Prognostic Significance of Severe Thrombocytopenia in Overall Survival of Patients with Myelodysplastic Syndromes Treated with Azacytidine. a Multicenter Study By the Hellenic MDS Study Group
Authors: Galanopoulos Athanasios , Kamouza Evdoxia , Kontos Christos K. , Symeonidis Argiris , Pappa Vassiliki , Kourakli Alexandra , Viniou Nora-Athina , Papageorgiou Sotirios , Pontikoglou Charalampos , Papoutselis Menelaos Konstantinos , Papadaki Helen A. , Hatzimichael Eleftheria , Zikos Panagiotis , Dimou Maria , Panayiotidis Panayiotis , Tsokanas Dimitrios , Mparmparousi Despina , Kontopidou Flora , Variami Eleni , Repousis Panagiotis , Poulakidas Elias , Christoulas Dimitrios , Vassilakopoulos Theodoros , Voulgarelis Michael , Megalakaki Aikaterini , Kotsopoulou Maria , Karianakis Giorgos , Kaliontzi Despina , Adamopoulos Ioannis , Dalekou Maria , Sioni Anastasia , Papaioannou Maria , Gogos Dimitrios , Diamantopoulos Panagiotis Theodorou , Solomou Elena E. , Kotsianidis Ioannis 
Published: October 2019

Abstract
INTRODUCTION: The hypomethylating agents 5-azacitidine (5-AZA) and decitabine are recently considered the most preferable treatment option for patients with intermediate-2 and high-risk myelodysplastic syndromes (MDS), by International Prognostic Scoring System (IPSS). 5-AZA responders experience improved survival both in clinical trials (AZA 001) and in the real-life setting. Thrombocytopenia is a common event in MDS, during the course of the disease; recently, severe thrombocytopenia (≤30,000 platelets/μL) has been suggested as an important factor regarding the survival of MDS patients. In the present study, we examined the potential prognostic significance of severe thrombocytopenia, in intermediate-2- and high-risk MDS patients, being treated with 5-AZA, during the first 3 years of treatment.
METHODS: This retrospective study included 850 higher-risk patients (intermediate-2- and high-risk), registered in the the Hellenic MDS Registry, treated with 5-AZA from 2010 to 2018 and were followed up for a time period up to 3 years. Complete patient data were available for 225 patients. Biostatistical analysis performed in this study included Kaplan-Meier survival analysis and Cox regression. The level of statistical significance was set at a probability value of less than 0.050 (P<0.050).
RESULTS: The current study included 225 patients (159 male and 66 women) with intermediate-2- or high-risk MDS treated with 5-AZA, with a median age of 74 years (range: 47 - 89). WHO diagnosis included 1 (0.4%) case of RCUD, 8 (3.6%) cases of RCMD, 3 (1.3%) cases of RCMD-RS, 43 (19.1%) cases of RAEB-1, and 170 (75.6%) cases of RAEB-2. According to IPSS, 174 (77.3%) patients were classified in the intermediate-2 risk group and 51 (22.7%) patients in the high-risk group. In addition, according to IPSS-R, 24 (10.7%) patients were categorized in the intermediate risk group, 106 (47.1%) patients in the high-risk group, and 95 (42.2%) patients in the very-high risk group. All patients were evaluated regarding response to 5-AZA treatment. The initial response at 6 months was: complete remission (CR) in 40 (18.4%) patients, partial remission (PR) in 24 (11.1%) patients, hematological improvement (HI) in 35 (16.1%) patients; therefore, the initial overall response rate (CR, PR, and HI) was 45.6%. Stable disease (SD) was achieved by 56 (25.8%) MDS patients, while 62 (28.5%) patients showed progression of disease (PD) or treatment failure. Severe thrombocytopenia was not predictive of response, as shown using logistic regression analysis. However, severe thrombocytopenia predicted poor overall survival (OS) in the first 3 years of treatment with 5-AZA, as shown by the Kaplan-Meier analysis (Figure 1; P=0.016). Regarding AML-free survival, a strong trend was observed for thy unfavorable prognostic role of this severe cytopenia (P=0.096). Univariate Cox regression analysis for OS revealed a statistically significant hazard ratio (HR) of 1.6 for MDS patients with severe thrombocytopenia (HR=1.6, 95% CI=1.08, P=0.019).
CONCLUSIONS: Our study showed that severe thrombocytopenia (≤ 30,000 platelets/μL) in intermediate-2- and high-risk MDS patients, treated with 5-AZA, predicts lower OS rates during the first 3 years of treatment.
Figure 1. Figure 1.

Disclosures
No relevant conflicts of interest to declare.