Abstract
Background:
High-dose melphalan (HDM) is commonly used for conditioning prior to autologous stem cell transplant (ASCT) in multiple myeloma and lymphoma. Gastrointestinal toxicity, particularly grade III-IV diarrhea, occurs in approximately 40% of patients and typically resolves after neutrophilic engraftment. However, persistent diarrhea beyond 24 hours post-engraftment significantly contributes to morbidity, delayed discharge, and increased healthcare utilization. Effective therapies targeting post-engraftment lower GI mucositis are lacking.
Aims:
To evaluate the safety and efficacy of a short course of oral budesonide (BUD) in resolving persistent diarrhea attributed to melphalan-induced intestinal mucositis in post-ASCT patients.
Methods:
A retrospective case series of 20 adult patients who developed persistent grade III-IV diarrhea ≥24 hours after neutrophil engraftment following ASCT with HDM-based conditioning. Infectious workups including stool testing for Clostridium difficile, Salmonella, Shigella, rotavirus, and Cryptosporidium were negative in all included cases. Colonoscopy in one index patient demonstrated patchy crypt apoptosis and crypt abscesses. Budesonide (3–9 mg/day) was initiated at a median of 2 days (range, −4 to +11) post-engraftment in 14 patients; 6 received BUD pre-engraftment based on established safety. Response was defined as time to improvement and resolution of diarrhea.
Results:
Median patient age was 66 years (range, 44–74), with equal sex distribution. See table 1. Diagnoses included multiple myeloma (n=14), diffuse large B-cell lymphoma (n=4), Hodgkin lymphoma (n=1), and acute lymphoblastic leukemia (n=1). Melphalan doses were 200 mg/m² (n=10) or 140 mg/m² (n=10; due to age or renal impairment). Median engraftment occurred on day +12 (range, +9 to +13). Median time to improvement in diarrhea after BUD initiation was 1 day (range, 1–7), and the median duration of BUD administration was 2 days (range, 1–13). Median time to hospital discharge from BUD initiation was 2 days (range, 1–7). No adverse events attributable to BUD were observed. One patient with rotavirus (excluded from efficacy analysis) also showed rapid improvement post-BUD. The median cumulative BUD dose was 18 mg (range, 9–60 mg).
Summary/Conclusions:
Short-course oral budesonide appears to be a safe and effective strategy for the rapid resolution of persistent post-engraftment diarrhea due to melphalan-induced intestinal mucositis. Initiation of BUD facilitated early discharge and reduced morbidity without observable adverse effects. Larger prospective studies are warranted to validate these findings.
