Chronic Myelomonocytic Leukemia

Owing to its variable pathologic features and clinical course, chronic myelomonocytic leukemia (CMML) is both a diagnostic and a therapeutic challenge. The French-American-British (FAB) classification system included CMML as one of the five categories of myelodysplastic syndrome (1), and its definition of CMML as a disease characterized by absolute monocytosis is still used today. The FAB classification includes a wide spectrum of patients with cytopenias and ineffective hematopoiesis reminiscent of myelodysplastic syndromes(MDS)and those with leukocytosis and organ involvement typical of myeloproliferative disorders, suggesting differences in pathology. Based on expert opinion, the FAB group proposed the use of a white blood cell (WBC) count of 13 × 10⁹/L as an arbitrary cutoff point to separate CMML into “dysplastic” and “proliferative” varieties (2). The International Working Group followed the FAB recommendation (3) and excluded CMML patients with WBC >12 × 10⁹/L from the risk-oriented International Prognostic Scoring System for MDS (IPSS) (3), limiting its usefulness for assessing the expected outcomes of CMML patients(4, 5). The World Health Organization(WHO)included CMML in a category of mixed myelodysplastic/myeloproliferative disorders (MDS/MPD) (6). The prognostic significance of bone marrow and circulating blasts and eosinophilia led to the creation of further subcategories.

The major contribution of the FAB classification was the creation of a defined category of CMML. The unintended consequence of including CMML in the MDS group was that in reporting the results of clinical trials, data from patients with CMML were often combined with those from patients with high-risk MDS, which made it difficult to assess the impact specifically on CMML. The WHO classification, which further highlights distinct features of CMML, should encourage research and stimulate the initiation of clinical trials focusing specifically on CMML.