Evidence that Prefibrotic Myelofibrosis Is Aligned along a Clinical and Biological Continuum Featuring Primary Myelofibrosis

Abstract

PurposeIn the WHO diagnostic classification, prefibrotic myelofibrosis (pre-MF) is included in the category of primary myelofibrosis (PMF). However, strong evidence for this position is lacking.Patients and MethodsWe investigated whether pre-MF may be aligned along a clinical and biological continuum in 683 consecutive patients who received a WHO diagnosis of PMF.ResultsAs compared with PMF-fibrotic type, pre-MF (132 cases) showed female dominance, younger age, higher hemoglobin, higher platelet count, lower white blood cell count, smaller spleen index and higher incidence of splanchnic vein thrombosis. Female to male ratio and hemoglobin steadily decreased, while age increased from pre-MF to PMF- fibrotic type with early and to advanced bone marrow (BM) fibrosis. Likely, circulating CD34+ cells, LDH levels, and frequency of chromosomal abnormalities increased, while CXCR4 expression on CD34+ cells and serum cholesterol decreased along the continuum of BM fibrosis. Median survival of the entire cohort of PMF cases was 21 years. Ninety-eight, eighty-one and fifty-six percent of patients with pre-MF, PMF-fibrotic type with early and with advanced BM fibrosis, respectively, were alive at 10 years from diagnosis.ConclusionPre-MF is a presentation mode of PMF with a very indolent phenotype. The major consequences of this contention is a new clinical vision of PMF, and the need to improve prognosis prediction of the disease.

Increased plasma nicotinamide phosphoribosyltransferase is associated with a hyperproliferative phenotype and restrains disease progression in MPN‐associated myelofibrosis

“…Since younger age in MF is mostly associated with an indolent disease phenotype characterized by normal or increased hemoglobin value and thrombocytosis [38], by multivariable analysis we established that younger age and increasing platelet count were both independent covariates associated with higher eNAMPT levels. These data indicate that increased level of eNAMPT have a role in the mechanism by which young patients in MPN-associated myelofibrosis tend to have a hyperproliferative phenotype of the disease.…”

Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms

“…Similarly, it has been suggested that prefibrotic MF may represent a transitional point between ET and MF. 129 Our understanding of the biological complexity underpinning MPNs and how this relates to clinical parameters and outcomes continues to improve. The ongoing challenge will be to integrate our understanding of these molecular processes into everyday clinical practice in order to allow for better refinement of our diagnostic classifications as well as improved prognostication and therapeutics.…”

High concordance in grading reticulin fibrosis and cellularity in patients with myeloproliferative neoplasms

“…[1][2][3][4][5] These myeloproliferative neoplasms have highly variable propensities to either present with or to develop progressive bone marrow fibrosis: this fibrosing process is intrinsic to primary myelofibrosis and affects a significant subset of polycythemia vera patients and a very small subset of essential thrombocythemia patients. [6][7][8][9][10][11][12] Bone marrow fibrosis is measured by reticulin and trichrome stains of the bone marrow trephine biopsy and is graded on a semiquantitative scale. 13 The classification proposed by the World Health Organization (WHO) and updated in 2008 employs the European Consensus System to grade bone marrow fibrosis, which has four possible grades (0, 1, 2, and 3); distinction between these levels is based on the number, density, and thickness of silver-stained reticulin fibers as assessed by the pathologist (Table 1).…”