Leukocytosis at Diagnosis in Patients with Essential Thrombocythemia Is a Risk Factor for Transformation into Myelofibrosis

Irene Bertozzi, Fabiana Tezza, Emanuela Bonamigo, Fabrizio Fabris, Maria Luigia Randi

Dept of Medical and Surgical Sciences, University of Padua, Italy.

DOI: 10.4236/ojbd.2012.23009                

Abstract

Myelofibrosis (MF) represents the major long-term complication of essential thrombocythemia (ET). There is evidence that leukocytosis at diagnosis is associated with poorer survival in patients with ET. In this study, we retrospectively evaluated 143 patients with ET, diagnosed in agreement with WHO criteria, followed in a single centre over >10 years. Nine of them transformed into MF (post-essential thrombocythemia-myelofibrosis PET-MF). We compared PET-MF data at diagnosis with that of the remaining 134 patients (ET-1) and with a selected sub-group of ET-1 (ET-2, 19 pats) sex, age and follow-up duration matched to PET-MF. The PET-MF evolution rate was 4.6 per 1000 person-years; white blood cells count (WBC) count, haemoglobin levels and hematocrit were higher in PET-MF than in ET-1 (P = 0.01) while only WBC was higher than in ET-2 (P = 0.01). With multivariate analysis, only WBC count retained its signifi-cance. Our study highlights the prognostic relevance of leukocytosis on myelofibrotic transformation of ET.

Keywords

Essential Thrombocythemia; Leukocytosis; Post-Thrombocythemia Myelofibrosis; Myeloproliferative Neoplasms

