Has Cytogenetic Evolution Any Prognostic Relevance in Myelodysplastic Syndromes (MDS)? A Study on 153 Patients.

Defining the incidence and the prognostic relevance of cytogenetic evolution (CE) in MDS, excluding any effect of the primary defect and other well-known prognostic variables, are the main goals of the present study which included 153 patients (pts) examined between January 1990 and December 2005. They were 73 females and 80 males with a median age of 60.5 years (inter-quartile, IQ, range:49.8-68.3). FAB, IPSS score, IPSS cytogenetic categories were applied to all pts, WHO to 142. On clinical diagnosis 94 pts presented an abnormal karyotype. Median follow-up was 45.2 months (IQ range:22.8-75.6). At the time of analyses 107pts (69.9%) are alive and 46 (30.0%) have died. A clinical progression (CP) occurred in 65 (42.4%) pts and a CE in 47 (30.7%). Median progression-free survival was 65.2 months (IQ range:16.6-not reached). When a Cox model analysed CE as a time-dependent variable predicting disease outcome, a true CE occurred in a total of 40 pts who presented a survival significantly shorter than that of pts without such an evolution (Hazard ratio, HR=7.1, p<0.000 [95% confid. intervals, CI=3.9-12.8]), death rates 47.5 (95% CI=30.3-74.4) versus 5.4 (95%CI=3.7-7.9). A bivariable analysis was applied in order to test whether the relevance of CE remained significant also when it was adjusted for other variables with a well-known impact on disease outcome. This investigation revealed that CE predicted survival independently of the presence of the primary defect (HR=6.6, p<0.000 [95%CI=3.6-12.0]), IPSS cytogenetic categories (HR=6.6, p<0.000 [95%CI=3.6-12.2]), FAB subtypes (HR=4.2, p<0.000 [95%CI=2.3-7.8]), WHO subtypes (HR=4.4, p<0.000 [95%CI=2.3-8.5]) and IPSS categories (HR=3.8, p<0.000 [95%CI=2.0-7.2]). No single secondary defect had a significant impact on survival. When considering CP, the 40 pts with CE presented a risk of disease progression higher than that of pts without CE (HR=35.8, p<0.000 [95%CI=20.6-62.1]), progression rates: 183.9 (95% CI=129.3-261.5) versus 7.3 (95%CI=5.2-10.3). The relevance of CE remained significant when it was adjusted for the presence of primary cytogenetic aberrations (HR=33.9, p<0.000, [95% CI=19.1-60.0]). CE impact was much more significant in pts without than in those with primary defects: HR=61.8 (p<0.000, [95%CI=18.0-212.5]) versus 21.2 (p<0.000, [95%CI=11.1-40.3]). Bivariable analyses revealed that the impact of CE remained significant in all IPSS cytogenetic categories (HR=32.8, p<0.0000 [95%CI=18.6-57.8]), FAB subtypes (HR=21.6, p<0.000 [95%CI=12.2-38.1]), WHO subtypes (HR=27.7, p<0.0000 [95%CI=14.6-52.8]) and IPSS categories (HR=27.3,p<0.0000 [95%CI=14.6-50.9]). Monosomy 7, del(7q) and del(17p) were the secondary defects significantly effecting the risk of disease progression (p<0.0000). In conclusion, in our series CE presented:

• i) an incidence of 30%;

• ii) a significant impact on survival independently of the primary defect, FAB/WHO classifications, IPSS score and IPSS cytogenetic categories;

• iii) a significant impact on the risk of CP independently of the primary defect, FAB/WHO classification, IPSS score and IPSS cytogenetic categories.

In addition, monosomy 7, del(7q) and del(17p) were the secondary defects significantly effecting the risk of CP.