Reply to R. Lakhotia et al

Abstract

We thank Lakhotia et al 1 for their interest in our article. 2 Their opening comment that dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) did not improve event-free survival (EFS) compared with historical controls treated with rituximab plus pediatric chemotherapy regimens is unfortunately incorrect as the historical controls for our study were all treated without rituximab. We have discussed this in our Discussion and suggested that DA-EPOCH without rituximab may be less effective than the historical pediatric regimens. 2 Lakhotia et al 1 raised the important point of dose intensity as a determinant of outcome in lymphoma and hypothesized that our finding of errors in dose escalation in at least one course in 29% of patients led to the observed lack of improvement with DA-EPOCH-R. Although this is certainly a plausible hypothesis, we do not think this is applicable for two main reasons. First, appropriately designed randomized trials are required to determine the impact of dose intensity on outcome for patients treated for non-Hodgkin lymphoma, 3 and to our knowledge, there has not been such a study for DA-EPOCH-R in primary mediastinal large B-cell lymphoma (PMLBL). Second, delivered dose intensity and its impact on outcome of DA-EPOCH-R have not been reported to date in any other study to our knowledge and so we do not agree that it is reasonable to suppose that the failures to escalate in at least one dose that we have reported contributed to the performance of DA-EPOCH that we observed. In addition, the EFS of patients correctly escalated in our study was 76.7% (95% CI, 59.1 to 88.2) which was inferior to that expected based on the National Cancer Institute (NCI) study, suggesting that factors other than dose intensity account for the poorer performance of DA-EPOCH-R in the pediatric setting.