Hypomethylating Therapy in Patients with AML and High-Risk MDS and Chromosome 5 and 7 Abnormalities Is Associated with An Improved Outcome Compared to Conventional Chemotherapy

Outcome of patients with AML and high-risk MDS with chromosome 5 and 7 abnormalities [excluding del 5(q)] has been poor with fewer than 10% of patients alive at 2 years. We investigated whether the use of hypomethylating agents, 5-azacytidine and decitabine, is associated with an improved outcome. Between January 2004 and December 2007, a total of 81 pts [including 37 (46%) with AML (≥ 20% blast) and 44 (54%) with high-risk MDS] with chromosome 5 and 7 abnormalities were treated with hypomethylating agents as their initial therapy. This included 68 patients with complex abnormalities and 13 with less than 3 aberrations. During the same period, 151 patients (126 AML, 25 MDS) with chromosome 5 and 7 abnormalities (128 complex, 23 noncomplex) were treated with intensive cytotoxic chemotherapy (including cytarabine based regimens in 72% and other regimens in 28%). The median age for the two groups was 66 and 61 years, respectively [(ranges (37–85) and (19–89)]. Thirty three (41%) pts in the hypomethylating group achieved CR versus 53 (35%) pts in the chemotherapy group (p=0.395). With a median follow up of 51 weeks (range 12–101) and 40 weeks (range, 5–128), 22/33 pts in the hypomethylating group and 33/53 pts in the chemotherapy group have relapsed giving median CR duration of 45 weeks for the hypomethylating group and 23 weeks for the chemotherapy group (p=0.153). The overall survival was superior for the hypomethylating group as compared to the chemotherapy group (Figure). We conclude that treatment with hypomethylating agents may be superior to chemotherapy in patients with chromosome 5 and 7 abnormalities who are traditionally resistant to cytotoxic agents.

View largeDownload slide

Figure

View largeDownload slide

Figure

Close modal