Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders
TLDR
Among the ‘classic’ BCR/ABL-negative chronic myeloproliferative disorders, primary myelofibrosis (PMF) is associated with a substantial life-expectancy reduction and the importance of higher leukocyte counts in thrombosis development has been recently pointed out in ET and PV, where a role for mutated JAK2 allele burden has been noted.Abstract:
Among the 'classic' BCR/ABL-negative chronic myeloproliferative disorders, primary myelofibrosis (PMF) is associated with a substantial life-expectancy reduction. In this disease, initial haemoglobin level is the most important prognostic factor, whereas age, constitutional symptoms, low or high leukocyte counts, blood blast cells and cytogenetic abnormalities are also of value. Several prognostic systems have been proposed to identify subgroups of patients with a different risk, which is especially important in younger individuals, who may benefit from therapies with curative potential. Essential thrombocythaemia (ET) affects the patients' quality of life more than the survival, due to the high occurrence of thrombosis, whereas polycythaemia vera (PV) has a substantial morbidity derived from thrombosis but also a certain reduction in life expectancy. Therefore, in the latter disorders, prognostic studies have focused primarily on prediction of the thrombosis, with age and a previous history of thrombosis being the main prognostic factors of such complication. The importance of higher leukocyte counts in thrombosis development has been recently pointed out in ET and PV, where a role for mutated JAK2 allele burden has also been noted. With regard to PMF, the possible association of the mutation with shorter survival and higher acute transformation rate is currently being evaluated.read more
Citations
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Journal ArticleDOI
Safety and Efficacy of INCB018424, a JAK1 and JAK2 Inhibitor, in Myelofibrosis
Srdan Verstovsek,Hagop M. Kantarjian,Ruben A. Mesa,Animesh Pardanani,Jorge Cortes-Franco,Deborah A. Thomas,Zeev Estrov,Jordan S. Fridman,Edward C Bradley,Susan Erickson-Viitanen,Kris Vaddi,Richard S. Levy,Ayalew Tefferi +12 more
TL;DR: INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed, and clinical benefits were associated with a marked diminution of levels of circulating inflammatory cytokines that are commonly elevated in myel ofibrosis.
Journal ArticleDOI
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.
Francesco Passamonti,Elisa Rumi,Daniela Pietra,Chiara Elena,Emanuela Boveri,Luca Arcaini,Elisa Roncoroni,Cesare Astori,Michele Merli,Sabrina Boggi,Cristiana Pascutto,Mario Lazzarino,Mario Cazzola +12 more
TL;DR: A JAK2 (V617F) allele burden >50% represents a risk factor for progression to MF in PV and did not affect thrombosis, MF, leukemia or survival.
Journal ArticleDOI
Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients
Francesco Passamonti,Elisa Rumi,Luca Arcaini,Emanuela Boveri,Chiara Elena,Daniela Pietra,Sabrina Boggi,Cesare Astori,Paolo Bernasconi,Marzia Varettoni,Ercole Brusamolino,Cristiana Pascutto,Mario Lazzarino +12 more
TL;DR: The findings from this study on a large series of patients treated according to current clinical practice provide reassurance that essential thrombocythemia is an indolent disorder and affected patients have a long survival.
Journal ArticleDOI
EZH2 mutational status predicts poor survival in myelofibrosis
Paola Guglielmelli,Flavia Biamonte,Joannah Score,Joannah Score,Claire Hidalgo-Curtis,Claire Hidalgo-Curtis,Francisco Cervantes,Margherita Maffioli,Tiziana Fanelli,Thomas Ernst,Nils Winkelman,Amy V. Jones,Amy V. Jones,Katerina Zoi,Andreas Reiter,Andrew S Duncombe,Laura Villani,Alberto Bosi,Giovanni Barosi,Nicholas C.P. Cross,Nicholas C.P. Cross,Alessandro M. Vannucchi +21 more
TL;DR: EZH2 mutations are independently associated with shorter survival in patients with PMF and in multivariate analysis, survival of PMF patients was predicted by IPSS high-risk category, a < 25% JAK2V617F allele burden, and EZh2 mutation status.
Journal ArticleDOI
A prognostic model to predict survival in 867 World Health Organization-defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment.
Francesco Passamonti,Jürgen Thiele,François Girodon,Elisa Rumi,Alessandra Carobbio,Heinz Gisslinger,Hans Michael Kvasnicka,Marco Ruggeri,Maria Luigia Randi,Naseema Gangat,Alessandro M. Vannucchi,Andrea Gianatti,Bettina Gisslinger,Leonhard Müllauer,Francesco Rodeghiero,Emanuele S.G. d'Amore,Irene Bertozzi,Curtis A. Hanson,Emanuela Boveri,Filippo Marino,Margherita Maffioli,Domenica Caramazza,Elisabetta Antonioli,Valentina Carrai,Veronika Buxhofer-Ausch,Cristiana Pascutto,Mario Cazzola,Tiziano Barbui,Ayalew Tefferi +28 more
TL;DR: IPSET, based on age ≥ 60 years, leukocyte count ≥ 11 × 10(9)/L, and history of thrombosis allows prognostic assessment of WHO-defined ET and the validation process makes IPSET applicable in all patients phenotypically appearing as ET.
References
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A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders
Robert Kralovics,Francesco Passamonti,Andreas Buser,Soon Siong Teo,Ralph Tiedt,Jakob Passweg,André Tichelli,Mario Cazzola,Radek C. Skoda +8 more
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Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.
Ross L. Levine,Ross L. Levine,Martha Wadleigh,Jan Cools,Benjamin L. Ebert,Benjamin L. Ebert,Gerlinde Wernig,Brian J. P. Huntly,Titus J. Boggon,Iwona Wlodarska,Jennifer J. Clark,Sandra A. Moore,Jennifer Adelsperger,Sumin Koo,Jeffrey C. Lee,Stacey Gabriel,Thomas Mercher,Alan D. D'Andrea,Stefan Fröhling,Konstanze Döhner,Peter Marynen,Peter Vandenberghe,Ruben A. Mesa,Ayalew Tefferi,James D. Griffin,Michael J. Eck,William R. Sellers,William R. Sellers,Matthew Meyerson,Matthew Meyerson,Todd R. Golub,Todd R. Golub,Todd R. Golub,Stephanie J. Lee,D. Gary Gilliland,D. Gary Gilliland,D. Gary Gilliland +36 more
TL;DR: High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations.
Journal ArticleDOI
The World Health Organization (WHO) classification of the myeloid neoplasms.
TL;DR: The purpose of this communication is to outline briefly the WHO classification of malignant myeloid diseases, to draw attention to major differences between it and antecedent classification schemes, and to provide the rationale for those differences.
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