Outcomes of MDS Patients with Chromosome 7 Abnormalities Treated with 5-Azacytidine.

Abstract Chromosome 7 abnormalities occurring in isolation or as part of complex cytogenetics confer an adverse prognosis in patients with myelodysplastic syndromes (MDS). Preliminary clinical data from various groups has suggested that the use of 5-azacytidine, a DNA methyl transferase inhibitor, in this sub-group of poor risk patients may be associated with an improved clinical response. We report on a retrospective analysis on the outcomes of 31 MDS patients with chromosome 7 abnormalities treated with 5-azacytidine. 5-azacytidine was administered subcutaneously at 75mg/m2 daily for 7 days and each cycle was repeated every 28 days. The median age of the cohort was 61 years (range: 17–80). Based on the WHO classification, 4 patients (13%) were RCMD/RCMD-RS, 17 were RAEB I/II (55%), 8 patients had acute myeloid leukemia transformed from MDS (26%), an additional 2 patients had secondary MDS. The IPSS of the cohort was Int-1(n=1), Int-2(n=12), high-risk(n=18). 13(42%) patients had isolated chromosome 7 abnormalities, 8(58%) had chromosome 7 abnormalities as part of a more complex cytogenetic profile. 10 patients(33%) had previously been treated prior to therapy with 5 azacytidine. 5 patients were withdrawn from treatment after 1 cycle due to drug intolerance or disease progression and were excluded from further analysis. The remaining 26 patients received a median of 6 cycles of treatment (range: 2–28 cycles). Response criteria was based on the modified IWG response criteria for MDS (Cheson et al Blood 2007). 7 patients achieved a complete response (CR), 3 partial response (PR), with haematological improvement (HI) in a further patient. The median cycles of treatment before response was 2, with median response duration of 10.5 months (range: 4–20 months). Overall response rate (CR+PR+HI) was 6/12 (50%) for patients with isolated chromosome 7 abnormalities as compared with 5/14 (36%) for patients with complex cytogenetics (p=0.15). 7 patients had a complete cytogenetic response, with a further 2 patients achieving a partial cytogenetic response. These cytogenetic responses were observed in 4/12 patients with isolated chromosome 7, and 5/16 patients with complex cytogenetics. The median survival of the cohort was 19.8 months (95%CI: 16.3–23.3). Patients with isolated chromosome 7 abnormalities had median survival of 24.8 months (95%CI: 17.8–31.8) compared with those with complex cytogenetics (17.3 months, 95%CI: 8.3–26.3, p=0.10). In addition, patients achieving cytogenetic remission (complete or partial) had an improved overall survival when compared with non-responders (median OS: 24.8 vs 19.8 months, p=0.05). WHO classification, IPSS, patient age, and history of prior therapy were all not significant predictors of response or overall survival in this cohort. In summary, 5-azacytidine is able to induce high remission rates in a cohort of high risk MDS patients with chromosome 7 abnormalities.