Be ever cautious until the truth is proven
Authors: Sylvain Chantepie, Ibrahim Yakoub‐Agha, Gandhi Damaj
Journal: American Journal of Hematology (2019)

We would like to thank Dr. Isidori et al1 for their interest in our study.2 We do agree that the best way to come to a definitive conclusion for a conditioning regimen—the focus of our article—is a prospective and randomized trial. Unfortunately, over the last decades, the medical community has not been able to perform this kind of trial in either the autologous or the allogeneic stem cell transplant setting and instead we were satisfied by a small and heterogeneous phase II studies. Bendamustine is effective in lymphoproliferative disease. Its role as conditioning regimen has emerged, after the shortage of carmustine, based on the first and small report by Visani et al. (n = 43 patients; 9 in phase 1, 34 in phase 2).3 Isidori et al questioned the quantity of fluid hydration, in our study, stating that more than 200 patients would have received less than 3 L per day. Despite some caveat related to the retrospective nature of our study, we all know that hydration volume depends on local guidelines. It is worth mentioning that we found no data regarding hydration characteristics and the real hydration volume administered to patients in the Visani et al. study. Hydration data are also lacking in the two following prospective studies: Noesslinger et al. (n = 41 patients)4 and Gilli et al. (n = 39 patients).5 As a matter of fact, hydration is usually based on center-specific practices and has never, even in prospective protocols, been investigated. In contrast to the above-mentioned studies, our study takes into account detailed characteristics of hydration protocols used (total volume, rate of administration, and number of days on hyperhydration), disease characteristics, and treatment parameters, all collected meticulously from medical files. Therefore, we believe that our data describe the real-life use of bendamustine outside clinical trial settings. In addition, by neither selecting patients nor implementing exclusion criteria, our study, in an effort to reflect current daily practices, includes a statistically significant and comprehensive sample of patients. Regarding intensice care unit (ICU), the rate of admission can vary from center to center according to local guidelines. Furthermore, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) encourages centers to refer their patients to ICU early, in order to optimize their care and to reduce mortality.6 The assumption of the authors on the high ICU admission rate is not supported by literature reports and is based on their personal communication and unpublished data. ICU admission rate data are scarce and even nonexistent in autologous SCT settings. The rate of ICU admission that our study observes (10.3%) is in line with what Garciaz et al.7 and Gilli et al.5 have reported. While post-transplant toxicity-related mortality (TRM) is an objective parameter for toxicity. The TRM rate in our study was 3.3%, which holds consistent with what others have observed and reported. Thus, until a randomized study comparing BeEAM vs other conditioning regimens (mostly BEAM) was conducted, we cannot, in good faith, recommend BeEAM as standard conditioning regimen and felt it should be used with caution. Nothing to report.