Oral Beclomethasone Dipropionate for the Treatment of Gastrointestinal Chronic Graft-versus-Host Disease

Abstract

The most common approach for the treatment of chronic graft-versus-host disease (cGVHD) has been the long-term use of systemic steroids. Beclomethasone dipropionate (BDP) is a topically active corticosteroid with relatively low absorption from the gastrointestinal mucosa. It has been successfully used to treat acute GVHD (aGVHD), but its use in the cGVHD setting is far more limited. In the current study, BDP was administered to 33 patients who underwent allogeneic transplantation and had biopsy-proven gastrointestinal cGVHD (GI cGVHD). Twenty-six patients with GI cGVHD received BDP as first-line and 7 as either second- or third-line treatment. All patients received BDP together with a calcineurin inhibitor, except for 1 patient who was also receiving mycophenolate mofetil (MMF). BDP was administered for a minimum of 16 weeks and was tapered during 4 additional weeks. Of those patients receiving BDP as the first line of treatment, 22 (84.6%) achieved complete remission (CR) of GI cGVHD, 2 (7.7%) achieved a partial response (PR) and 2 (7.7%) did not respond or progressed. Median time to response was 28 days. Nevertheless, only 7 (27%) patients had maintained the response at last follow-up, whereas 19 (73%) finally relapsed or progressed. Median time to relapse was 147 days after the end of BDP. In the case of the patients who received BDP as a second- or third-line treatment, 3 (42.9%) achieved CR and 2 (28.6%) PR. For the whole series of patients, 13 patients (39.4%) were not receiving immunosuppressive treatment at final follow-up. Only 4 patients developed cytomegalovirus (CMV) reactivation, which was successfully treated with antiviral drugs. No fungal infection was observed during the treatment period. In conclusion, the current study shows that BDP, in the absence of systemic steroids, is a highly effective initial therapeutic approach for GI cGVHD, which helps to avoid complications related to systemic steroids.

The Use of Oral Beclomethasone Dipropionate in the Treatment of Gastrointestinal Graft-versus-host Disease: The Experience of the Fukuoka Blood and Marrow Transplantation (BMT) Group

“…Therefore, the development of new treatment strategies is required to avoid treatment-related morbidity in patients with mild GI-GVHD. The efficacy of oral BDP treatment has become increasingly evident and can be used to reduce systemic corticosteroid exposure in GI-GVHD patients (7,(15)(16)(17)(18)(19). In the present study, we assessed the efficacy of a treatment strategy for mild GI-GVHD using a combination of oral BDP and shortterm low-dose PSL based on the donor source.…”

“…As an anti-inflammatory agent, BDP has been shown to be 500-5,000 times more potent than dexamethasone and hydrocortisone (11,12). Based on encouraging observations in patients with inflammatory bowel disease (13,14), BDP has been increasingly used to treat GI-GVHD after allo-SCT, with high efficacy (7,(15)(16)(17)(18)(19). Prophylactic effects of oral BDP against early non-infectious pulmonary complications after allo-SCT have also been observed, and the administration of oral BDP can be used to reduce exposure to systemic corticosteroid therapy (6,20).…”

Rational use of chronic graft-versus-host treatment alternatives: A systematic review

“…In a retrospective study of Villanueva (2009), oral beclamethasone and cyclosporine were used in 33 patients with severe gastrointestinal involvement. At the end of 16 weeks, they achieved a CR of 84.6 % and a -indicates high risk of bias.…”

Enfermedad injerto contra huésped crónica: factores pronósticos y nuevas opciones terapéuticas

“…El alo-TPH afecta la función timica y la reconstitución de células T de manera que la pobre reconstitución de linfocitos T reg puede dar lugar a la incapacidad de suprimir las células auto y aloreactivas contribuyendo a la aparición de la EICH. En un estudio reciente en pacientes sometidos a alo-TPH (de los cuales un grupo de pacientes tenia EICHc activa y otro sin EICHc) y donantes sanos se demostró que los linfocitos T reg así como la expresión de FOXP3 se encuentran disminuidos en los pacientes con EICHc activa 50 . La causa de la disminución de esta población de linfocitos T en el contexto de la EICHc no está clara.…”

“…We described the efficacy and safety of BDP in a series of 33 patients with GI cGVHD 50 . We observed 84,6% CRs and 7,7% PRs among patients receving BDP as first-line treatment, whereas these figures were 42,9% and 28,6%, respectively, among patients receiving it as more than first-line treatment.…”