Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia

Abstract

In older patients with chronic myelomonocytic leukaemia (CMML) and limited life expectancy due to age and or comorbidities, it is particularly important to consider the risk of transformation for individualised treatment decisions. There is limited information on potential differences between younger and older CMML patients regarding the cumulative risk of transformation as well as haematological, molecular and biologic characteristics. We analysed data from the Austrian Biodatabase for CMML (ABCMML) to compare these parameters in 518 CMML patients. Categorisation of patients into 3 age‐related groups: <60 years, 60‐79 years and ≥80 years, showed a significantly lower risk of transformation at higher age by competing risk analysis, with a 4‐year risk of 39%, 23% and 13%, respectively (P < .0001). The lower probability of transformation was associated with a lower percentage of blast cells in the peripheral blood (PB) of older patients. Furthermore, we provide a simple score based on age, PB blasts and platelet counts that allowed us to define subgroups of CMML patients with a different cumulative transformation risk, including a low‐risk group with a transformation risk of only 5%. Our findings may facilitate reasonable treatment decisions in elderly patients with CMML.

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

“…Many of our findings are along the lines of previous reports, including patient characteristics [ 8 , 10 , 11 , 22 , 32 , 37 , 38 , 39 , 40 ] and median OS (34 months) [ 8 , 9 , 40 ]. OS was longer in younger patients ( p = 0.002), those with low cytogenetic risk ( p < 0.001), and those with the FAB MDS phenotype ( p = 0.04), as previously reported [ 8 , 40 ].…”

“…The percentage of patients who progressed to AML in our study was also along the lines of previous reports [ 11 , 22 , 47 , 49 ]. The risk of AML transformation depends on the transformative aggressiveness of CMML and on the competing risk of dying before transformation, usually from comorbidities or consequences of cytopenia [ 37 ]. Findings in our cohort confirm the capacity of dichotomized CPPS and CPSS-Mol scores to discriminate between patients with low and high risk of AML transformation [ 10 , 11 ].…”

Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches

“…Mutations in the transcription regulators RUNX1, NPM1, and TP53 have also been found in CMML (9,30,31). Table 1 shows the frequencies of gene mutations in 3 different CMML cohorts in which comprehensive molecular analyses has been reported (9,11,32). Considering all molecular data reported mutations in TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and RAS pathway (~30%) are most common (15) but no molecular aberration is specific of this entity, as they can be detected with different frequencies in other myeloid neoplasms (33).…”

“…Thus, mice carrying a mutation in the RING finger domain of c-CBL develop a myeloproliferative disease involving hematopoietic progenitors that show increased FLT3 signaling (67). The incidence of molecular aberrations of the CBL gene has been reported from 10-14% (9,11,32) and thus is more common than that of the FLT3 gene. Therefore, CMML patients with mutations in the CBL gene could be potential candidates for studies with FLT3 inhibitors.…”

“…CMML is further subclassified by WHO into three groups based on blast equivalent (blasts plus promonocytes) in peripheral blood (PB) and bone marrow (BM) as follows: CMML-0 if PB <2% and BM <5% blast equivalent, CMML-1 if PB 2-4% or BM 5-9% blast equivalent, and CMML-2 if PB 5-19% or BM 10-19% blast equivalent, and/or Auer rods are present (6). The median survival of reported series is highly variable indicating a significant clinical heterogeneity of the disease (7)(8)(9)(10)(11)(12).…”