Bendamustine‐based conditioning prior to autologous stem cell transplantation is associated with high rate of febrile neutropenia and higher mortality
Authors: Marko Lucijanic, Zeljko Prka, Ozren Jaksic, Zdravko Mitrovic, Anamarija Vrkljan, Vlatko Pejsa
Journal: American Journal of Hematology (2018)

We have read the article by Chantepie et al1 evaluating safety of benadamustine-based conditioning prior to autologous stem cell transplantation (ASCT) with great interest. The authors reported concerningly high frequency of acute renal failure (27.9%) and high rates of other toxicities observed with BeEAM (bendamustine, etoposide, cytarabine, melphalan) conditioning regimen. Shortage of carmustine led to replacement of standard BEAM (carmustine, etoposide, cytarabine, melphalan) with BeEAM conditioning regimen in our institution as well. High frequency of febrile netropenia and increased mortality that we observed prompted us to further compare toxicities and outcomes between these two regimens which we report here. We retrospectively analyzed a cohort of 60 ASCT patients 18 years or above with histologically confirmed diagnosis of Non-Hodgkin or Hodgkin lymphoma that received either BEAM (43 patients) or BeEAM myeloablative regimen (17 patients) as a part of the ASCT procedure in the period from 2008 to 2018. Bendamustine doses of 200 mg−1m−2day−1 were used. Acute kidney injury was defined according to KDIGO guidelines as in the article by Chantepie et al.1 Numerical variables were expressed as median and interquartile range (IQR) and were compared between two groups using the Mann–Whitney U test. Categorical variables were expressed as percentages and were compared between two groups using the Fisher test or χ2 test where appropriate. Survival analysis was based on the Kaplan–Meier method, the Cox–Mantel version of the log-rank test was used to compare survival between two groups. P values <0.05 were considered statistically significant. Analyses were done using the MedCalc statistical program ver. 18.10 (MedCalc Software bvba, Ostend, Belgium). Median age was 51.5 years, a majority of patients had diffused large B-cell lymphoma (53%). Patients' characteristics and outcomes are shown in Table 1. BEAM and BeEAM groups did not differ regarding age, gender, diagnosis, baseline-estimated creatinine clearance, duration of hospitalization, time to neutrophil or platelet recovery (P > 0.05 for all comparisons) showing that two regimens were comparable in terms of baseline and engraftment characteristics. However, patients receiving bendamustine were significantly more likely to develop acute kidney injury (23.5% vs 0% for BeEAM vs BEAM, respectively; P = 0.005), virtually all experienced febrile neutropenia (100% vs 74% for BeEAM vs BEAM, respectively; P = 0.025) and were more likely to require intensive care unit (ICU) management (23.5% vs 0% for BeEAM vs BEAM, respectively; P = 0.005). Most worrisome, patients receiving bendamustine experienced significantly higher 100-day mortality (17.6% vs 0% for BeEAM vs BEAM, respectively; P = 0.004) as shown in Figure 1. All three deaths observed in the bendamustine group were due to septic complications. It should be noted that high rates of ICU admission (24%) and renal toxicity (17%) were observed with BeEAM by other author groups as well.2 Although limited by small numbers, retrospective design and single center experience, our findings complement previously reported results by Chantepie et al, and raise serious concerns about safety of benadmustine-based conditioning prior to ASCT. We resorted to alternative conditioning regimen based on lomustine (LEAM-lomustine, etoposide, cytarabine, melphalan) until additional evidence regarding efficacy/safety of currently available regimens or new treatment options emerge. All authors declare they have no conflict of interest.