CT-207 Protracted Diarrhea from High-Dose Melphalan in Autologous Hematopoietic Transplantation: Response to Short Course of Oral Budesonide

Abstract

Approximately, 40% of patients receiving high dose melphalan (HDM) develop grade III or IV diarrhea (CTCAE 5.0) that promptly improves upon neutrophilic engraftment. Persistence of grade III diarrhea beyond 72 hours post-engraftment, though uncommon results in significant morbidity and prolongs hospitalization. Enlighten by a histopathologic finding of crypt inflammation, we utilized a short course of oral budesonide in a patient resulting in rapid resolution of diarrhea. We herein document 3 such cases and discuss their role in reducing morbidity and duration of hospitalization. All patients (age 44, 63 and 65, 2 female) received melphalan 200 mg/m2. Neutrophilic engraftment occurred on day +11 in 2 patients and day +12 in 1. Persistent grade III diarrhea 72 hours after neutrophil engraftment is defined as protracted diarrhea from melphalan. Infectious workup included stool examination for salmonella, shigella, rotavirus, cryptosporidium, and clostridium difficile we negative. Colonoscopy in one patient confirmed patchy crypt apoptosis and crypt abscess formation. Standard supportive care including antidiarrheals offered no improvement. Oral budesonide (BUD)was introduced at 5, 7- and 16-days post-engraftment (day + 17, +18 and +27 of ASCT). The dose of BUD comprised 6 mg/day in 2 while one patient received a 9 mg/day dose. Two patients had rapid resolution of diarrhea within 48 hours, while the third patient improved in 7 days. Total duration of BUD was 2, 2, and 26 days. Patients received a total cumulative dose of 12 mg, 15 mg, and 117 mg. Time to discharge from BUD initiation was 2, 2, and 7 days. A translational model of melphalan-induced gut toxicity reveals drug-host-microbe interaction that drives tissue injury and inflammation. Palifermin, a recombinant human keratinocyte growth factor is effective in reducing diarrhea of HDM. However, its cost is prohibitive. While newer melphalan preparations are available and prevention of melphalan-induced GI toxicity is being studied (Uproleselan), a short course of oral budesonide provided rapid resolution and facilitated patient discharge. Oral BUD results in rapid resolution of lower GI toxicity of HDM and potentially lowers the cost of hospitalization.