Adolescent and young adult patients with acute lymphoblastic leukemia (ALL) have superior outcomes when treated on pediatric regimens. Pediatric ALL regimens rely heavily on corticosteroids and asparaginase and are known to increase the risk of osteonecrosis (ON) and fractures in children, particularly adolescents. Orthopedic toxicity among young adults treated on pediatric-inspired regimens is not well described. Here, we report the symptomatic orthopedic toxicities of patients aged 15-50 years treated on sequential Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols. Among 367 patients with a median age of 23 years (range 15-50, 68% < 30 years), 60 patients were diagnosed with ON (5-year cumulative incidence (CI) 17%; [95% confidence interval 13-22]) and 40 patients experienced fracture (5-year CI 12% [95% CI 8-15]). Patients < 30 years were significantly more likely to be diagnosed with ON (5-year CI 21% vs. 8%, p=0.004). Patients treated more recently on pegaspargase-based protocols were significantly more likely to be diagnosed with ON compared to those treated on earlier trials with native E.coli asparaginase (5-year CI 24% vs 5%, p<0.001). Of the 54 ON events for which adequate information was available, surgery was performed in 25 (46%). Patients with ON had superior overall survival (OS) compared to those without (multivariable OS HR 0.15 [95% CI: 0.05-0.46], p=0.001; ON included as a time-varying exposure). Increased rates of orthopedic toxicity in late generation protocols may be driven by the pharmacokinetic drug interaction between pegaspargase and dexamethasone, leading to higher dexamethasone exposure.

Background: The manufacture and sale of natural products constitute a multi-billion dollar industry. Nearly a third of the American population admit to using some form of complementary or alternative medicine, with many using them in addition to prescription medications. Most patients fail to inform their healthcare providers of their natural product use and physicians rarely inquire. Annually, thousands of natural product-induced adverse events are reported to Poison Control Centers nationwide. Natural product manufacturers are not responsible for proving safety and efficacy, as the FDA does not regulate them. However, concerns exist surrounding the safety of natural products. Summary: This review provides details on natural products that have been associated with renal dysfunction. We have focused on products that have been associated with direct renal injury, immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, hepatorenal syndrome, and common adulterants or contaminants that are associated with renal dysfunction. Key Messages: The potential for natural products to cause renal dysfunction is justifiable. It is imperative that natural product use be monitored closely in all patients. Healthcare practitioners must play an active role in identifying patients using natural products and provide appropriate patient education.

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Hepatic veno-occlusive disease or sinusoidal obstructive syndrome (VOD/SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Defibrotide is the only medication approved by the US Food and Drug Administration for the management of severe VOD/SOS after HSCT. We report our center’s experience with commercially available defibrotide as treatment of patients with VOD/SOS. We retrospectively identified 28 cases of VOD/SOS, based on the European Society for Blood and Marrow Transplantation criteria, from March 2016 through June 2019. The median day of VOD/SOS onset was 25 days (range, 8-69 days), and defibrotide was initiated on day of diagnosis in 71% of patients. Complete resolution of VOD/SOS occurred in 75% of patients. Day 100 survival was 64% for all HSCT patients and 53% for those with very severe VOD/SOS. Response rates and survival were similar in patients with VOD/SOS after myeloablative or reduced-intensity chemotherapy HSCT. Therapy-related adverse events were mild and included hematuria (43%), epistaxis (18%), and hypotension (11%). Severe hemorrhagic adverse events occurred in 2 patients (pulmonary hemorrhage and upper gastrointestinal hemorrhage; 7%) and both in the setting of progressive VOD/SOS. Early diagnosis, prompt initiation of defibrotide, and minimization of dosing interruptions may be key to successful treatment of VOD/SOS.