferon, hydroxyurea and busulphan. European Journal of Haematology 64 (2000) 32-41
28. Beham-Schmid C., Apfelbeck U., Sill H., Tsybrovsky O., et al. Treatment of chronic myelogenous leukemia with the tyrosine kinase inhibitor STI571 results in marked regression of bone marrow fibrosis. Blood 99 (2002) 381-383
29. Hasserjian R.P., Boecklin F., Parker S., Chase A., et al. ST1571 (imatinib mesylate) reduces bone marrow cellularity and normalizes morphologic features irrespective of cytogenetic response. American Journal of Clinical Pathology 117 (2002) 360-367
30. Bueso-Ramos C.E., Cortes J., Talpaz M., O'Brien S., et al. Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia. Cancer 101 (2004) 332-336
31. Thiele J., Kvasnicka H.M., Schmitt-Graeff A., Kriener S., et al. Effects of the tyrosine kinase inhibitor Imatinib mesylate (STI571) on bone marrow features in patients with chronic myelogenous leukemia. Histology and Histopathology 19 (2004) 1277-1288
32. Kvasnicka H.M., Thiele J., Staib P., Schmitt-Graeff A., et al. Reversal of bone marrow angiogenesis in chronic myeloid leukemia following imatinib mesylate (STI571) therapy. Blood 103 (2004) 3549-3551
33. Kvasnicka HM, Thiele J, Schmitt-Graeff A, Diehl V, et al. Impact of bone marrow morphology on multivariate risk classification in chronic myelogenous leukemia. Acta Haematologica 2003; 109: 53-56.
34. Thiele J., Kvasnicka H.M., Beelen D.W., Zirbes T.K., et al. Relevance and dynamics of myelofibrosis regarding hematopoietic reconstitution after allogeneic bone marrow transplantation in chronic myelogenous leukemia-a single center experience on 160 patients. Bone Marrow Transplantation 26 (2000) 275-281
35. Pearson T.C. Diagnosis and classification of erythrocytoses and thrombocytoses. Baillieres Clinical Haematology 11 (1998) 695-720
36. Pierre R, Imbert M, Thiele J, Vardiman JW, et al. Polycythaemia vera. In Jaffe ES, Harris NL, Stein H& Vardiman JW (eds) WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues., pp 32-38. Lyon: IARC Press, 2001.
37. Spivak J.L. Polycythemia vera: myths, mechanisms, and management. Blood 100 (2002) 4272-4290
38. Najean Y., Triebel F., and Dresch C. Pure erythrocytosis: reappraisal of a study of 51 cases. American Journal of Hematology 10 (1981) 129-136
39. Westwood N., Dudley J.M., Sawyer B., Messinezy M., et al. Primary polycythaemia: diagnosis by non-conventional positive criteria. European Journal of Haematology 51 (1993) 228-232
40. Messinezy M., Sawyer B., Westwood N.B., and Pearson T.C. Idiopathic erythrocytosis-additional new study techniques suggest a heterogenous group. European Journal of Haematology 53 (1994) 163-167
41. Ruggeri M., Tosetto A., Frezzato M., and Rodeghiero F. The rate of progression to polycythemia vera or essential thrombocythemia in patients with erythrocytosis or thrombocytosis. Annals of Internal Medicine 139 (2003) 470-475
42. Gruppo Italiano Studio Policitemia. Polycythemia vera: the natural history of 1213 patients followed for 20 years. Annals of Internal Medicine 1995; 123: 656-664.
