Serum ferritin and ECOG performance status predict the response and improve the prognostic value of IPSS or IPSS-R in patients with high-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia treated with 5-azacytidine: a retrospective analysis of the Hellenic national registry of myelodysplastic and hypoplastic syndromes

Abstract

Background: 5-azacytidine (5-AZA) improves survival of patients with higher-risk myelodysplastic syndromes (MDSs) and oligoblastic acute myeloid leukemia (AML); however, predictive factors for response and outcome have not been consistently studied.

Methods: This study of the Hellenic MDS Study Group included 687 consecutive patients with higher-risk MDS and oligoblastic AML treated with 5-AZA.

Results: The International Prognostic Scoring System (IPSS) revised version (IPSS-R), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 or 1 versus ⩾2) and baseline serum ferritin (SF) levels > 520 ng/ml were shown to independently predict response to 5-AZA. In the survival analysis, the IPSS and IPSS-R risk classification systems along with the ECOG PS and SF levels > 520 ng/ml proved to be independent prognosticators for overall survival (OS), as well as for leukemia-free survival (LFS). Next, we built new multivariate models for OS and LFS, incorporating only ECOG PS and SF levels besides IPSS or IPSS-R risk classification systems. Thereby, the new modified IPSS and IPSS-R risk classification systems (H-PSS, H-PSS-R) could each discriminate a low, an intermediate and a high-risk patient group regarding OS and LFS. The H-PSS and H-PSS-R proved to be better predictors of OS than their previous counterparts as well as the French prognostic score, while the most powerful OS predictor was the new, H-PSS-R system.

Conclusions: ECOG PS and SF levels > 520 ng/ml independently predict response to 5-AZA, OS and LFS. Their incorporation in the IPSS and IPSS-R scores enhances these scores' predictive power in 5-AZA-treated higher-risk MDS and oligoblastic AML patients.

Keywords: acute myeloid leukemia; outcome; prognosis; risk classification system; survival.

Figure 1.

Kaplan–Meier OS and LFS curves, showing the prognostic significance of ECOG PS and SF levels in patients with higher-risk myelodysplastic syndromes and oligoblastic AML, treated with 5-azacytidine. Poor ECOG PS (⩾2) and high SF levels (⩾520 ng/ml) predict unfavorable [(a) and (b), respectively] and inferior LFS [(c) and (d), respectively]. Total number of patients of each cohort and number of events are shown. ECOG PS, Eastern Cooperative Oncology Group Performance Status; LFS, leukemia-free survival; OS, overall survival; SF, serum ferritin.

Figure 2.

Kaplan–Meier survival curves, showing the prognostic significance of H-PSS and H-PSS-R risk classification systems in patients with higher-risk myelodysplastic syndromes and oligoblastic AML, treated with 5-azacytidine. Both H-PSS and H-PSS-R have very high prognostic significance, with regard to OS [(a) and (b), respectively] and LFS [(c) and (d), respectively]. Total number of patients of each cohort and number of events are shown. AML, acute myeloid leukemia; H-PSS, modified International Prognostic Scoring System risk classification system; H-PSS-R, modified International Prognostic Scoring System (revised) risk classification system; LFS, leukemia-free survival; OS, overall survival.