World Health Organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes

Abstract

Summary This study correlated chromosomal defects with French–American–British (FAB)/World Health Organization (WHO) classification subtypes, proposed a revised International Prognostic Scoring System (IPSS) cytogenetic grouping; and established which classification, when used with the IPSS cytogenetic categories, best predicted clinical outcome in the myelodysplastic syndromes (MDS). A higher prevalence of chromosomal defects and distinct defects were observed in patients with multi‐lineage dysplasia and a blast cell percentage >10%. Abnormalities of the long arm of chromosome 3, del(7)(q31q35), trisomy 8, del(11)(q14q23), del(12p) and 20q‐ could be segregated from their respective IPSS cytogenetic categories and used to develop new cytogenetic subgroups. Clinical parameters, FAB/WHO classification, IPSS score and standard or revised cytogenetic categories were statistically relevant for overall survival (OS) and progression‐free intervals (PFI) and were included within five distinct multivariate models compared by the Akaike Information Criterion. To predict OS, the best models included age, WHO classification and standard or revised IPSS cytogenetic categories; to predict PFI, the best model included the same variables and revised cytogenetic categories. In conclusion, (i) the WHO classification was associated with a more homogeneous cytogenetic pattern than the FAB classification, (ii) WHO classification and standard/revised IPSS cytogenetic categories were much more effective than IPSS for predicting MDS clinical outcome, (iii) revised cytogenetic subgroups predicted PFI more effectively than standard categories.

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

“…The clinical and biological parameters which had a significant impact on OS and LFS after censoring and without censoring for specific treatments are listed in Tables III and IV. As already reported [12], after censoring age and gender have a statistically significant influence on OS only (HR 5 1.6 with P < 0.0001 and HR 5 1.7 with P < 0.0001, respectively), whereas anemia (Hb < 10 g/dL), thrombocytopenia (Plts <100/mL) and neutropenia (<1.8 3 10 9 /L) significantly affect OS (HR 5 1.7 and P < 0.0002; HR 5 1.9 and P < 0.0001; HR 5 1.6 and P < 0.0005) and LFS (HR 5 1.7 and P < 0.004; HR 5 2.1 and P < 0.0001; HR 5 2.4 and P < 0.0001). These variables were also strongly influenced by the bone marrow blast cell percentage.…”

“…All of the 630 consecutive de novo MDS patients, including 491 analyzed in a previous report [12], were diagnosed at the Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia between January 1990 and December 2010. MDS diagnosis was made according to the WHO criteria [1].…”

“…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].…”

“…The International Prognostic Scoring System (IPSS) [8] was that most commonly used and has been now revised [17][18][19]. Thus, cytogenetic abnormalities remain one of the major determinants of MDS pathogenesis, diagnosis, prognosis and guide any potential treatment decisions [12][13][14][15][16][17][18][19][20][21][22][23][24][25], however more sensitive techniques such as array Comparative Genomic Hybridization, Single Nucleotide Polymorphism arrays (SNP-a) and Next-Generation Sequencing are still used in the research setting only [26][27][28][29][30][31]. The IPSS precisely defines the prognostic value of the most frequent chromosomal defects, whereas it does not define rare or combined abnormalities, which are included within the intermediate category [8].…”

“…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].…”