43. Ellis J.T., Peterson P., Geller S.A., and Rappaport H. Studies of the bone marrow in polycythemia vera and the evolution of myelofibrosis and second hematologic malignancies. Seminars in Hematology 23 (1986) 144-155
44. Najean Y., Dresch C., and Rain J.D. The very-long-term course of polycythaemia: a complement to the previously published data of the Polycythaemia Vera Study Group. British Journal of Haematology 86 (1994) 233-235
45. Bilgrami S & Greenberg BR. Polycythemia rubra vera. Seminars in Oncology 1995; 22: 307-326.
46. Passamonti F., Malabarba L., Orlandi E., Barate C., et al. Polycythemia vera in young patients: a study on the long-term risk of thrombosis, myelofibrosis and leukemia. Haematologica 88 (2003) 13-18
47. Georgii A., Buhr T., Buesche G., Kreft A., et al. Classification and staging of Ph-negative myeloproliferative disorders by histopathology from bone marrow biopsies. Leukemia & Lymphoma 22 Suppl 1 (1996) 15-29
48. Thiele J., Kvasnicka H.M., Muehlhausen K., Walter S., et al. Polycythemia rubra vera versus secondary polycythemias. A clinicopathological evaluation of distinctive features in 199 patients. Pathology, Research and Practice 197 (2001) 77-84
49. Michiels J.J., and Thiele J. Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia). International Journal of Hematology 76 (2002) 133-145
50. Thiele J., and Kvasnicka H.M. Diagnostic impact of bone marrow histopathology in polycythemia vera (PV). Histology and Histopathology 20 (2005) 317-328
51. Ellis J.T., Silver R.T., Coleman M., and Geller S.A. The bone marrow in polycythemia vera. Seminars in Hematology 12 (1975) 433-444
52. Ellis J.T., and Peterson P. The bone marrow in polycythemia vera. Pathology Annual 14 Pt 1 (1979) 383-403
53. Thiele J., Kvasnicka H.M., Zankovich R., and Diehl V. The value of bone marrow histology in differentiating between early stage polycythemia vera and secondary (reactive) polycythemias. Haematologica 86 (2001) 368-374
54. Thiele J., Schneider G., Hoeppner B., Wienhold S., et al. Histomorphometry of bone marrow biopsies in chronic myeloproliferative disorders with associated thrombocytosis-features of significance for the diagnosis of primary (essential) thrombocythaemia. Virchows Archiv A Pathology Anatomy Histopathology 413 (1988) 407-417
55. Buhr T., Georgii A., Schuppan O., Amor A., et al. Histologic findings in bone marrow biopsies of patients with thrombocythemic cell counts. Annals of Hematology 64 (1992) 286-291
56. Thiele J., Kvasnicka H.M., Diehl V., Fischer R., et al. Clinicopathological diagnosis and differential criteria of thrombocythemias in various myeloproliferative disorders by histopathology, histochemistry and immunostaining from bone marrow biopsies. Leukemia & Lymphoma 33 (1999) 207-218
57. Thiele J, Kvasnicka HM & Diehl V. Standardization of bone marrow features - does it work in hematopathology for histological discrimination of different disease patterns? Histology and Histopathology 2005: 90: 1129-1133.
58. Shih L.Y., and Lee C.T. Identification of masked polycythemia vera from patients with idiopathic marked thrombocytosis by endogenous erythroid colony assay. Blood 83 (1994) 744-748
59. Jantunen R., Juvonen E., Ikkala E., Oksanen K., et al. Development of erythrocytosis in the course of essential thrombocythemia. Annals of Hematology 78 (1999) 219-222
60. Murphy S., Peterson P., Iland H., and Laszlo J. Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Seminars in Hematology 34 (1997) 29-39
61. Laszlo J. Myeloproliferative disorders (MPD): myelofibrosis, myelosclerosis, extramedullary hematopoiesis, undifferentiated MPD, and hemorrhagic thrombocythemia. Seminars in Hematology 12 (1975) 409-432
62. Wolf B.C., and Neiman R.S. Myelofibrosis with myeloid metaplasia: pathophysiologic implications of the correlation between bone marrow changes and progression of splenomegaly. Blood 65 (1985) 803-809
63. Buhr T., Georgii A., and Choritz H. Myelofibrosis in chronic myeloproliferative disorders. Incidence among subtypes according to the Hannover Classification. Pathology, Research and Practice 189 (1993) 121-132
64. Barosi G. Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines. Journal of Clinical Oncology 17 (1999) 2954-2970
65. Tefferi A. Myelofibrosis with myeloid metaplasia. The New England Journal of Medicine 342 (2000) 1255-1265
66. Dingli D., Mesa R.A., and Tefferi A. Myelofibrosis with myeloid metaplasia: new developments in pathogenesis and treatment. Internal Medicine 43 (2004) 540-547
67. Thiele J., Zankovich R., Steinberg T., Fischer R., et al. Agnogenic myeloid metaplasia (AMM) - correlation of bone marrow lesions with laboratory data: a longitudinal clinicopathological study on 114 patients. Hematological Oncology 7 (1989) 327-343
68. Thiele J., Kvasnicka H.M., Boeltken B., Zankovich R., et al. Initial (prefibrotic) stages of idiopathic (primary) myelofibrosis (IMF) - a clinicopathological study. Leukemia 13 (1999) 1741-1748
69. Thiele J & Kvasnicka HM. Prefibrotic chronic idiopathic myelofibrosis-a diagnostic enigma? Acta Haematologica 2004; 111: 155-159.
