title: The prognostic relevance of serum lactate dehydrogenase and mild bone marrow reticulin fibrosis in essential thrombocythemia.
abstract: The 2016 World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (MPN) underscore the prognostically-relevant distinction between essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF). In addition, leukocytosis has been identified as an important prognostic marker in otherwise WHO-defined ET. However, controversy remains regarding the objectivity of morphologic criteria in distinguishing ET from pre-PMF and the precise prognostic cutoff values for leukocytosis. Serum lactate dehydrogenase (LDH) level might be a biologically more accurate measure of leukocyte turnover and a more sensitive marker of pre-PMF, in otherwise WHO-defined ET. In the current study of 183 consecutive patients with WHO-defined ET, the presence of grade 1 bone marrow (BM) fibrosis did not affect presenting clinical or laboratory features; in contrast, increased serum LDH at diagnosis was associated with leukocytosis (p = .002), thrombocytosis (p < .001), palpable splenomegaly (p = .03) and higher international prognostic score (IPSET) (p = .002); serum LDH did not correlate with BM fibrosis, JAK2/CALR/MPL or TET2/ASXL1 mutations. In univariate analysis, risk factors for survival included age ≥60 years (p = .002; HR 10.2, 95% CI 2.3-44.6), male sex (p = .02; HR 3.2, 95% CI 1.2-8.2), leukocyte count ≥15 × 109/L (p = .007; HR 4.7, 95% CI 1.5-14.6), and increased serum LDH (p = .002; HR 3.7, 95% CI 1.5-9.1), but not BM fibrosis (p = .17). In multivariable analysis, age, sex and serum LDH remained significant; serum LDH also remained significant, in the context of IPSET (p = .003) and in patients with leukocytosis (p = .003). We conclude that serum LDH level carries an independent prognostic value for survival in ET and might represent a biologically more accurate surrogate for leukocytosis.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mythri
authors.identifier: http://orcid.org/0000-0002-0550-8933
authors.initials: M
authors.lastname: Mudireddy
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Daniela
authors.initials: D
authors.lastname: Barraco
authors.affiliation: Division of Hematopathology, Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Naseema
authors.initials: N
authors.lastname: Gangat
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005260:Female; D006801:Humans; D045022:Lactate Dehydrogenases / Q000097:blood*; D007964:Leukocytosis / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000473:pathology*; D011379:Prognosis; D012155:Reticulin; D012307:Risk Factors; D013920:Thrombocythemia, Essential / Q000201:enzymology / Q000473:pathology*
chemical_list: D015415:Biomarkers; D012155:Reticulin; D045022:Lactate Dehydrogenases