Welch et al. (Nov. 24 issue)1 report the results of a study in which they treated 116 patients, including 26 with myelodysplastic syndromes (MDS), with a 10-day regimen of decitabine in monthly cycles and reported high rates of morphologic remission among patients with TP53 mutations. Although we agree that current data support the use of hypomethylating agents, including decitabine and azacitidine, for patients with complex cytogenetic abnormalities and TP53 mutations, we disagree with the authors’ conclusion that TP53 mutations specifically confer increased rates of response to decitabine and that a 10-day regimen is required to obtain such responses. We base our opinion on a review of four previous studies (Table 1Table 1Outcomes of Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes (MDS) Treated with Hypomethylating Agents in Four Studies, According to TP53 Mutation Status.)2-5 evaluating the effect of TP53 mutations on the rates of overall and complete response to various regimens of hypomethylating agents. In these studies, patients with TP53 mutations had rates of response that were similar to, but not higher than, the rates among patients with wild-type TP53. Therefore, although current data indicate that TP53 mutations do not negate a response to hypomethylating agents, both decitabine and azacitidine induce responses. Randomized studies comparing a 5-day regimen versus a 10-day regimen of decitabine would confirm the need for a 10-day


Welch J, Petti AA, Ley T