PB2087 PROGNOSTIC VALUE OF CLINICAL AND CYTOGENETIC PARAMETERS IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES TREATED WITH AZACITIDINE
Authors: Takahashi Y. , Tabayashi T. , Tanaka Y. , Kimura Y. , Tomikawa T. , Watanabe J. , Anan‐Nemoto T. , Sagawa M. , Nakaseko R. , Tokuhira M. , Kizaki M. 
Published: June 2019

Background:

Myelodysplastic syndromes (MDS) are characterized by cytopenia due to hematopoietic dysfunction and increased risk of transformation to acute myeloid leukemia. DNA hypomethylating agents such as azacitidine (AZA) significantly improve clinical outcomes in higher‐risk MDS and have become the standard therapy for this disease. However, prognostic factors for survival of patients with higher‐risk MDS treated with AZA remain largely unknown, and a prognostic scoring system for these patients in clinical practice has not been established. In addition, MDS occurs mainly in elderly patients, and cytotoxic drugs including AZA may cause frailty and impair quality of life. Therefore, identification of predictive factors related to response to AZA is needed.

Aims:

The goal of this retrospective study was to analyze a cohort of patients with higher‐risk MDS treated with AZA at a single institute.

Methods

Outcomes of 68 patients with higher‐risk MDS treated with AZA between April 2011 and October 2018 at Saitama Medical Center, Saitama Medical University, Kawagoe, Japan were evaluated retrospectively. AZA was administered at a dose of 75 mg/m2 for 5 days. The study was approved by our Institutional Review Board, and the procedures followed were in accordance with the Helsinki Declaration of 1975. Univariate and multivariate survival analyses were performed using Cox proportional hazards regression models. Overall survival (OS) was calculated from the date of initiation of AZA to the date of last follow‐up or death.

Results:

The median age was 70 years (range, 44‐86 years) and median OS was 14 months. The effects of cytogenetics, hemoglobin, neutrophil count, % circulating blasts, RBC transfusion dependency, serum albumin, IPSS‐R and WPSS on OS were examined. In univariate analysis, OS was significantly related to pretreatment low serum albumin (<3.7 g/dL) (HR = 2.56, 95% CI 1.35 to 5; p = 0.05), pretreatment low hemoglobin (<9 g/dL) (HR = 1.82, 95% CI 0.98 to 3.45; p = 0.057), and chromosome 7 deletion (HR = 2.29, 95% CI, 1.16 to 4.54; p = 0.018). In multivariate analysis, these three variables were shown to be independent prognostic factors for patients with MDS treated with AZA. We then classified the patients into three risk groups: low (score = 0), intermediate (score = 1), and high (score = 2 or 3), based on serum albumin (≥3.7 vs. <3.7 g/dL), hemoglobin (≥9 vs. <9 g/dL) and the presence or absence of deletion of chromosome 7. In evaluation of the prognostic value of this scoring system using a Cox regression proportional hazards model, patients in the three risk groups had significantly different OS (p<.0001). The median OS was 30 (range: 11‐49), 16 (14‐29), and 7 (3‐8) months in the low, intermediate, and high risk groups, respectively.

Summary/Conclusion:

Low serum albumin and low hemoglobin before treatment and deletion of chromosome 7 are independent unfavorable prognostic factors in patients with MDS treated with AZA. Our scoring system based on these factors provides a simple practical approach to predict outcomes of these patients in routine clinical practice.