Recovery of spermatogenesis after total-body irradiation.

criteria and 40% in the best schedule (5-day intravenous). This compares favorably with prior experiences with decitabine and 5-azacitidine (CR rates, 6%-20%).4,5 Also, decitabine was less toxic than 5-azacitidine in relation to nausea/vomiting and local skin reactions (pain and induration in 5%-10% of patients on 5-azacitidine). The incidence of 65% of hospitalization is cumulative. As one delivers more courses of effective therapy, the probability of a 1-time hospitalization would be more likely after multiple courses than after 1 or 2 courses. In the summary briefing of the Food and Drug Administration (FDA) by Kaminskas et al,6 the incidence of serious adverse events (mostly febrile episodes and hospitalizations) was 60%, similar to our experience. Thus, short of directly comparative trials, the current studies suggest that at the current dose schedules, decitabine and 5-azacitidine are probably equally myelosuppressive. The paper makes no comments on the relationship between p15 methylation and expression. In fact, analysis of the data shows that samples in which p15 methylation was greater than 15% had 6-fold lower expression of p15 than unmethylated samples, exactly as expected7 (deltaCT compared with GAPDH, 21.7 in the methylated group, and 19.2 in the unmethylated group; P .001). No patients with a high degree of methylation had high levels of expression. However, a low degree of methylation was not necessarily predictive of high-level expression, suggesting that factors other than methylation are also associated with p15 down-regulation in MDS. It is interesting to note that few patients in this study had high levels of p15 methylation. Thus, the p15 induction by decitabine observed came from both p15 hypomethylation-related and -unrelated epigenetic effects. It is also well known that DNA methylation inhibitors can affect gene expression independent of promoter methylation.8 We agree that the results we observed may be confounded by the presence of lymphocytes. Unfortunately, no sorted samples are available from these patients to address this issue experimentally. Unpublished data from our laboratory (Y.O. and J.-P.I., 2006) showing a high degree of correlation between methylation in unsorted peripheral blood mononuclear cells and unsorted bone marrow mononuclear cells suggest that variable contamination with nonmalignant lymphocytes is unlikely to be significant. This issue clearly should be tested in future studies. We hope this clarifies the points raised. Based on our experience, decitabine appears to be the most active anti-MDS single agent. Further experience with single-agent decitabine and with decitabine combinations may hopefully improve prognosis in MDS and CMML.