TY - JOUR
T1 - The prognostic relevance of serum lactate dehydrogenase and mild bone marrow reticulin fibrosis in essential thrombocythemia
AU - Mudireddy, Mythri
AU - Barraco, Daniela
AU - Hanson, Curtis A.
AU - Pardanani, Animesh
AU - Gangat, Naseema
AU - Tefferi, Ayalew
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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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U2 - 10.1002/ajh.24689
DO - 10.1002/ajh.24689
M3 - Article
C2 - 28211153
AN - SCOPUS:85015709574
SN - 0361-8609
VL - 92
SP - 454
EP - 459
JO - American journal of hematology
JF - American journal of hematology
IS - 5
ER -