New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge

Abstract

Purpose: The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the International Prognostic Scoring System (IPSS) in 1997, knowledge concerning the prognostic impact of abnormalities has increased substantially. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 2,902 patients.

Patients and methods: Patients were included from the German-Austrian MDS Study Group (n = 1,193), the International MDS Risk Analysis Workshop (n = 816), the Spanish Hematological Cytogenetics Working Group (n = 849), and the International Working Group on MDS Cytogenetics (n = 44) databases. Patients with primary MDS and oligoblastic acute myeloid leukemia (AML) after MDS treated with supportive care only were evaluated for overall survival (OS) and AML evolution. Internal validation by bootstrap analysis and external validation in an independent patient cohort were performed to confirm the results.

Results: In total, 19 cytogenetic categories were defined, providing clear prognostic classification in 91% of all patients. The abnormalities were classified into five prognostic subgroups (P < .001): very good (median OS, 61 months; hazard ratio [HR], 0.5; n = 81); good (49 months; HR, 1.0 [reference category]; n = 1,809); intermediate (26 months; HR, 1.6; n = 529); poor (16 months; HR, 2.6; n = 148); and very poor (6 months; HR, 4.2; n = 187). The internal and external validations confirmed the results of the score.

Conclusion: In conclusion, these data should contribute to the ongoing efforts to update the IPSS by refining the cytogenetic risk categories.

Fig 1.

(A) Overall survival (n = 1,893) and (B) risk of acute myeloid leukemia transformation (n = 1,691) in distinct cytogenetic subgroups (abnormalities with n < 10 combined as Any 1). Any 1, any other single abnormality; double 5, double abnormalities including del(5q); double, any other combination of two abnormalities; double 7, double abnormalities including −7/7q−; complex 3, three abnormalities; complex > 3, four or more abnormalities; + indicates P < .01 (as compared with reference category); (*) indicates P < .05 (as compared with reference category). Ind., independent.

Fig 2.

(A, B) Kaplan-Meier curves and (C, D) forest plots for (A, C) overall survival and (B, D) risk of acute myeloid leukemia (AML) transformation in new cytogenetic prognostic subgroups; + indicates P < .01 (as compared with reference category). 5-EV, external validation set (MD Anderson Cancer Center [MDA]), scaled, five groups; 5-T, test set, scaled, five groups; int, intermediate; IV, internal validation set; T, test set; val; validation.

Fig 3.

Change of cytogenetic prognostic subgroups in the new system as compared with the cytogenetic module of the International Prognostic Scoring System (IPSS).

Fig A2.

In (A, B) double and (C, D) complex abnormalities, (A, C) overall survival and (B, D) risk of acute myeloid leukemia (AML) transformation. Double 5, double abnormalities including del(5q); double, any other combination of two abnormalities; double 7, double abnormalities including −7/7q−; complex 3, three abnormalities; complex > 3, four or more abnormalities.

Fig A3.

(A) Overall survival and (B) risk of acute myeloid leukemia (AML) transformation in patients with deletion 7q as compared with those with total monosomy 7.

Fig A1.

Overall survival (OS) by date of first diagnosis.

Fig A4.

MD Anderson Cancer Center validation results (univariate analysis) regarding (A) overall survival and (B) risk of acute myeloid leukemia (AML) transformation. HR, hazard ratio.