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Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.

Published version
Peer-reviewed

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Authors

Sirinukunwattana, Korsuk 
Grindstaff, Gillian 
Stolz, Bernadette J 

Abstract

The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n = 107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.

Description

Keywords

Humans, Primary Myelofibrosis, Polycythemia Vera, Myeloproliferative Disorders, Bone Marrow, Thrombocythemia, Essential, Fibrosis

Journal Title

Leukemia

Conference Name

Journal ISSN

0887-6924
1476-5551

Volume Title

37

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research UK (CRUK) (C68644/A30721)