Background: High dose chemotherapy with ASCR is a key component of therapy for patients (pts) with HRNB, but the optimal ASCR regimen is not defined. CEM is the current US standard; however, European data suggest that BuMel may improve outcomes with less toxicity. Published data regarding toxicities associated with CEM and BuMel within current-era HRNB therapy are limited. Methods: Pts with HRNB who underwent single ASCR with CEM or BuMel from 6/1/10-6/30/13 were identified in the Pediatric Health Information System (PHIS) database. RU data for 60 days (d) from the start of BuMel or CEM were compared using a Wilcoxon 2-sample test. A retrospective chart review of contemporaneously treated pts was conducted at Children’s Hospital of Philadelphia (CHOP) to evaluate toxicities that could not be identified in PHIS, such as sinusoidal obstruction syndrome (SOS). Data were analyzed using Fisher’s exact test. Results: Total inpatient days were greater in the PHIS BuMel group (n=59) than in the CEM group (n=171; Table); there was no difference in ICU-level days. Total days of mechanical ventilation and diuretic use were higher after BuMel. Antibiotic and antihypertensive use was more frequent after CEM. There were no differences in opiate, parenteral nutrition, dialysis, or vasopressor days. In the CHOP cohort, 1/13 CEM (8%) and 5/21 (24%) BuMel pts developed SOS (p=0.37). Mean time from ASCR to SOS was 20d for BuMel and 13d for CEM. Pulmonary hypertension (PHTN) occurred only after BuMel (n=4; 19%). Nearly half of CEM pts (46%) and no BuMel pts developed creatinine ≥2x baseline (p=0.001). Time to engraftment and ASCR related mortality were similar. Conclusions: RU associated with pain control, nutrition, and ICU-level care was similar in HRNB pts receiving CEM and BuMel. CHOP data suggest that SOS and PHTN following BuMel may in part explain the longer hospital stays of BuMel pts. Evaluation of SOS in a larger cohort of BuMel pts is needed. Monitoring for PHTN after BuMel may be warranted.