Azacitidin Is Effective in the Therapy Related Myelodysplastic Syndrome.
Authors: Yamauchi Hirofumi , Yokoyama Masahiro , Mishima Yuko , Nishimura Noriko , Ueda Kyoko , Kusano Yoshiharu , Inoue Norihito , Takahashi Anna , Terui Yasuhito , Hatake Kiyohiko 
Published: October 2019

Abstract
Introduction:
Myelodysplastic syndromes (MDS) are clonal hematopoietic neoplasms characterized by abnormal maturation of precursor cells which often translates into peripheral blood cytopenias and a high rate of transformation to acute myeloid leukemia (AML) due to accumulation of genetic alterations.
The AZA-001 trial showed azacitidine (AZA) significantly prolonged median overall survival compared with conventional care regimens (24.5 vs 15.0 months; P=0.0001).
AZA is standard first-line treatment for Intermediate-2 and High-risk myelodysplastic syndrome patients who are not immediate candidates for allogeneic stem cell transplantation, but this study included no cases of therapy related MDS (t-MDS).
T-MDS is known to have poor prognosis, therefore it is very important to analyze the outcome of patients with t-MDS treated in the front-line with AZA.
Methods: We studied newly diagnosed 29 MDS patients who were treated by AZA in our hospital from July, 2010 to April, 2016, retrospectively. AZA was given subcutaneously at 75 mg/㎡per day for 5 or 7 days every 28 days.
Results: We analyzed 29 MDS patients. According to the WHO classification, there were 12 RA, 15 RCMD, 10 RAEB-1, 2 RAEB 2 and 1 MDS-U. The median age was 70 year (range 49-88), and men was 12 (41.3%). There were 12 de novoMDS cases (41.3%) and 17 t-MDS cases (58.6%). All of the t-MDS patients had previously received chemotherapy (17 patients, 100%) and 9 patients had also received radiotherapy (9 patients, 53%).
Very poor risk group was 47.1% (9/17) in t-MDS group compared to 25.0% (3/12) in de novo MDS group (P=0.26).
Median follow up time was 11.4 months (range 1.4-47.8). Twenty five patients (86.3%) were treated by AZA for 5 days. Four patients (13.7%) were treated by AZA for 7 days, but all 4 patients decreased the dosing period to 5 days due to unacceptable toxicity. AZA was given for a median of 4 cycles (range 1-33).
In 29 MDS patients, 1-year overall survival (OS) was 60.5% (95% CI, 38.7-76.7%) and 1-year PFS was 40.1% (95% CI, 18.8-60.6%). After a median follow-up of 11.4 months, median OS was 18.7 months (95% CI, 9.4-21).
One-year OS was 59.3% in t-MDS group compared to 63.6% in de novo MDS group (P=0.294). 1-year PFS was 38.4% in t-MDS group compared to 40.4% in de novo MDS group (P=0.626).
One-year OS was 37.5% in very poor risk karyotype group (R-IPSS) compared to 74.6% in not very poor risk karyotype group (P=0.000748). 1-year PFS was 43.2% in very poor risk karyotype group compared to 39.0% in not very poor risk karyotype group (P=0.594).
Focusing on t-MDS group, 1-year OS was 46.9% in very poor risk karyotype group (8/17 47%) compared to 74.1% in not very poor risk karyotype group (9/17 53%) (P=0.054). 1-year PFS was 48.0% in very poor risk karyotype group compared to 26.0% in not very poor risk karyotype group (P=0.339).
Conclusions: In our study, 1-year OS in all MDS patients was 60.5%. It was slightly poor prognosis than 1-year OS in AZA-001 trial (about 70%).
Our study include t-MDS cases (58.6%). Additionally, AZA was given for a median of 4 cycles in our study but 6 cycles in the AZA-001 trial. It showed severe patient's background of our study. These difference may cause the lower median OS and poorer prognosis.
There trended to be more patients who had very poor risk karyotype in t-MDS group, but there was no significant difference between t-MDS and de novoMDS for the 1-year OS and PFS.
Azacitidin is effective in the therapy related myelodysplastic syndrome.

Disclosures
Yokoyama: Chugai: Consultancy. Mishima:Chugai: Consultancy. Nishimura:Chugai: Consultancy. Terui:Yanssen: Honoraria. Hatake:Kyowa Kirin: Honoraria, Research Funding; Chugai: Research Funding; Otsuka: Consultancy; Meiji-Seika: Consultancy.