Validation of the 2017 revision of the WHO chronic myelomonocytic Leukemia categories

Abstract

The 2017 revision of the World Health Organization (WHO) classification includes substantial changes to the subclassification of chronic myelomonocytic leukemia (CMML): (1) a 3-tiered blast-based scheme including a novel “CMML-0” category replacing a 2-tiered system in place since 2001 and (2) 2 CMML subtypes, myelodysplastic (MDS-CMML) and myeloproliferative (MP-CMML), based on a white blood cell count cutoff of 13 3 109/L. The clinical utility of this subclassification scheme, particularly the expansion of blast-based subgroups, has not been validated. In this study, a large single-institution CMML patient cohort (n 5 629) was used to assess the prognostic impact of the newly proposed categories. Patients were risk stratified according to the CMML-specific Prognostic Scoring System (CPSS) and the MD Anderson Prognostic Scoring System. MP-CMML patients had significantly shorter overall survival (OS; P, .0001; hazard ratio: 0.53, 95% confidence interval: 0.42-0.65) and median duration to acute myeloid leukemia (AML) transformation (P, .0001; 15.2 vs 22.0 months) compared with MDS-CMML patients. The CMML-0 group included 36.4% patients with higher risk CPSS categories and 11.2% of patients with high-risk cytogenetics. Among treatment-naïve patients (n 5 499), there was a marginal difference in OS between the CMML-0 and CMML-12017 subgroups (P 5 .0552). The WHO 2017 blast-based categories were not associated with AML-free survival. Incorporation of the WHO 2017 blast-based subgroups in a modified CPSS scheme had a neutral effect and did not improve its prognostic strength. Our data support the inclusion of MP-CMML and MDS-CMML subtypes in the WHO 2017 revision. Although of some utility in MP-CMML, the 3-tiered blast-based system is not well supported in this study.