70. Buhr T., Buesche G., Choritz H., Langer F., et al. Evolution of myelofibrosis in chronic idiopathic myelofibrosis as evidenced in sequential bone marrow biopsy specimens. American Journal of Clinical Pathology 119 (2003) 152-158
71. Thiele J., Kvasnicka H.M., Schmitt-Gräff A., and Diehl V. Dynamics of fibrosis in chronic idiopathic (primary) myelofibrosis during therapy: a follow-up study on 309 patients. Leukemia & Lymphoma 44 (2003) 549-553
72. Thiele J, Kvasnicka HM, Facchetti F, Franco V et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 2005; 90: 1128-1132.
73. Thiele J., Hoeppner B., Zankovich R., and Fischer R. Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia)-correlations between clinical and morphological features. Virchows Archiv A Pathology Anatomy Histopathology 415 (1989) 191-202
74. Thiele J, Imbert M, Pierre R, Vardiman JW, et al. Chronic idiopathic myelofibrosis. In Jaffe ES, Harris NL, Stein H& Vardiman JW (eds) WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues., pp 35-38. Lyon: IARC Press, 2001.
75. Kreft A, Buche G, Ghalibafian M, Buhr T et al. The incidence of myelofibrosis in essential thrombocytaemia vera and chronic idiopathic myelofibrosis: a restrospective of evaluation of sequential bone marrow biopsies. Acta Haematol 2005; 113: 137-143.
76. Cervantes F., Barosi G., Demory J.L., Reilly J., et al. Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups. British Journal of Haematology 102 (1998) 684-690
77. Thiele J., Kvasnicka H.M., Schmitt-Graeff A., and Diehl V. Bone marrow histopathology following cytoreductive therapy in chronic idiopathic myelofibrosis. Histopathology 43 (2003) 470-479
78. Thiele J., Rompcik V., Wagner S., and Fischer R. Vascular architecture and collagen type IV in primary myelofibrosis and polycythaemia vera: an immunomorphometric study on trephine biopsies of the bone marrow. British Journal of Haematology 80 (1992) 227-234
79. Kvasnicka H.M., and Thiele J. Bone marrow angiogenesis: methods of quantification and changes evolving in chronic myeloproliferative disorders. Histology and Histopathology 19 (2004) 1245-1260
80. Mesa R.A., Hanson C.A., Rajkumar S.V., Schroeder G., et al. Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia. Blood 96 (2000) 3374-3380
81. Arora B., Ho C.L., Hoyer J.D., Mesa R.A., et al. Bone marrow angiogenesis and its clinical correlates in myelofibrosis with myeloid metaplasia. Haematologica 89 (2004) 1454-1458
82. Van Dyke D., Parker H., Anger H.O., McRae J., et al. Markedly increased bone blood flow in myelofibrosis. Journal of Nuclear Medicine 12 (1971) 506-512
83. Lundberg L.G., Lerner R., Sundelin P., Rogers R., et al. Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity. American Journal of Pathology 157 (2000) 15-19
84. Visani G, Finelli C, Castelli U, Petti MC, et al. Myelofibrosis with myeloid metaplasia: clinical and haematological parameters predicting survival in a series of 133 patients. British Journal of Haematology 1990; 75: 4-9.
