Comorbidities and mutations including single- and multihit TET2 mutations in relation to outcome in chronic myelomonocytic leukaemia-A population-based study

Abstract

To explore the relation between disease characteristics, comorbidities, mutations and overall survival (OS) in chronic myelomonocytic leukaemia (CMML), we collected data from a population-based cohort of 149 consecutive patients. TET2 mutation (TET2^MT) was associated with higher haemoglobin, less leucocytosis and longer OS compared to no TET2^MT (TET2^WT), despite patients being significantly older. Patients with multihit TET2^MT had the most favourable outcome (HR 0.55, CI 0.35-0.88, p < 0.05). Multihit TET2^MT was associated with lower lactate dehydrogenase and less monocytosis, indicating multihit TET2^MT as a separate disease entity. Autoimmune disease (AID) was present in 33.6% of patients, with no association to any mutations. In multivariable analysis, the number of TET2^MT was demonstrated to be an independent factor associated with improved OS, and RUNX1^MT, myeloproliferative CMML (CMML-MP), ECOG >0 and transfusion dependence remained significant adverse factors. Internal validation including cross-validation and correction for optimism consistently demonstrated that a prognostic model containing the number of TET2^MT, RUNX1, CMML-MP, ECOG >0 and transfusion dependence showed better calibration, discrimination and overall performance than CPSS-Mol in predicting OS. Importantly, the addition of TET2 mutation status to CPSS-Mol also improved the CPSS-Mol score performance. Taken together, TET2^MT status, especially multihit TET2^MT, defines a specific CMML phenotype and should be considered in future prognostic scores.

Keywords: TET2; autoimmune disease; comorbidities; thrombosis.