Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

Abstract

Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy.

Validation of the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes in chronic myelomonocytic leukaemia: A novel approach for improved risk stratification

“…Yet, as our understanding of the CMML genetic tapestry deepens, it is becoming evident that genetic mutations wield profound influence across the disease spectrum-from diagnosis and progression to prognosis and pharmacological responsiveness. [19][20][21] The AIPSS-MDS, while outpacing conventional models in its predictive capabilities, has potential avenues for enhancement. In the future, integrating genetic mutation data may elevate its prognostic accuracy, making it an even more potent tool.…”

“…Unlike its predecessors, the AIPSS‐MDS does not merely categorize; it excavates deeper nuances of its foundational variables, harnessing the prowess of random survival forests to yield a nuanced risk prediction unparalleled in its precision. Yet, as our understanding of the CMML genetic tapestry deepens, it is becoming evident that genetic mutations wield profound influence across the disease spectrum—from diagnosis and progression to prognosis and pharmacological responsiveness 19–21 . The AIPSS‐MDS, while outpacing conventional models in its predictive capabilities, has potential avenues for enhancement.…”

Characteristics and long‐term outcome in a large series of chronic myelomonocytic leukaemia patients including 104 formerly referred to as oligomonocytic

“…OM‐CMML referred to those patients who meet all the criteria required by the 2017 WHO classification for CMML diagnosis except for the absolute number of monocytes (≥0.5 and <1 × 10 9 /L). Cytogenetics was analysed on G‐banded metaphase cells and targeted next generation sequencing (NGS) was performed on genomic DNA with the Ion AmpliSeq™ AML Research Panel or Oncomine™ Myeloid Research Assay, as previously described 11 …”

“…Cytogenetics was analysed on G-banded metaphase cells and targeted next generation sequencing (NGS) was performed on genomic DNA with the Ion AmpliSeq™ AML Research Panel or Oncomine™ Myeloid Research Assay, as previously described. 11 Complete details are provided in Supplementary Methods.…”

Infrequent Presentations of Chronic NPM1-Mutated Myeloid Neoplasms: Clinicopathological Features of Eight Cases from a Single Institution and Review of the Literature

“…Patients with CMML carrying the NPM1 mutation presented at a relatively young age, with a median of 60 years (range, . This subgroup exhibited distinctive characteristics, including a median bone marrow blast count of 13% (10)(11)(12)(13)(14)(15)(16)(17)(18)(19), leukocytes of 15.7 × 10 9 (12.24-30.6), a platelet count of 98 × 10 9 (35-110), and a median hemoglobin concentration of 85 g/L (49-138). Among these five patients, three were eligible for intensive chemotherapy and attained a complete response with a significant reduction in NPM1 ratio.…”