Organ Stiffness in the Work-Up of Myelofibrosis and Philadelphia-Negative Chronic Myeloproliferative Neoplasms.

Edoardo Benedetti,Serena Balducci,Federica Ricci,Vittorio Ricchiuto,Claudia Baratè,Gabriele Buda,Riccardo Morganti,Rita Tavarozzi,Sara Galimberti,Lorenzo Iovino,Benedetto Bruno,Emilia Bramanti

doi:10.3390/jcm9072149

Abstract

To define the role of spleen stiffness (SS) and liver stiffness (LS) in myelofibrosis and other Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), we studied, by ultrasonography (US) and elastography (ES), 70 consecutive patients with myelofibrosis (MF) (no.43), essential thrombocythemia (ET) (no.10), and polycythemia vera (PV) (no.17). Overall, the median SS was not different between patients with MF and PV (p = 0.9); however, both MF and PV groups had significantly higher SS than the ET group (p = 0.011 and p = 0.035, respectively) and healthy controls (p < 0.0001 and p = 0.002, respectively). In patients with MF, SS values above 40 kPa were significantly associated with worse progression-free survival (PFS) (p = 0.012; HR = 3.2). SS also correlated with the extension of bone marrow fibrosis (BMF) (p < 0.0001). SS was higher in advanced fibrotic stages MF-2, MF-3 (W.H.O. criteria) than in pre-fibrotic/early fibrotic stages (MF-0, MF-1) (p < 0.0001) and PFS was significantly different in the two cohorts, with values of 63% and 85%, respectively (p = 0.038; HR = 2.61). LS significantly differed between the patient cohort with MF and healthy controls (p = 0.001), but not between the patient cohorts with ET and PV and healthy controls (p = 0.999 and p = 0.101, respectively). We can conclude that organ stiffness adds valuable information to the clinical work-up of MPNs and could be employed to define patients at a higher risk of progression.

Highlights

Philadelphia-negative chronic myeloproliferative neoplasms (Ph-neg myeloproliferative neoplasia (MPN)) include clinical entities, polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), with very different clinical manifestations and prognoses
Shear wave elastography determines the mechanical properties of a tissue by monitoring the speed of shear waves generated by the ultrasound-induced acoustic radiation force
This integrated technology allows a multi-parametric assessment of both liver and splenic stiffness by the same sonographer employed for conventional B-mode and Doppler examinations [21]

Summary

Introduction

Philadelphia-negative chronic myeloproliferative neoplasms (Ph-neg MPNs) include clinical entities, polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), with very different clinical manifestations and prognoses. Ultrasound sonography (US) has been widely used in clinical practice for more than 40 years in several clinical conditions. It lacks quantitative information on tissue elastic properties [10]. In our study, using conventional US and ES with the same sonographer, we concurrently assessed spleen and liver dimensions and their stiffness in patients with MPNs and in healthy volunteers. Our major aims were to investigate whether patient-specific characteristics, such as spleen stiffness (SS) and liver stiffness (LS), correlated with marrow fibrosis and could be predictive of clinical outcomes in MPN subtypes, with an emphasis on PMF

Methods

Results

Conclusion