Incidence and prognostic significance of karyotype abnormalities in de novo primary myelodysplastic syndromes: a study on 331 patients from a single institution

Abstract

The impact of clinical parameters, International Prognostic Scoring System (IPSS) scores/cytogenetic categories, and some single cytogenetic defects on overall survival (OS) and time to myelodysplastic syndromes (MDS)/AML progression (progression-free interval (PFI)) was evaluated in 331 MDS patients. Statistical analysis demonstrated that OS and PFI were significantly affected by all these parameters. Since single 7q-showed a better survival than the poor IPSS cytogenetic category (P ¼ 0.009), it was considered as a new prognostic entity ('modified IPSS categories'). In multivariate analysis OS was significantly influenced by age, marrow blast cell percentage, number of cytopenias and either modified or standard IPSS cytogenetic categories; hazard ratios for MDS/AML progression were influenced by all the former, except for age and cytopenias. Multivariate analysis of del (7)(q31q35) confirmed the results of univariate analysis, but the Akaike Information Criterion showed no difference in evaluating OS and PFI between the modified and standard IPSS cytogenetic grouping. In conclusion, (i) chromosome defects as grouped by IPSS and blast cell percentage are the most relevant parameters for predicting OS and PFI; (ii) the prognostic power of the IPSS cytogenetic grouping is not ameliorated by the introduction of del(7)(q31q35) as a new entity; (iii) complex karyotypes have a prognostic value independent of blast cell percentage.

Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution

“…In our series, clonal chromosomal abnormalities were revealed in 53.8% of the 630 de novo consecutive MDS patients. This frequency is similar to that reported by other studies [3][4][5][6][7][8][9][10][11][12][13]16,17], even if it should be underlined that our study did not include patients diagnosed as RAEB in transformation (RAEB-t), now considered AML by the WHO classification. Instead, the NCCSS study [17] also analyzed RAEB-t patients, as the exclusion of this MDS FAB subtype led to a statistically lower risk in the entire sample without affecting the relative position of the five prognostic subgroups.…”

“…The IPSS [8], the Spanish MDS Cytogenetic Working Group [10] and another study [16] have reported that del(7q) and 27 present a similar poor OS and a similar high risk of MDS/AML evolution. In contrast, the GA data set [13] and other reports [11,12,37] have revealed that isolated del(7q) and 27 were associated with an intermediate and a poor clinical outcome respectively. In particular, two previous studies by our own group [11,12] revealed that in univariate and multivariate analyzes del(7q) was associated with a survival probability better than that of the poor IPSS cytogenetic category and similar to that of the intermediate category, whereas the risk of MDS/AML evolution was similar to those of both IPSS cytogenetic categories.…”

“…Despite the efforts of many researchers [6][7][8][9][10][11][12][13]16,20], the prognostic significance of rare single chromosomal defects, double defects and unrelated clones, which flag the extreme heterogeneity of the MDS cytogenetic pattern [2,21,[28][29][30][31]41], has remained ill defined. In fact, most of the aforementioned studies provided conflicting results due to the small number of patients studied.…”

“…These disorders show substantial clinical variability, ranging from stability for 10 or more years to death due to cytopenias or evolution into acute myeloid leukaemia (AML) within a few months [2]. To more precisely identify patients with markedly different clinical outcomes, over the past 15 years various prognostic scoring systems have been developed and applied [3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The International Prognostic Scoring System (IPSS) [8] was that most commonly used and has been now revised [17][18][19].…”

“…Thus, these latter defects, which flag the extreme cytogenetic heterogeneity of MDS, should be included within a more precise cytogenetic scoring system [21]. In the last 10 years, large patient series have provided some relevant information on rare isolated abnormalities [9][10][11][12][13], but very few have provided information on combined defects [10,13]. In addition, it has become evident that the clinical outcome of patients with a complex karyotype, previously defined by the presence of 3 defects, worsens with an increase in the number of chromosomal defects [13,20,21].…”