Longitudinal prospective analysis of organ stiffness and cardiac function in patients with myelofibrosis treated with ruxolitinib type of study: Prospective single-center cohort study.

Abstract

Background: In myeloproliferative neoplasms (MPNs), fibrosis occurs not only in the bone marrow but also in extramedullary organs such as the liver and spleen, reflected by increased tissue stiffness. Patients with MPNs frequently present with echocardiographic signs of cardiac dysfunction, which may be modifiable through targeted therapy.

Objectives: To evaluate changes in organ stiffness and cardiac function in patients with myelofibrosis (MF) treated with ruxolitinib at baseline, 6, and 12 months.

Methods: This prospective, single-center cohort study enrolled 30 MF patients diagnosed according to the current WHO criteria. At each assessment, clinical and laboratory parameters were evaluated, and abdominal ultrasound with shear wave elastography was performed to measure spleen and liver stiffness, alongside echocardiographic evaluation of cardiac function.

Results: The median age of patients was 50 years (range, 21-76). After 6 months of treatment, both liver size (p=0.049) and spleen size (p<0.001) significantly decreased, accompanied by reduced liver and spleen stiffness, while echocardiographic parameters remained unchanged. Significant decreases were also observed in hemoglobin (p=0.017), absolute neutrophil count (p=0.025), platelets (p=0.003), neutrophil-to-lymphocyte ratio (p=0.007), and platelet-to-lymphocyte ratio (p=0.04). Patients reported a notable reduction in symptom burden. At 12 months, organ diameters and stiffness remained stable. Echocardiography demonstrated improved systolic pulmonary artery pressure (sPAP) with a significant difference compared with baseline (p<0.001), while NT-proBNP levels decreased by 50%. Laboratory parameters were largely stable, except for a significant decrease of lactate dehydrogenase. Ruxolitinib was initiated earlier in primary MF, but no significant differences between primary and secondary MF were observed regarding organ stiffness or cardiac findings after 12 months.

Conclusion: Ruxolitinib demonstrated its greatest benefit at 6 months, significantly reducing organ size, stiffness, and symptom burden, followed by cardiovascular improvement and normalization of sPAP by 12 months. Further larger prospective studies with longer follow up are needed for definitive conclusion.