Elsevier

Leukemia Research

Volume 59, August 2017, Pages 110-116
Leukemia Research

Research paper
Patients with post-essential thrombocythemia and post-polycythemia vera differ from patients with primary myelofibrosis

https://doi.org/10.1016/j.leukres.2017.06.001Get rights and content

Highlights

  • Retrospective comparison of 1099 patients with primary and PET/PPV-MF myelofibrosis.

  • Patients with PET-MF have longer overall survival than those with PPV-MF and PMF.

  • Current prognostic scoring systems are not valid for prognostication of PET/PPV-MF.

  • More accurate prognostic factors for PET/PPV-MF are needed.

Abstract

Prognostic scoring systems for primary myelofibrosis (PMF) are not accurate in patients with post-essential thrombocythemia and post-polycythemia vera myelofibrosis (PET-MF; PPV-MF). Given the paucity of data describing the clinical characteristics, disease course and outcomes of these patients, we sought to describe and compare the clinical characteristics and outcomes of 755 patients with PMF, 181 with PPV-MF, and 163 with PET-MF referred to our institution between 1984 and 2013. The median follow-up was 31 months, and 56% (n = 616) patients had died. Over an observation period of 3502 person-years, 11% of patients had progression to AML, with similar rates among groups. The proportion of patients with transfusion dependency (higher in PMF), leukocytosis and systemic symptoms (higher in PPV-MF), and thrombocytopenia (higher in PMF, PPV-MF) differed among groups. Median overall survival (OS) was longest in PET-MF patients (73 mo vs 45 mo (PMF) vs 48 mo (PPV-MF), p < 0.001). Stratification of OS by DIPSS was only discriminatory in patients with PMF, and it failed to distinguish higher risk patients with PPV/PET-MF. In multivariate analysis, predictors of inferior OS were higher age, anemia, systemic symptoms, thrombocytopenia, and high peripheral blasts in PMF; age, anemia, and systemic symptoms for PPV-MF; and anemia, peripheral blasts and thrombocytopenia in PET-MF. Although the clinical characteristics of PPV/PET-MF patients are not substantially different from those with PMF, their outcomes differ and prognostic scoring systems for PET/PPV-MF should be improved.

Introduction

The classical Ph negative chronic myeloproliferative neoplasms (MPN) polycythemia vera (PV) and essential thrombocythemia (ET), though considered relatively benign, share a propensity to progress toward a fibrotic stage (so-called post polycythemia vera myelofibrosis, [PPV-MF] and post essential thrombocythemia myelofibrosis [PET-MF]). PPV- and PET-MF, like primary MF (PMF), are characterized by typical MF features: decreased peripheral blood counts owing to accumulation of reticulin/collagen fibrosis and subsequent bone marrow failure; extramedullary hematopoiesis often accompanied by significant splenomegaly; and debilitating systemic symptoms [1]. PPV-MF and PET-MF are therefore considered to be a natural evolution of these neoplasms, with median time to transformation of 7–20 years from PV/ET diagnosis [2], [3], [4], [5], [6]. The cumulative incidence of PPV-MF and PET-MF at 15 years has been reported to be between 5 and 14% for PV and 1.6-9% for ET [2], [7], [8], [9]. Although multiple factors have been reported to influence the rate of transformation, leukocytosis >15 × 10 9 is the most consistently reported factor [10]. Histopathologic findings in the bone marrow of PET/PPV-MF and PMF patients share overlapping features, and clinical characteristics are also very similar, with a typical picture of bone marrow failure, splenomegaly and chronic inflammatory status, leading to worsening quality of life and cachexia.

Few studies have specifically focused on comparing biologic, clinical and prognostic features of PET/PPV-MF patients [11], [12], [13] with those of patients with PMF and findings have been conflicting [13], [14], [15], [16], [17], [18].

Prognostication in PPV-MF and PET-MF is evolving, and evidence suggests that the International Prognostic Score System (IPSS), an established prognostication tool in PMF, can’t accurately discriminate different risk categories in PET/PPV-MF patients. However, there is a paucity of data describing clinical characteristics, disease course and outcomes of patients with PET/PPV-MF. In clinical practice, PET/PPV-MF patients are managed similarly to those with PMF; however, whether this practice should change is not known. Here, we describe the clinicopathologic characteristics of patients with PET/PPV-MF and compare their clinical, biologic, and prognostic features with those of PMF patients seen at our center.

Section snippets

Patients and methods

We retrospectively reviewed the medical records of 1099 patients with MF who were referred to our institution between 1984 and 2013. PMF was diagnosed according to 2008 World Health Organization (WHO) criteria. PET/PPV-MF was diagnosed according to The International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria, which requires a previously documented World Health Organization (WHO)-defined diagnosis of PV or ET and the presence of bone marrow fibrosis grade  2

Demographics and clinic-pathological characteristics

A total of 1099 patients (755 PMF, 181 PPV-MF, 163 PET-MF) were included in our study (Table 1). Median time to presentation from MF diagnosis was significantly longer in patients with PMF than in those with PPV-MF and PET-MF (4 vs 1 vs 2 months, p < 0.001). Of 1099 patients, 595 (375 PMF, 122 PPV-MF, and 98 PET-MF) presented to our institution within 3 months from MF diagnosis and were previously untreated. Among patients who presented to our institution more than 3 months from diagnosis, the

Discussion

In this study, we compared clinical characteristics and outcomes of 1099 patients with PPV-MF, PET-MF, and PMF from a single institution. Some important differences in overall survival and prognostic factors were identified. We found that age > 65 years, hemoglobin < 10 g/dL and poor performance status with significant symptoms were the most detrimental for OS of patients with PPV-MF, while hemoglobin < 10 g/dL, peripheral blood blasts  1% and platelets <100 × 109/L were prognostic factors for those

Funding source

This work was supported in part by a Cancer Center Support Grant to MD Anderson Cancer Center (P30 CA016672) from the National Cancer Institute

Acknowledgments

This work was supported in part by a Cancer Center Support Grant to The University of Texas MD Anderson Cancer Center (P30 CA016672) from the US National Cancer Institute.

REFERENCES (24)

  • A. Alvarez-Larran et al.

    Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients

    Leukemia

    (2007)
  • R. Marchioli et al.

    Vascular and neoplastic risk in a large cohort of patients with polycythemia vera

    J. Clin. Oncol.

    (2005)
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