Abstract
Clonal cytogenetic evolution (CE) (i.e., acquisition of new chromosomal aberrations over time) is relevant for the progression of myelodysplastic syndromes (MDS). We performed detailed analysis of CE in 729 patients with MDS and related disorders. Patients with CE showed shorter survival (median OS 18.0 versus 53.9 months; P < 0.01), higher leukemic transformation rate (48.0% versus 21.4%; P < 0.01) and shorter intervals to leukemic transformation (P < 0.01). Two main CE patterns were detected: early versus late CE (median onset 5.3 versus 21.9 months; P < 0.01) with worse survival outcomes for early CE. In the case of CE, del (7q)/−7 (P = 0.020) and del (17p) (P = 0.002) were especially unfavorable. Extending the evolution patterns from Tricot et al. (1985) forming five subgroups, prognosis was best (median OS not reached) in patients with “transient clones/changing clone size”, whereas those with “CE at diagnosis” showed very poor outcomes (P < 0.01 for comparison of all). Detailed sequential cytogenetic analysis during follow-up improves prognostication in MDS patients and acknowledges the dynamic biology of the disease. Evidence, time-point, and patterns of cytogenetic clonal evolution should be included into future prognostic scoring systems for MDS.
Highlights
1234567890():,; 1234567890():,; Introduction In around 50% of patients with myelodysplastic syndromes (MDS), clonal cytogenetic abnormalities are detectable by conventional chromosome banding (CCB) from bone marrow metaphases[1,2,3] The karyotype is highly significant for prognostication[2,3,4,5,6] and therapy allocation in patients with MDS and plays a fundamental role for the International Prognostic Scoring System (IPSS)[4], its revised form, the IPSS-R6,7 and the WHO adapted Prognostic Scoring System[8,9]
When only cytogenetically aberrant cases were considered, cytogenetic evolution (CE) occurred by a frequency of 25.8% (n = 92/356)
Cytogenetic aberrations within clonal evolution We focused on the 18 patients in whom CE
Summary
In around 50% of patients with myelodysplastic syndromes (MDS), clonal cytogenetic abnormalities are detectable by conventional chromosome banding (CCB) from bone marrow metaphases[1,2,3] The karyotype is highly significant for prognostication[2,3,4,5,6] and therapy allocation in patients with MDS and plays a fundamental role for the International Prognostic Scoring System (IPSS)[4], its revised form, the IPSS-R6,7 and the WHO adapted Prognostic Scoring System[8,9]. Therapeutic options in patients with MDS are highly variable including supportive measures, targeted approaches such as lenalidomide in MDS with isolated 5q deletion[12], and disease-modifying approaches such as azacitidine or decitabine[13,14]. Complex karyotypes (defined by at least three independent clonal cytogenetic changes)[17] amount to 15%
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