Pb2463: protracted diarrhea from high-dose melphalan in autologous hematopoietic transplantation: response to short course of oral budesonide

Topic: 22. Stem cell transplantation - Clinical Background: Approximately, 40% 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 24 hours post engraftment, though uncommon results in significant morbidity and prolongs hospitalization. Aims: To Explore role of oral Budesonide for patients with persistent diarrhea following high dose melphalan based chemotherapy conditioning Methods: Histopathologic finding of colonic crypt inflammation in a patient (first on table 1) led to utilization of short course of oral budesonide (BUD) resulting in rapid and sustained resolution of diarrhea. We herein document 5 such cases and discuss its role in reducing morbidity and duration of hospitalization. Persistent grade III diarrhea 24 hours after neutrophil engraftment defined protracted diarrhea from melphalan. Infectious workup including stool examination for salmonella, shigella, rotavirus, cryptosporidium, clostridium difficile were performed. Results: The median age of 5 patients was 64 (range, 44-73) years (Females=3, Males=2). A total of 3 patients with multiple myeloma received melphalan 200 mg/m2 while 1 with associated renal failure received Melphalan 140 mg/m2. One patient with Hodgkin’s lymphoma also received melphalan 140 mg/m2 (table 1). Median time to neutrophilic engraftment following autologous stem cell transplant (ASCT) was day +12 (range, 10-12) days. 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 median of 2 (range, 1-11) days from engraftment. The median cumulative dose of BUD comprised 12 mg (range, 9-72 mg). Four patients had rapid resolution of diarrhea within 24 hours, while 5th patient improved in 7 days. Median duration of BUD was 2 (range, 1-7) days. Median time to discharge from BUD initiation was 2 days (range 1-7). An additional patient was excluded from analysis as his stool tested positive for rotavirus; he too promptly responded to BUD. Summary/Conclusion: In absence of systemic studies, we postulate that reduction in gut inflammation improves diarrhea. We do not think these diarrheas were related to autologous graft versus host disease. We did not observe any untoward effects of such short courses of BUD. Palifermin, a recombinant human keratinocyte growth factor is effective in reducing diarrhea of HDM. However, its cost is prohibitive. Oral BUD results in rapid resolution of lower GI toxicity of HDM and potentially lowers cost of hospitalization.Keywords: Autologous hematopoietic stem cell transplantation