The 2016 WHO versus 2008 WHO Criteria for the Diagnosis of Chronic Myelomonocytic Leukemia

Abstract

The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×109/L and ≥10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification. Application of the 2016 WHO criteria resulted in the exclusion of three (8%) patients who did not fulfill the relative monocytosis criterion and eight (21%) patients with an MPN-associated mutation. These 11 patients formed the 2016 WHO others group; the remaining 27 formed the 2016 WHO CMML group. The significant difference in the platelet count and monocyte percentage between the two groups indicated that the 2016 WHO criteria lead to a more homogenous and improved definition of CMML compared with the 2008 WHO criteria, which may have led to over-diagnosis of CMML. More widespread use of molecular tests and more sophisticated clinical and morphological evaluations are necessary to diagnose CMML accurately.

Proposed diagnostic criteria for classical chronic myelomonocytic leukemia (CMML), CMML variants and pre-CMML conditions

“…15-19 Moreover, contrasting the 2008 WHO classification, the diagnosis of CMML now requires both an absolute monocytosis (≥1×10 9 /L) and relative monocytosis (≥10% of leukocytes) in the peripheral blood (PB). 15-19 In the 2008 and 2016 update of the WHO classification, CMML can only be diagnosed per definition when rearrangements in PDGFRA , PDGFRB or FGFR1 genes have been excluded, and in the 2016 update, the PCM1-JAK2 fusion gene was added as an excluding criterion. 14-16,19 These molecular aberrations are commonly found in eosinophilia-associated neoplasms such as chronic eosinophilic leukemia.…”

“…15-19 In the 2008 and 2016 update of the WHO classification, CMML can only be diagnosed per definition when rearrangements in PDGFRA , PDGFRB or FGFR1 genes have been excluded, and in the 2016 update, the PCM1-JAK2 fusion gene was added as an excluding criterion. 14-16,19 These molecular aberrations are commonly found in eosinophilia-associated neoplasms such as chronic eosinophilic leukemia. 20,21 However, CMML is also listed as an underlying variant in these molecular ‘entities’ in the WHO classification system.…”

“…In fact, classical CMML should be split into CMML-0, CMML-1 and CMML-2 based on the blast cell count ( Online Supplementary Table S2 ). 15-19 In addition, CMML can be divided into a dysplastic variant and a proliferative variant based on leukocyte counts (threshold: 13x10 9 /L) ( Online Supplementary Table S2 ). The resulting grading system defines six distinct CMML variants with variable clinical outcome.…”

Use of Tocilizumab in Management of Post-Operative Myelomonocytic Leukemoid Reaction

“…The exact mechanism of PO-MMLR has not been fully elucidated. Studies have shown that patients with CMML have increased concentrations of pro-inflammatory cytokines including IL-8, IL-10, IL-1 receptor antagonist, tumor necrosis factor α, and IL-6 compared with healthy controls [6] , [7] , [8] , [9] . We hypothesize that in our patient the increased risk of PO-MMLR was perhaps due to the presence of TET-2 mutation.…”

Needs survey on the priority given to periodical medical examination items among occupational physicians in Japan

“…In Budget Plan 2, the non-statutory items with a selection rate >80%, with the exception of serum creatinine, were white blood cell count (92%), uric acid (89%), and fecal occult blood reaction (81%). White blood cell count can be used for the detection of leukemia and hematologic diseases 24) , and is also useful for the risk and aptitude assessments in pathogen-related businesses and the hospitality industry, as well as to provide health guidance to smokers with an increased white blood cell count 25) . Uric acid with poorly controlled hyperuricemia can cause gout attacks, thereby affecting work productivity by unexpected absences and pain.…”