Prognostic impact of bone marrow fibrosis in primary myelofibrosis. A study of the AGIMM group on 490 patients.
The prognostic significance of bone marrow (BM) fibrosis grade in patients with primary myelofibrosis (PMF) is still debated. A fibrosis grade greater than 1 was shown to associate with higher risk of death, and addition of fibrosis grade to IPSS score resulted in a more accurate prediction of survival. The aim of this study was to analyze the prognostic impact of BM fibrosis in 490 patients with PMF, evaluated at diagnosis, molecularly annotated and with extensive follow-up information. We found that fibrosis grade 2 and greater on a 0-3 scale was associated with clinical characteristics indicative of a more advanced disease, such as anemia, leukopenia, thrombocytopenia, constitutional symptoms, larger splenomegaly and a higher IPSS risk category. Patients with higher grade of fibrosis were also more likely to have additional somatic mutations in ASXL1 and EZH2, that are prognostically adverse. Median survival was significantly reduced in patients with grade 2 and 3 fibrosis as compared with grade 1; this effect was maintained when analysis was restricted to younger patients. In multivariate analysis, fibrosis grade independently predicted for survival regardless of IPSS variables and mutational status; the adverse impact of fibrosis was noticeable especially in lower IPSS risk categories. Overall, results indicate that higher grades of fibrosis correlate with unique clinical and molecular aspects and represent an independent adverse variable in patients with PMF; these observations deserve confirmation in prospectively designed series of patients. Am. J. Hematol. 91:918-922, 2016. © 2016 Wiley Periodicals, Inc.
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, CRIMM-Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
Paola
P
Guglielmelli
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, CRIMM-Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
Giada
G
Rotunno
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, CRIMM-Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
Annalisa
A
Pacilli
Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Elisa
E
Rumi
Center for the Study of Myelofibrosis, Research Lab of Biotechnology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
Vittorio
V
Rosti
Hematology and BMT Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
Federica
F
Delaini
Ospedale Di Circolo, Fondazione Macchi Università Degli Studi Dell'Insubria, Varese Viale Borri 57, Varese, Italia.
Margherita
M
Maffioli
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, CRIMM-Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.|University of Siena, Italy.
Tiziana
T
Fanelli
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, CRIMM-Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
Alessandro
A
Pancrazzi
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, CRIMM-Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
Lisa
L
Pieri
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, CRIMM-Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
Rajmonda
R
Fjerza
Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Daniela
D
Pietra
Department of Clinical and Biological Sciences University of Turin, San Luigi Hospital Turin, Italy.
Daniela
D
Cilloni
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, CRIMM-Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
Emanuela
E
Sant'Antonio
Hematology and BMT Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
Silvia
S
Salmoiraghi
Ospedale Di Circolo, Fondazione Macchi Università Degli Studi Dell'Insubria, Varese Viale Borri 57, Varese, Italia.
Francesco
F
Passamonti
Hematology and BMT Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.
Alessandro
A
Rambaldi
Center for the Study of Myelofibrosis, Research Lab of Biotechnology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
Giovanni
G
Barosi
Research Foundation, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Tiziano
T
Barbui
Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Mario
M
Cazzola
Department of Experimental and Clinical Medicine and DENOTHE Excellence Center, CRIMM-Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
Alessandro M
AM
Vannucchi
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology; D001772:Blood Cell Count; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055728:Primary Myelofibrosis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D013163:Splenomegaly / Q000209:etiology; D013921:Thrombocytopenia / Q000209:etiology; D055815:Young Adult
D006454:Hemoglobins