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4071 Clinical and Biological Features in Patients with Ph-Negative Chronic Myeloproliferative Neoplasm Showing Different Molecular Pattern. Comparative Study in 596 Patients of the Registro Italiano Trombocitemie (RIT)

Myeloproliferative Syndromes: Clinical
Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Luigi Gugliotta, MD1, Alessandra Iurlo, MD, PhD2*, Gabriele Gugliotta, PhD3*, Alessia Tieghi, MD4*, Giorgina Specchia5, Gianluca Gaidano6*, Anna Candoni, MD7*, Maria Luigia Randi, MD8*, Potito Rosario Scalzulli, MD9*, Alfredo Dragani, MD10*, Vincenzo Martinelli, MD11*, Giuseppe Tagariello, MD12, Elisabetta Antonioli, MD13*, Anna Marina Liberati, MD14, Raffaele Palmieri, MD15*, Maria Langella, MD16*, Angela Rago, MD17*, Rossella R Cacciola, MD18, Ivana Pierri, MD19*, Alessandra Ricco, MD20*, Daniele Cattaneo, MD21*, Umberto Santoro, MD22*, Serena Rupoli, MD23*, Cristina Santoro, MD24*, Lucia Mastrullo, MD25*, Bruno Martino, MD26*, Maria Gabriella Mazzucconi, MD27*, Nicola Vianelli, MD28*, Valerio De Stefano, MD29*, Francesco Passamonti30* and Alessandro M. Vannucchi, MD, PhD31

1Hematology/Oncology Dept, Bologna University, Istituto Seragnoli, S Orsola Malpighi University Hospital, Bologna, Italy
2Division of Hematology, IRCCS Maggiore Policlinico Hospital Foundation, Milano, Italy
3Institute of Hematology, University of Bologna and S.Orsola - Malpighi Hospital, Bologna, Italy
4Hematology Dept., A.O. Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy
5Hematology - Dept. of Emergency and Organ Transplantation, University of Bari, Bari, Italy
6Division of Haematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy
7Hematology, Santa Maria della Misericordia University Hospital, Udine, Italy
8Internal Medicine, University Hospital, Padova, Italy
9Hematology and BMT Unit, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
10Hematology Dept, Santo Spirito Hospital, Pescara, Italy
11Hematology Dept., University Federico II, Napoli, Italy
12Hematology, Transfusion Service, Hemophilia and Regional Blood Disease Centre, Castelfranco Veneto, Italy
13Hematology Dept., AOU Careggi University Hospital, Firenze, Italy
14Hematology, Ospedale Perugia, Perugia, Italy
15Hematology Dept., S. Giuseppe Moscati Hospital, Avellino, Italy
16Hematology Unit, Civic Hospital, Nocera Inferiore, Italy
17UOC of Hematology, University, Latina, Italy
18Biomedical Science, Section of Hematology, Catania, Italy
19Hematology Clinic, IRCSS AOU S.Martino-IST, University of Genova, Genova, Italy
20Department of Hematology, University of Bari, Bari, Italy
21Department of Hematology, IRCCS Maggiore Policlinico Hospital Foundation, Milan, Italy
22Statistical Sciences Dept., University of Bologna, Bologna, Italy
23Haematology Clinic, Ospedali Riuniti di Ancona, Ancona, Italy
24University of Rome “Sapienza”, Department of Cellular Biotechnologies and Hematology, Rome, Italy
25Hematology Dept., S. Gennaro/S. Giovanni Bosco Hospitals, Napoli, Italy
26Hamatology Dept., Ospedali Riuniti Bianchi Melacrino Morelli, Reggio Calabria, Italy
27Centro Regionale di Riferimento per l’Emofilia e Sindromi Correlate, Universitŕ Sapienza, Policlinico Umberto I, Rome, Italy
28Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy
29Hematology, Catholic University, Rome, Italy
30Ospedale di Circolo e Fondazione Macchi, Varese, Italy
31Department of Hematology, Universitá degli Studi di Firenze, Firenze, Italy

Background. In patients with Ph-negative chronic myeloproliferative neoplasm (MPN) the molecular pattern, beside other characteristics at diagnosis, has been related to the disease prognosis.

Aim. To compare clinical and biological features at diagnosis and during the follow-up in gender/age-matched MPN patients showing different molecular pattern.

