The prognostic relevance of serum lactate dehydrogenase and mild bone marrow reticulin fibrosis in essential thrombocythemia

Mythri Mudireddy, Daniela Barraco, Curtis A. Hanson, Animesh D Pardanani, Naseema Gangat, Ayalew Tefferi

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
JournalAmerican Journal of Hematology
DOIs
StateAccepted/In press - 2017

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Reticulin
Essential Thrombocythemia
Primary Myelofibrosis
L-Lactate Dehydrogenase
Leukocytosis
Serum
Thrombocytosis
Survival
Splenomegaly
Leukocyte Count
Leukocytes
Mutation

ASJC Scopus subject areas

  • Hematology

Cite this

The prognostic relevance of serum lactate dehydrogenase and mild bone marrow reticulin fibrosis in essential thrombocythemia. / Mudireddy, Mythri; Barraco, Daniela; Hanson, Curtis A.; Pardanani, Animesh D; Gangat, Naseema; Tefferi, Ayalew.

In: American Journal of Hematology, 2017.

Research output: Contribution to journalArticle

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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.",
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