WHO2016 Vs. WHO2008 Criteria for the Diagnosis of Chronic Myelomonocytic Leukemia

The new WHO2016 diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×10⁹/L and ≥10% of the WBC count) in peripheral blood (PB). In addition, they say that the presence of myeloproliferative neoplasms (MPN) features in the bone marrow (BM) and/or MPN-associated mutations (JAK2, CALR, or MPL) tend to support MPN with monocytosis rather than CMML. This study was performed to predict impact of the WHO2016 criteria in the diagnosis of CMML compared to the WHO2008 criteria.

We retrospectively reviewed clinical and laboratory data of 38 patients diagnosed of CMML (32 CMML-1, 6 CMML-2) using the WHO2008 criteria in 7 university hospitals from Jan 2012 to Jul 2016. The laboratory data included complete blood cell count with WBC differentials, BM morphology, cytogenetic study, and molecular genetic study such as BCR-ABL1 and mutational status of JAK2 V617F, JAK2 exon12, CALR, and MPL .

Male to female ratio was 2.8:1 and the mean age was 71±12 years. The medians of WBC count, hemoglobin, and platelet count were 22×10⁹/L, 90 g/L and 154×10⁹/L, respectively. The medians of monocyte, absolute monocyte count, blast, and nucleated red cell in PB were 20 (range 6~44)%, 4.1 (range 1.1~41.8)×10⁹/L, 1 (range 0~10)%, and 0 (range 0~5)%, respectively. The medians of cellularity, M:E ratio, blast, and monocyte in BM were 90 (range 25~100)%, 5 (range 2~26), 3 (range 0~17)%, and 7 (range 1~26)%, respectively. MPN-associated mutations were present in 8 (7 JAK2 V617F, 1 MPL) out of 21 patients tested and BCR-ABL1 was negative in all 27 patients tested. Coefficient of utilization for MPN-associated mutations at diagnosis, was very low (3~11%) except for JAK2 V617F (50%). WHO2008 criteria classified the patients into 32 CMML-1 and 6 CMML-2. WHO2016 criteria excluded 3 patients for not fulfilling relative monocytosis and 8 patients for having a MPN-associated mutation, and classified the 27 CMML patients into 17 CMML-0, 5 CMML-1, and 5 CMML-2. Sixteen was proliferative type (WBC count≥13×10⁹/L) of CMML and 11 dysplastic type (WBC count<13×10⁹/L). All patients with dysplastic type were CMML-0 except for two.

The relative monocytosis (≥10% of the WBC count) was not met in 3 (8%) patients and MPN-associated mutations were found in 8 (21%) patients. The WHO2008 criteria might over diagnose CMML. More aggressive use of molecular tests including MPN-associated mutation analyses and more sophisticated clinical or morphologic evaluation are necessary in order to make an accurate diagnosis of CMML.