New Criteria Reclassified a Subset of Patients With MDS as Having Oligo-monocytic CMML

Updated diagnostic thresholds propose redefining oligo-monocytic chronic myelomonocytic leukemia (O-CMML) as a distinct clinical entity based on an absolute monocyte count of 0.5 to 1.0 × 10⁹/L, a change that reshapes the current understanding of myelodysplastic syndrome (MDS) and CMML. 

New World Health Organization (WHO) and International Consensus Classification (ICC) 2022 guidelines propose lowering the threshold for diagnosis of CMML to an absolute monocyte count of 0.5 × 10⁹/L or higher as long as monocytes make up less than 10% of the differential count with supporting evidence of clonality, dysplasia, classical monocytosis, and/or cytopenia.^1,2 While reflecting evolving insights into hematologic disorders, these guidelines may have implications for clinical practice and complicate trial eligibility and prognostic assessment. In a recent study, Rami S. Komrokji, MD, Moffitt Cancer Center, Tampa, Florida, and colleagues interrogated the clinical and molecular features of the newly reclassified clinical subgroup O-CMML and compared them with MDS and CMML.³

The study included participants from two large molecularly annotated cohorts of patients with MDS and CMML who met the new CMML criteria but were not included in the CMML database (WHO 2017 criteria).

In this comprehensive analysis of molecularly annotated cohorts, 25% of patients with MDS were reclassified as having O-CMML under the new criteria. Compared with patients who have classical dysplastic and proliferative forms of CMML, those with newly reclassified O-CMML demonstrated a genomic landscape more akin to that of MDS, including higher TP53 and DNMT3A mutation frequencies. Notably, SF3B1 mutations were enriched in newly reclassified O-CMML, appearing in 29% of cases, and outcomes for these patients were closer to MDS-SF3B1 than CMML-SF3B1. Clinical outcomes for patients with newly reclassified O-CMML revealed intermediate features between MDS and CMML. Acute myeloid leukemia transformation rates were 20% for O-CMML, compared with 30% for MDS and 28% for proliferative CMML, with worse outcomes for patients with O-CMML relative to MDS (hazard ratio [HR], 1.2) but better outcomes compared with dysplastic CMML (HR, 1.3) and proliferative CMML (HR, 1.87).

Dr. Komrokji summarized: “The findings highlight the challenges of accurately classifying hematologic disorders. Including O-CMML as CMML could potentially complicate treatment strategies and trial design, particularly given the distinct molecular and clinical profiles.” Limitations of the study, including its retrospective nature and lack of longitudinal monocyte subset data, emphasize the need for further research.

References

1. Arber DA, Orazi A, Hasserjian R, et al. International consensus classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140(11):1200–1228. doi: 10.1182/blood.2022015850
2. Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36:1703–1719. doi: 10.1038/s41375-022-01620-2
3. Komrokji RS, Komrokji Z, Al Ali NH, et al. CMML is in the eye of the Be_WHO_Lder: interrogating the newly proposed entity of oligomonocytic chronic myelomonocytic leukemia (O-CMML): MDS or CMML? Abstract #1004. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.