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

Abstract

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 × 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 = 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 = 499), there was a marginal difference in OS between the CMML-0 and CMML-12017 subgroups (P = .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.