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	[1] C. Rozman, E. Feliu, M. Giralt, D. Rubio and M. T. Cortés, “Life Expectancy of Patients with Chronic Nonleukemic Myeloproliferative Disorders,” Cancer, Vol. 67, No. 10, 1991, pp. 2656-2663. doi:10.1002/1097-0142(19910515)67:10<2658::AID-CNCR2820671042>3.0.CO;2-C
[2]	F. Girodon, F. Dutrillaux, J. Broséus, M. Mounier, V. Goussot, P. Bardonnaud, et al., “Leukocytosis Is Associated with Poor Survival But Not with Increased Risk of Thrombosis in Essential Thrombocythemia: A Population-Based Study of 311 Patients,” Leukemia, Vol. 24, No. 4, 2010, pp. 900-903. doi:10.1038/leu.2010.5
[3]	N. Gangat, J. Strand, C.-Y. Li, W. T. Wu, A. Pardanani and A. Tefferi, “Leukocytosis in Polycythemia Vera Predicts Both Inferior Survival and Leukemic Transformation,” British Journal of Haematology, Vol. 138, No. 3, 2007, pp. 354-358. doi:10.1111/j.1365-2141.2007.06674.x
[4]	F. Palandri, L. Catani, N. Testoni, E. Ottaviani, N. Polverelli, M. Fiacchini, et al., “Long-Term Follow-Up of 386 Consecutive Patients with Essential Thrombocythemia: Safety of Cytoreductive Therapy,” American Journal of Hematology, Vol. 84, No. 4, 2009, pp. 215-220. doi:10.1002/ajh.21360
[5]	N. Gangat, A. P. Wolanskyj, R. F. McClure, C.-Y. Li, S. Schwager, W. Wu and A. Tefferi, “Risk Stratification for Survival and Leukemic Transformation in Essential Thrombocythemia: A Single Institutional Study of 605 Patients,” Leukemia, Vol. 21, No. 2, 2007, pp. 270-276. doi:10.1038/sj.leu.2404500
[6]	J. J. Kiladjian, C. Gardin, M. Renoux, F. Bruno and J. F. Bernard, “Long-Term Outcomes of Polycythemia Vera Patients Treated with Pipobroman as Initial Therapy,” The Hematology Journal, Vol. 4, 2003, pp. 198-207. doi:10.1038/sj.thj.6200250
[7]	G. Finazzi, V. Caruso, R. Marchioli, G. Capnist, T. Chisesi, C. Finelli, et al., “Acute Leukemia in Polycythemia Vera: An Analysis of 1638 Patients Enrolled in a Prospective Observational Study,” Blood, Vol. 105, No. 7, 2005, pp. 2664-2670. doi:10.1182/blood-2004-09-3426
[8]	P. Guglielmelli, G. Barosi, L. Pieri, E. Antonioli, A. Bosi and A. M. Vannucchi, “JAK2V617F Mutational Status and Allele Burden Have Little Influence on Clinical Phenotype and Prognosis in Patients with Post-Polycythemia Vera and Post-Essential Thrombocythemia Myelofibrosis,” Haematologica, Vol. 94, No. 1, 2009, pp. 144-146. doi:10.3324/haematol.13721
[9]	G. Barosi, G. Bergamaschi, M. Marchetti, A. M. Vannucchi, P. Guglielmelli, E. Antonioli, et al., “JAK2V617F Mutational Status Predicts Progression to Large Splenomegaly and Leukemic Transformation in Primary Myelofibrosis,” Blood, Vol. 110, No. 12, 2007, pp. 4030-4036. doi:10.1182/blood-2007-07-099184
[10]	F. Passamonti, E. Rumi, D. Pietra, C. Elena, E. Boveri, E. Roncoroni, et al., “A Prospective Study of 338 Patients with Polycythemia Vera: The Impact of JAK2(V617F) Allele Burden and Leukocytosis on Fibrotic or Leukemic Disease Transformation and Vascular Complications,” Leukemia, Vol. 24, No. 9, 2010, pp. 1574-1579. doi:10.1038/leu.2010.148
[11]	J. W. Vardiman, J. Thiele, D. A. Arber, R. D. Brunning, M. J. Borowitz, A. Porwit, et al., “The 2008 Revision of the WHO Classification of Myeloid Neoplasms and Acute Leukemia: Rationale and Important Changes,” Blood, Vol. 114, No. 5, 2009, pp. 937-951. doi:10.1182/blood-2009-03-209262
[12]	G. Barosi, R. Mesa, J. Thiele, F. Cervantes, P. J. Campbell, S. Verstovsek, et al., “Proposed Criteria for the Diagnosis of Post-Polycythemia Vera and Post-Essential Thrombocythemia Myelofibrosis: A Consensus Statement from the International Working Group for Myelofibrosis Research and Treatment,” Leukemia, Vol. 22, No. 2, 2008, pp. 437-438. doi:10.1038/sj.leu.2404914
[13]	M. A. Elliott, S.-Y. Yoon, P. Kao, C.-Y. Li and A. Tefferi, “Simultaneous Measurement of Serum Thrombopoietin and Expression of Megakaryocyte c-Mpl with Clinical and Laboratory Correlates for Myelofibrosis with Myeloid Metaplasia,” European Journal of Haematology, Vol. 68, No. 3, 2002, pp. 175-179. doi:10.1034/j.1600-0609.2002.01534.x
[14]	S. Murphy, P. Peterson, H. Iland and J. Laszlo, “Experience of the Polycythemia Vera Study Group with Essential Thrombocythemia: A Final Report on Diagnostic Criteria, Survival and Leukemic Transformation by Treatment,” Seminars in Hematology, Vol. 34, No. 1, 1997, pp. 29-39.
[15]	F. Cervantes, A. Alvarez-Larrán, C. Talarn, M. Gómez and E. Montessart, “Myelofibrosis with Myeloid Metaplasia Following Essential Thrombocythemia: Actuarial Probability, Presenting Characteristics and Evolution in a Series of 195 Patients,” British Journal of Haematology, Vol. 118, No. 3, 2002, pp. 786-790. doi:10.1046/j.1365-2141.2002.03688.x
[16]	F. Passamonti, E. Rumi, E. Pungolino, L. Malabarba, P. Bertazzoni, M. Valentini, et al., “Life Expectancy and Prognostic Factors for Survival in Patients with Polycythemia Vera and Essential Thrombocythemia,” The American Journal of Medicine, Vol. 117, No. 10, 2004, pp. 755-761. doi:10.1016/j.amjmed.2004.06.032
[17]	R. Landolfi, L. Di Gennaro, T. Barbui, V. De Stefano, G. Finazzi, R. M. Marfisi, et al., “Leukocytosis as a Major Thrombotic Risk Factor in Patients with Polycythemia Vera,” Blood, Vol. 109, No. 6, 2007, pp. 2446-2452. doi:10.1182/blood-2006-08-042515
[18]	A. Carobbio, E. Antonioli, P. Guglielmelli, A. M. Vannucchi, F. Delaini, V. Guerini, et al., “Leukocytosis and Risk Stratification Assessment in Essential Thrombocythemia,” Journal of Clinical Oncology, Vol. 26, No. 16, 2008, pp. 2732-2736. doi:10.1200/JCO.2007.15.3569
[19]	F. Passamonti, E. Rumi, L. Arcaini, E. Boveri, C. Elena, D. Pietra, et al., “Prognostic Factors for Thrombosis, Myelofibrosis and Leukemia in Essential Thrombocythemia: A Study of 605 Patients,” Haematologica, Vol. 93, No. 11, 2008, pp. 1645-1651. doi:10.3324/haematol.13346
[20]	A. Tefferi, N. Gangat, A. P. Wolanskyj, S. Schwager, A. Pardanani, T. L. Lasho, et al., “20+ yr without Leukemia or Fibrotic Transformation in Essential Thrombocythemia or Polycythemia Vera: Predicts at Diagnosis,” European Journal of Haematology, Vol. 80, No. 5, 2008, pp. 386390. doi:10.1111/j.1600-0609.2008.01038.x
[21]	T. Barbui, J. Thiele, F. Passamonti, E. Rumi, E. Boveri, M. Ruggeri, et al., “Survival and Disease Progression in Essential Thrombocythemia Are Significantly Influenced by Accurate Morphologic Diagnosis: An International Study,” Journal of Clinical Oncology, Vol. 29, No. 23, 2011, pp. 3179-3184. doi:10.1200/JCO.2010.34.5298
[22]	A. P. Wolanskyj, S. M. Schwager, R. F. McClure, D. R. Larson and A. Tefferi, “Essential Thrombocythemia beyond the First Decade: Life Expectancy, Long-Term Complication Rates, and Prognostic Factors,” Mayo Clinic Proceedings, Vol. 81, No. 2, 2006, pp. 159-166. doi:10.4065/81.2.159