CYTOGENETIC ANALYSIS HAS STRONG INDEPENDENT PROGNOSTIC VALUE IN DE-NOVO MYELODYSPLASTIC SYNDROMES AND CAN BE INCORPORATED IN A NEW SCORING SYSTEM - A REPORT ON 408 CASES

Although the prognostic value of cytogenetic analysis has previously b een demonstrated in myelodysplastic syndromes (MDS), karyotype had not been included in previously published scoring systems, such as Bourne mouth and Sanz's scores. We studied karyotype at diagnosis in 408 case s of de novo MDS (after excluding therapy-related MDS). Karyotypes wer e classified in 10 groups: normal; isolated del 5q; del 5q and other r earrangements; isolated +8; isolated -7 or del 7q; del 20q; isolated - Y; miscellaneous single rearrangements; -7 or del 7q and other rearran gements; miscellaneous complex rearrangements. Karyotypes were conside red complex when at least three chromosomes were rearranged. Complex k aryotypes included all patients with del 5q and other rearrangements, -7 or del 7q and other rearrangements, and miscellaneous complex rearr angements (i.e. three of the 10 groups). Median actuarial survival of the 408 patients was 28 months, and 90 patients (22%) progressed to ac ute myeloid leukemia (AML). For survival, bone marrow (BM) blasts, cir culating blasts, white blood cell (WBC), neutrophil count, platelet co unt, hemoglobin, age, sex, FAB classification, and Bournemouth and San z's scores had strong prognostic value. Cytogenetics also had strong p rognostic value. An unfavorable cytogenetic group (patients with compl ex karyotypes) was identified. On the other hand, although patients wi th isolated del 20q and del 5q had a somewhat better prognosis than ot her patients with non-complex cytogenetic findings, they could not be statistically individualized as a favorable group, possibly owing to t heir relatively limited number. By multivariete regression analysis, a three-variable new scoring system could be designed based on karyotye (1 point for complex karyotype; 0 for other groups), platelets (0 for > 75 x 10(9)/1; 1 for < 75 x 10(9)/1), and BM blasts (0 for < 5%, 1 f or 5-10%, 2 for > 10%). The total score (addition of points for the th ree variables) was able to separate patients in three groups with low (score 0) intermediate (score 1 or 2), and high risk (score 3 or 4) wh ich included 34%, 47%, and 19% of the patients, and had a median survi val of 55, 24, and 6 months, respectively (chi2 =110, p < 10(-4)). Thi s new score (Lille score) was able to subdivide risk groups according to Bournemouth and Sanz's scores into further subgroups of different p rognoses. For progression to AML, BM blasts, circulating blasts, WBC c ount, hemoglobin, FAB type, and karyotype had prognostic value by univ ariate analysis. By multivariate analysis, a predictive model based on karyotype and BM blasts could divide patients into three risk groups: low risk of progression to AML (absence of complex karyotype and BM b lasts less-than-or-equal-to 10%), intermediate risk (complex karyotype or BM blasts > 10%), and high risk (complex karyotype and BM blasts > 10%) with an estimated AML free percentage of 92%, 60%, and 32% at 2 years, respectively. Thus, karyotype has strong predictive value for s urvival and progression to AML in de novo MDS, and can be incorporated in multivariate scoring systems with one or two other variables.