Myelosuppression in myelodysplastic syndromes (MDS) is associated with the hypomethylating agent decitabine. had faster progression to AML versus patients with dose modifications (= .004). Without dose modifications patients tended to drop out due to disease progression or other reasons. Decitabine dose modifications on treatment may indicate response to treatment. = .013). Patients with cycle delays or dose reductions received a median of 6 cycles of decitabine compared with those without cycle delays or dose reductions who received a median of 2 cycles of decitabine. Adverse events disease progression lost to follow-up patient choice and investigator decision were the main reasons given for patients discontinuing therapy. Table II Patients receiving decitabine who had myelosuppression and required dose modifications In both studies measurement of hematologic values (hemoglobin lymphocytes neutrophils platelets and white blood cells) over time showed that the incidence of grade 3 or 4 4 toxicities was highest in cycle 1 of decitabine therapy then generally decreased over time with subsequent cycles although all were frequent events likely a result of the underlying disease. The nadir in hematologic values in cycle 1 was expected from the known myelosuppressive effects of decitabine and the improvement in Gata1 mean nadir over successive cycles suggests an absence of cumulative hematologic toxicity. Effects of Dose Modifications on Response Patients who had dose modifications patients who had cycle delays or dose reductions and patients who had cycle delays had significantly higher ORRs compared with those who had none of these (≤ .015) (Table III). Table III Overall response rate for patients receiving decitabine by subgroups with or without dose modifications There was no significant difference in time to OSI-906 initial dose modification between responding and nonresponding patients. The median time for responders was 2.07 months and the median for nonresponders was OSI-906 2.10 months. Effects of Dose Modifications on Survival Patients who had dose modifications (Figure 1) and patients who had cycle delays or dose reductions (Figure 2) had median OS values similar to those of patients who had neither. Median OS was 16.1 months in patients who had dose modifications and 16.3 months in those who had cycle delays and/or dose reductions compared with 15.3 months and 15.2 months respectively in patients who had neither dose modifications nor cycle delays or dose reductions. Figure 1 Kaplan-Meier curves for overall survival in patients receiving decitabine with and without dose modifications adjusted for a time-dependent covariate Figure 2 Kaplan-Meier curves for overall survival in patients receiving decitabine with and without dose delays or dose reductions adjusted for a time-dependent covariate Effects of Dose Modification on Transformation to AML Of the 182 patients in the pooled analysis 46 (25.3%) underwent transformation to AML. No significant differences were observed in time to AML transformation between patients with and without dose modifications (Figure 3A) and between patients with and without dose delays or dose reductions (Figure 3B). Figure 3 Kaplan-Meier curves for time to AML progression in patients receiving decitabine: (A) with and without dose modifications and (B) with and without dose delays or dose reductions adjusted for a time-dependent covariate Predictors of Dose OSI-906 Modifications and Death Cox regression analysis including baseline covariates and time-dependent covariates identified several OSI-906 predictors of decitabine dose modification and death (Table IV). Platelet dependence at baseline was a significant predictor for dose modification (= .006) dose reduction or delay OSI-906 (= .011) and death (= .003). Study effect (DACO-020 5 regimen) was also a significant predictor for dose modification and dose reduction or delay (< .0001 in both cases). In addition IPSS-1 (= .002) and red blood cell dependence at baseline (= .0001) were also significant predictors for death. Table IV Predictors of dose modification dose reduction or delay progression OSI-906 to AML or death DISCUSSION The findings of this retrospective analysis of a pooled subset of data from patients with MDS enrolled in 2 clinical trials of decitabine suggest that the effects of decitabine dose modification or cycle delay or dose reduction may be beneficial for decitabine response although no significant effect on patient survival was found. In the pooled analysis dose modifications cycle delays or dose reductions and.