Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes

Abstract

Summary. Recently, a consensus International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in the myelodysplastic syndromes (MDS) has been developed. However, the intermediate-risk cytogenetic subgroup de®ned by the IPSS includes a miscellaneous number of different single abnormalities for which real prognosis at present is uncertain. The main aims of this study were to evaluate in an independent series the prognostic value of the IPSS and to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in 640 patients. In univariate analyses, cases with single 1q abnormalities experienced poor survival, whereas those with trisomy 8 had a higher risk of acute leukaemic transformation than the remaining patients (P 0?004 and P 0?009 respectively).Patients with single del(12p) had a similar survival to patients with a normal karyotype and showed some trend for a better survival than other cases belonging to the IPSS intermediaterisk cytogenetic subgroup (P 0?045). Multivariate analyses demonstrated that IPSS cytogenetic prognostic subgroup, proportion of bone marrow blasts and haemoglobin level were the main prognostic factors for survival, and the ®rst two characteristics and platelet count were the best predictors of acute leukaemic transformation risk. A large international co-operative study should be carried out to clarify these ®ndings.

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.…”

“…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].…”

Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer’s perspective

“…Interstitial 5q deletions (del(5q)) are the most frequent chromosomal abnormalities in MDS present in 10% to 15% of MDS patients [6][7][8]. The prognosis is favorable with relatively low risk of transformation to AML [9;10] but the dependence on red blood cell (RBC) transfusions often has a negative effect on morbidity and mortality [10].…”