The evolution and clinical relevance of prognostic classification systems in myelofibrosis

Abstract

Condensed abstract: This article traces the evolution of prognostic criteria and scoring systems for myelofibrosis, both primary and post-PV/ET, from early CBC-based systems to the current genomic era. Prognostic factors for not only survival, but also thrombosis and leukemic transformation, are discussed, and the clinical utility and drawbacks/pitfalls of the current and proposed systems examined.Funding: This research is supported in part by the MD Anderson Cancer Center Support Grant CA016672 from the National Institutes of Health.Conflict of interest statement: Neither PB nor SV have any conflicts of interest relevant to this manuscript. Page 1 of 37 CancerThis is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version record. Please cite this article as doi:10.1002/cncr.29842.This article is protected by copyright. All rights reserved. Accepted Article 2 AbstractPrimary myelofibrosis, the most aggressive of the classic Philadelphia-chromosome negative myeloproliferative neoplasms (MPNs), is a clonal disorder characterized by often debilitating constitutional symptoms and splenomegaly, bone marrow fibrosis and resultant cytopenias, extramedullary hematopoiesis, risk of leukemic transformation and shortened survival. Postpolycythemia vera and post-essential thrombocythemia myelofibrosis represent similar entities, although some differences are being recognized. Attempts to classify patients with myelofibrosis into prognostic categories have been made since the late eighties, and these scoring systems continue to evolve as new information becomes available. Over the last decade, the molecular pathogenesis of the MPNs has been considerably elucidated, and the JAK1/2 inhibitor ruxolitinib is the first drug specifically approved by the United States Food and Drug Administration to treat patients with intermediate and high risk myelofibrosis. In this article, we review the evolution of prognostic criteria in myelofibrosis, emphasizing the major systems widely in use today, as well as recently described, novel systems that incorporate emerging data on somatic mutations. Risk factors for thrombosis and conversion to MPN blast phase are also covered. Finally, the practical utility of the current prognostic classification systems in terms of clinical decision-making is discussed, particularly in the context of some of their inherent weaknesses.

3q26.2/EVI1 rearrangement is associated with poor prognosis in classical Philadelphia chromosome-negative myeloproliferative neoplasms

“…In contrast, DIPSS and DIPSS-plus can be used at any given time point during the disease course of myelofibrosis. 5,18,30 The actual overall survival after the emergence of 3q26.2 rearrangement in our study is markedly shorter than the expected overall survival predicted by DIPSS. This indicates that the DIPSS score underestimates the poor prognosis in these patients.…”

Ruxolitinib is effective in patients with intermediate-1 risk myelofibrosis: a summary of recent evidence

“…Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) associated with progressive bone marrow fibrosis and extramedullary hematopoiesis. [ 1 , 2 ] MF may develop as primary MF (PMF) or evolve from polycythemia vera (PV) or essential thrombocythemia (ET) through myelofibrotic disease transformation. [ 3 , 4 ] MF pathogenesis is characterized by dysregulation of JAK-STAT signaling.…”

“…The different prognostic scoring systems developed in recent years reflect a gradual evolution in the understanding of factors that influence prognosis in MF. [ 2 ]…”

Discrepancies of applying primary myelofibrosis prognostic scores for patients with post polycythemia vera/essential thrombocytosis myelofibrosis

“…The risk group was then assigned per published guidelines: low-risk (0 adverse points), intermediate-1 risk (1 adverse point), intermediate-2 risk (2-3 adverse points) and high-risk (4-6 adverse points). In the same patient cohort, and during the same time interval, post-PV risk scores were calculated at time of last follow up: hemoglobin level less than 10 g/dL (1 point), platelet count less than 100x10 9 /L (1 point), and/or leukocyte count more than 30x10 9 /L (1 point). The risk score was then assigned: low-risk (0 adverse points), intermediate-1 risk (1 adverse point), and intermediate-2 risk (2 adverse points), and high-risk (3 adverse points) ( Table 2).…”