85. Rupoli S., Da Lio L., Sisti S., Campanati G., et al. Primary myelofibrosis: a detailed statistical analysis of the clinicopathological variables influencing survival. Annals of Hematology 68 (1994) 205-212
86. Dupriez B., Morel P., Demory J.L., Lai J.L., et al. Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. Blood 88 (1996) 1013-1018
87. Reilly J.T. Idiopathic myelofibrosis: pathogenesis, natural history and management. Blood Reviews 11 (1997) 233-242
88. Kvasnicka H.M., Thiele J., Werden C., Zankovich R., et al. Prognostic factors in idiopathic (primary) osteomyelofibrosis. Cancer 80 (1997) 708-719
89. Kvasnicka H.M., Thiele J., Regn C., Zankovich R., et al. Prognostic impact of apoptosis and proliferation in idiopathic (primary) myelofibrosis. Annals of Hematology 78 (1999) 65-72
90. Thiele J & Kvasnicka HM. 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. Histology and Histopathology 2003; 18: 93-102.
91. Thiele J, Kvasnicka HM, 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.
92. Thiele J & Kvasnicka HM. Chronic myeloproliferative disorders with thrombocythemia: a comparative study of two classification systems (PVSG, WHO) on 839 patients. Annals of Hematology 2003; 82: 148-152.
93. Imbert M, Pierre R, Thiele J, Vardiman JW, et al. Essential thrombocythaemia. In Jaffe ES, Harris NL, Stein H& Vardiman JW (eds) WHO Classification of Tumours: Tumours of Haematopoietic and Lymphoid Tissues., pp 39-41. Lyon: IARC Press, 2001.
94. Florena A.M., Tripodo C., Iannitto E., Porcasi R., et al. Value of bone marrow biopsy in the diagnosis of essential thrombocythemia. Haematologica 89 (2004) 911-919
95. Annaloro C., Lambertenghi Deliliers G., Oriani A., Pozzoli E., et al. Prognostic significance of bone marrow biopsy in essential thrombocythemia. Haematologica 84 (1999) 17-21
96. Thiele J., Kvasnicka H.M., Schmitt-Graeff A., Zankovich R., et al. Follow-up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): a retrospective clinicopathological study of 120 patients. American Journal of Hematology 70 (2002) 283-291
97. Cervantes F., Alvarez-Larran A., Talarn C., Gomez M., et al. Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients. British Journal of Haematology 118 (2002) 786-790
98. Radaelli F., Mazza R., Curioni E., Ciani A., et al. Acute megakaryocytic leukemia in essential thrombocythemia: an unusual evolution?. European Journal of Haematology 69 (2002) 108-111
99. Petrides P.E. Anagrelide: a decade of clinical experience with its use for the treatment of primary thrombocythaemia. Expert Opinion on Pharmacotherapy 5 (2004) 1781-1798
100. Dingli D & Tefferi A. Anagrelide: an update on its mechanisms of action and therapeutic potential. Expert Review of Anticancer Therapy 2004; 4: 533-541.
101. Birgegard G., Bjorkholm M., Kutti J., Larfars G., et al. Adverse effects and benefits of two years of anagrelide treatment for thrombocythemia in chronic myeloproliferative disorders. Haematologica 89 (2004) 520-527
102. Tomer A. Effects of anagrelide on in vivo megakaryocyte proliferation and maturation in essential thrombocythemia. Blood 99 (2002) 1602-1609
103. Thiele J., Kvasnicka H.M., Fuchs N., Brunnbauer K., et al. Anagrelide-induced bone marrow changes during therapy of chronic myeloproliferative disorders with thrombocytosis - an immunohistochemical and morphometric study of sequential trephine biopsies. Haematologica 88 (2003) 1130-1138