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

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

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.

Keywords: fibrosis; myeloproliferative neoplasms; spleen; splenic stiffness; ultrasound.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Spleen dimensions in a healthy control: splenic longitudinal diameter (SLD) (10.35 cm) (A), cross-sectional area (CSA) (41.62 cm2) (B), and splenic stiffness (SS) (17.6 kPA, IQR/M 14) (C). Spleen dimensions before and 1 year after treatment with Ruxolitinib in a patient with myelofibrosis: SLD (17.61 cm) (D), CSA (107 cm2) (E), and SS (41.7 kPA, IQR/M 19) (F); and SLD (16.85 cm) (G), CSA (93.64 cm2) (H), and SS (28 kPA, IQR/M 21) (I), respectively.
Figure 2
Figure 2
Comparisons of spleen stiffness (also see text): (A) Healthy controls vs. patients with myeloproliferative neoplasms (p < 0.0001); (B) healthy controls vs. myelofibrosis (MF) (p < 0.0001), healthy controls vs. polycythemia vera (PV) (p = 0.002), essential thrombocytopenia (ET) vs. MF (p = 0.014), and ET vs. PV (p = 0.027).
Figure 3
Figure 3
(A) Correlations of spleen stiffness with the Dynamic International Prognostic Scoring System (DIPSS). A trend between the low-risk and the intermediate (Int-1) group was reported (p = 0.059), while no difference was seen between the Int-1 and Int-2 (p = 0.541) groups, and the Int-1 and Int-2 with the high-risk group (p = 0.611 and p = 0.916). (B) Liver stiffness 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). Multiple comparisons did not show differences in liver stiffness between the different MPN categories (ET vs. MF, p = 0.440; ET vs. PV, p = 0.999; and MF vs. PV, p = 0.999).
Figure 4
Figure 4
Spleen stiffness (SS) and bone marrow fibrosis (BMF) and progression-free survival (PFS) (Cox regression model) in patients with myelofibrosis. (A) PFS in patients with SS lower than the median value (40 kPa) (dotted line) vs. those with higher values (solid line) (p = 0.089; Hazard Ratio (HR) = 1.939 (range 0.891-4.071)). (B) PFS in patients with BMF grade MF-0, MF-1 (solid line) vs. those with BMF MF-2, MF-3 (dotted line). F0, F1, F2, and F3 in the legend represent MF-0, MF-1, MF-2, and MF-3, respectively.

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