How I diagnose and treat chronic myelomonocytic leukemia

Abstract

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/myeloproliferative overlap neoplasm characterized by sustained peripheral blood monocytosis and an inherent risk for transformation to acute myeloid leukemia (AML; 15-30% over 3-5 years). While CMML is morphologically classified in CMML-0,1 and 2 based on peripheral blood and bone marrow promonocyte/blast counts, a more clinically relevant classification into dysplastic (dCMML) and proliferative (pCMML) subtypes, based on the presenting white blood cell count is helpful in prognostication and therapeutics. CMML is a neoplasm associated with aging, occurring on the background of clonal hematopoiesis, with TET2 and SRSF2 mutations being early initiating events. The subsequent acquisitions of ASXL1, RUNX1, SF3B1 and DNMT3A mutations usually give rise to dCMML, while ASXL1, JAK2V617F and RAS pathway mutations give rise to pCMML. Patients with pCMML have a more aggressive course with higher rates of AML transformation. Allogeneic stem cell transplant remains the only potential cure for CMML, however, given the advanced median age at presentation (73 years) and comorbidities, is an option to only a few affected patients (10%). While DNA methyltransferase inhibitors are approved for the management of CMML, the overall response rates are 40-50%, with true complete remission rates of

A three‐gene leukaemic stem cell signature score is robustly prognostic in chronic myelomonocytic leukaemia

“…Hitherto, mutant ASXL1 has proved the only consistent adversely prognostic molecular feature in CMML, appearing in three existing prognostic models. 11 Our LSC-3 score both outperformed these current models and usefully stratified patients' prognosis within both ASXL1 mutant and wild-type subgroups.…”

“…In subgroup analyses the LSC‐3 score retained strong prognostic value for LFS and OS in CMML‐1 (Figure S3A,B), CMML‐2 (Figure S3C,D), and in dysplastic (Figure 1C) and proliferative subgroups (Figure S4). ASXL1 mutations have been consistently associated with poor prognosis in CMML and are incorporated into current prognostic systems 11 . In ASXL1 ‐unmutated patients, high LSC‐3 score robustly correlated with inferior LFS and OS (Figure 1D).…”

“…ASXL1 mutations have been consistently associated with poor prognosis in CMML and are incorporated into current prognostic systems. 11 In ASXL1-unmutated patients, high LSC-3 score robustly correlated with inferior LFS and OS (Figure 1D). Amongst ASXL1-mutated patients, high LSC-3 score was associated with significantly worse OS (Figure S5A,B).…”

Chronic myelomonocytic leukemia in a 72-year-old male from Nepal: A case report

“…Risk stratification in CMML can be done by various prognostic models for CMML such as MD Anderson Prognostic Score (MDAPS), CMML-Specific Cytogenetic Risk Stratification (CPSS), Mayo-French Cytogenetic Risk Stratification System, Mayo Molecular Model (MMM), and CMML-Specific Prognostic Scoring System (CPSS-Mol) to name some few 2 , 9 .…”

Prognostic Implication of Early Minimal Residual Disease Evaluation in Patients with Chronic Myelomonocytic Leukemia

“…Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that overlaps the features of myelodysplastic syndromes and myeloproliferative neoplasms (MDS/MPN), which carrying an inherent risk for developing blast transformation and the approximated incidence is 15%-30% over 3-5 years. (1,2) Numerous pretreatment prognostic models are well established so far by bone marrow (BM) blasts, abnormal karyotypes, and genetic mutations, which closely associated with clinical prognosis of patients with newly diagnosed CMML and developing adapted treatment strategy. (3,4) Response criterias proposed by International Working Group (IWG) in 2015 according to morphologic analysis also provides much disease speci c prognostic information and re ects chemotherapy sensitivity of leukemia.…”