Chronic myelomonocytic leukemia - a review

ABSTRACT

Introduction

Chronic myelomonocytic leukemia (CMML) is a clonal myeloid neoplasm, denoted by overlapping myelodysplastic and myeloproliferative features, with poor overall survival and high transformation rate to acute myeloid leukemia.

Areas covered

This review, following a thorough Medline search of pertinent published literature, discusses the diagnostic criteria, the pathogenesis, and the complex genetic landscape of the disease. Prognostication, response criteria, therapeutic management of patients, efficacy of established and novel treatment modalities are thoroughly reviewed.

Expert opinion

Cytogenetic abnormalities and mutations in genes involved in epigenetic and transcriptional regulation, and cell-signaling are abundant in CMML and implicated in its complex pathogenesis. As presence of these mutations carry a prognostic impact, they are increasingly incorporated in risk-stratification schemes. Novel response criteria have been proposed, considering the unique features of the disease. Although allogeneic hematopoietic stem cell transplantation remains the only treatment with curative intent, it is reserved for a minority of patients; therefore, there is an unmet need for optimizing treatment modalities, such as hypomethylating agents, and introducing novel agents, which could substantially improve survival and quality of life of CMML patients. Clinical trials dedicated specifically to CMML are needed to explore the efficacy and safety of novel treatment modalities.

KEYWORDS:

• Chronic myelomonocytic leukemia
• cmml
• myelodysplastic/myeloproliferative disease
• asxl1
• tet2
• hypomethylating agents

Article highlights

• There is an increasing understanding of CMML pathogenesis, age-dependent DNA damage drives the emergence of clone harboring a driver mutation in TET2 or ASXL1, acquisition of secondary mutations contributes to expansion of the myelomonocytic compartment and myelodysplasia.

• Gene mutations correlate to overall and leukemia-free survival and are incorporated in modern risk-stratification models.

• Disease-specific response criteria have been proposed, taking into account the unique features of the disease.

• Allogeneic transplantation is the only curative treatment modality; however, it confers high treatment-related mortality.

• Other treatment options, as hypomethylating agents offer a suboptimal survival benefit, highlighting the need for novel treatment modalities, currently investigated in clinical trials.

• Clinical trials focusing specifically on CMML are needed to explore the efficacy of novel therapeutic agents and allow for the optimization of management of CMML patients

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.