Material and methods. The Registro Italiano Trombocitemie (RIT) is a web-based registry that includes thrombocythemic MPN patients diagnosed according to PVSG or WHO criteria, registered after 2005, and then prospectically followed. The JAK2 V617F mutation (JAK2+) was reported in 941 (58.4%) out of 1610 tested patients. On the basis of subsequent tests, performed in part of the JAK2 WT (JAK2-) subjects, 103 patients were  JAK2-/CALR+ (CALR+), 14 patients were JAK2-/CALR-/MPL+ (MPL+), and 46 were JAK2-/CALR-/MPL- (3NEG).

The 103 CALR+ patients were compared with 309 (103 x 3) JAK2+ patients matched for gender, age, and revised diagnosis (WHO 2008 criteria). A similar comparison was done between 46 3NEG patients and other 138 (46 x 3) JAK2+ matched patients.

Results. CALR+ and matched JAK2+ patients had, as expected, the same gender distribution (males 41%), the same median age (51 years), and no significant difference  (p 0.42) in the WHO diagnosis distribution.

CALR+ patients, as compared with JAK2+ patients, showed at diagnosis: higher median platelet (PLT) count (839 vs 718 x109/L, p<0.001); lower median white blood cell (WBC) count (7.3 vs 8.9 x109/L, p<0.001); lower median hemoglobin (Hb, 14.2 vs 14.8 g/dL in males, p 0.01; 12.9 vs 14.0 g/dL in females, p<0.001); lower median hematocrit (HCT, 42.4 vs 45.0 %, p 0.002 in males; 38.7 vs 42.2 in females, p<0.001); lower rate of low (<5) serum erythropoietin (0 vs 32%, p 0.003); lower rate of prior thrombosis (PrTh, 5/103, 4.9% vs 60/309, 19.4%, p<0.001), observed for both arterial and venous PrTh; lower rate of high/intermediate thrombotic risk (IPSET, 37% vs 55%, p 0.003).

CARL+ and JAK2+ patients had the same rate of antiplatelet and cytoreductive treatment (96% vs 96%, and 86% vs 84%, respectively). During the follow-up the incidence of thrombotic and hemorrhagic events was not significantly different (1.3 vs 1.1/100 pt-years, and 1.0 vs 0.6/100 pt-years, respectively). Moreover, no significant difference was observed in the incidence of evolution to overt primary myelofibrosis (PMF, 0.76 vs 0.61/100 pt-years), polycythemia vera (PV, 0 vs 0.24/100 pt-years), and AL/MDS (0.08 vs 0.10/100 pt-years).

Finally, the same  overall survival was found after 5, 10. 15, and 20 years (99, 97, 94, 93%, respectively).

3NEG patients, as compared with JAK2+ matched patients, showed at diagnosis: lower median WBC count (7.9 vs 10.9 x 109/L, p 0.03); lower Hb and/or HCT level (p 0.006); lower rate of splenomegaly (7% vs 28%, p 0.003); lower rate of symptoms (35% vs 51%, p 0.049). No significant difference  was found in: median PLT count (700 vs  720 x 109/L, p 0.61); PrTh (7% vs 16%, p 0.11); prior hemorrhage (4.7% vs 7.5%, p 0.52); high/intermediate thrombotic risk (IPSET, 36 vs 48%, p 0.37). Moreover, no significant difference was observed during the follow-up in: antiplatelet and cytoreductive treatment; thrombosis and hemorrhage rate; PMF, PV, and AL/MDS evolution; overall survival.

Conclusion. CALR+ patients, as compared with JAK2+ matched patients, although showed a lower thrombotic risk (lower WBC and HCT levels, lower PrTh rate), received the same antiplatelet and cytoreductive treatment, had the same incidence of adverse events during the follow-up (vascular complications and disease evolution/transformation), and had the same overall survival.

3NEG patients, as compared with JAK2+ matched patients, showed results similar to those observed by comparing CALR+ and JAK2+ matched patients.

To better define the role of the precise definition of molecular pattern in Ph-MPN patients, new prospective controlled studies seem necessary.

Disclosures: De Stefano: Janssen Cilag: Research Funding ; Roche: Research Funding ; Novartis: Research Funding , Speakers Bureau ; Amgen: Speakers Bureau ; Bruno Farmaceutici: Research Funding ; Celgene: Speakers Bureau ; GlaxoSmithKline: Speakers Bureau ; Shire: Speakers Bureau . Passamonti: Novartis: Consultancy , Honoraria , Speakers Bureau .

*signifies non-member of ASH