Newly proposed therapy-related myelodysplastic syndrome prognostic score predicts significant differences in overall survival and leukemia-free survival in patients treated with azacitidine

Secondary (or therapy-related) acute myelogenous leukemia (t-AML) and myelodysplastic syndrome (t-MDS) have been reported after chemotherapy with alkylating agents and/ or topoisomerase inhibitors for the treatment of Hodgkin disease, non-Hodgkin lymphoma, breast cancer, ovarian carcinoma or testicular carcinoma [1,2]. Th ese disorders usually have a very poor prognosis with conventional chemotherapy, with an estimated overall survival (OS) of less than 1 year, due to the association with several negative features, such as older age, poor risk karyotype and resistance to chemotherapy [1 – 3]. Recently, we reported a retrospective analysis of 50 patients with therapy-related myeloid neoplasms (t-MN) treated with azacitidine with an overall response rate of 42% and a median OS of 21 months. We found that OS was signifi cantly better in patients with fewer than 20% of blasts, normal karyotype and in patients treated frontline with azacitidine [4]. Quintas-Cardama and colleagues [5] recently proposed a new score for patients with t-MDS, which was created in a large series of 279 patients with a history of previous exposure to chemo- or radiotherapy for prior malignancies. Th e model was able to identify diff erent OS based on the negative prognostic weight of several features at baseline (each one with 1 point), such as age higher than 65 years, Eastern Cooperative Oncology Group (ECOG) performance score higher than 1, monosomy 7 or complex karyotype, refractory anemia with ringed sideroblasts (RARS) or refractory anemia with excess blasts types 1 and 2 (RAEB1 – 2) according to the World Health Organization (WHO) classifi cation, hemoglobin level less than 11 g/dL, platelet count less than 50 10 9 /L and transfusion requirement. Patients were divided into three prognostic groups and subdivided into good risk (0 – 2 points), with a median OS of 34 months, intermediate (3 – 4 points), with a median OS of 12 months, and poor risk (5 – 7 points), with a median OS of 5 months. Th e model was tested in 189 patients with t-MDS with a median OS of 26, 13 and 7 months, respectively. Not all patients received azacitidine, and the subset of patients treated with this drug were not specifi cally reported. We retrospectively applied this score to our series of patients uniformly treated with azacitidine with the aim of validating the new proposed t-MDS score in this setting. We applied the score in 34 patients with t-MDS (12 refractory cytopenia with multilineage dysplasia [RCMD], nine RAEB-1 and 13 RAEB-2), with an overall response rate to azacitidine of 50%. Six patients had a low score (17%), 15 patients had an intermediate score (43%) and 14 patients had a poor score (40%). Among the good risk group, one patient achieved a complete remission (CR), one patient a partial response (PR), two patients a hematological improvement (HI) and two patients stable disease. On the other hand, among the intermediate risk group of patients, six achieved a CR, three a HI and fi ve stable disease, and within poor risk patients, eight had stable disease, two patients achieved a HI and one patient a CR, whereas three patients experienced disease progression after a median of four cycles. Median OS estimated with the Kaplan – Meier method according to the score stratifi cation for low, intermediate and poor risk patients was 17, 11 and 8.6 months, respectively ( p 0.02). Similarly, leukemia-free survival (LFS) was also signifi cantly diff erent in patients with low, intermediate and poor risk score (83%, 73% and 57%, respectively, p 0.01). Two out of six low risk patients (33%) died during treatment, compared to four of 14 (28%) intermediate risk and nine of 14 (64%) poor risk patients ( p 0.02).