Oral Beclomethasone Dipropionate Monotherapy as An Initial Treatment for Stage 1-2 Gastrointestinal Tract Acute Graft-Versus-Host Disease Following Unrelated Cord Blood Transplantation.

Systemic corticosteroid has been used as initial treatment for gastrointestinal tract acute graft-versus-host disease (GI-aGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, the response remains far from satisfactory, and adverse events caused by prolonged immunosuppression are significant problem. Oral beclomethasone dipropionate (BDP) is a topically active corticosteroid with low bioavailability. Although several studies demonstrated that BDP as monotherapy or in combination with systemic corticosteroid is safe and effective for treatment of GI-aGVHD, there has been not much data available regarding this issue in unrelated cord transplantation (UCBT). Design and

This study was approved by the institutional review board and started since January 2006. BDP was administered as a single agent in patients who developed stage 1-2 GI-aGVHD following UCBT, were able to swallow the drug, and gave written informed consent. BDP was administered orally as one enteric-coated cellulose capsule and an aqueous suspension every 6h for a total daily dose of 8mg. Response was evaluated on days 3, 7, 14, 21, and 28 after the beginning of BDP treatment. Patients who had worsening GI symptoms at day 3, or who had no improvement at day 7 were classified as nonresponders, and systemic corticosteroid was started.

Forty patients were included in this analysis from Jan 2006 through April 2009. Median age was 53.5 years (range 22-82). Twenty-eight (70%) had advanced disease (relapse or refractory disease), and 12 (30%) had history of prior transplantation. All but one patient received fludarabine-based preparative regimen. GVHD prophylaxis consisted of tacrolimus plus mycophenolate mofetil in 27, and tacrolimus alone in 13. Single cord blood units, matched at 4/6 in 35, 5/6 in 3, and 6/6 in 2, were infused. GI-aGVHD developed at a median of 32.5 days (range, 8-80 days) post-transplant. Twenty-five (62.5%) had stage 1 and 15 had stage 2 GI-aGVHD. Twenty (50%) had only GI involvement and the others had mild skin involvement. BDP was started at a median of 36 days (range, 8-86 days) post-transplant. Thirty-three (82.5%) responded to BDP treatment. Response occurred at a median of 4 days (range, 2-7 days) after BDP treatment. Response rate was suggestively higher in patients with stage 1 GI-aGVHD (88%) compared with those with stage 2 (73%), although not statistically significant (P=0.1). The median duration of BDP treatment was for 51 days (range, 7-343 days). Three patients progressed and 4 patients did not respond. Twenty-seven (67.5%) developed infectious episodes during BDP treatment; bacterial sepsis in 9, CMV reactivation in 10, CMV gastroenteritis in 2, Fungal pneumonia in 3, and others in 3 patients. Two patients developed symptomatic adrenal insufficiency during BDP treatment, and required systemic steroid hormone replacement. Transplant-related mortality was 15% at 100 days post-transplant. Three patients died due to sepsis associated with GVHD, 2 died from idiopathic pneumonia syndrome, and 1 died from invasive fungal infection. At median follow-up of 475 days (range, 132-1368 days), overall survival at 2 years was 35.7%. Conclusions: In this study, we evaluated the efficacy and safety of BDP as a single agent in a series of patients with stage 1-2 GI-aGVHD following UCBT. The response rate was 82.5%, which compares favorably with previously reported response rate using BDP as monotherapy or in combination with systemic corticosteroid after allogeneic HSCT. Furthermore, BDP treatment was not associated with the increased risk of severe opportunistic infections. We conclude that BDP as a single agent could become an ideal therapeutic approach for stage 1-2 GI-aGVHD following UCBT

No relevant conflicts of interest to declare.