(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Hematologic-Neoplasms

Topics: Administration, Oral; Anti-Inflammatory Agents; Beclomethasone; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Gastrointestinal Diseases; Graft Rejection; Graft vs Host Disease; Hematologic Neoplasms; Humans; Lung Diseases; Stem Cell Transplantation; Tablets, Enteric-Coated

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.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Beclomethasone; Biopsy; Chronic Disease; Female; Follow-Up Studies; Gastrointestinal Diseases; Graft vs Host Disease; Hematologic Neoplasms; Humans; Male; Middle Aged; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Transplantation, Homologous

Acute graft-versus-host disease (aGVHD) remains one of the most severe complications after allogeneic transplantation; in particular, the presence of gut involvement has been related to increased mortality and poorer response. The use of systemic steroids remains the standard for first-line treatment despite its severe secondary effects. Beclomethasone dipropionate (BDP) is a topically active corticosteroid with low absorption, thereby avoiding many of the deleterious side effects associated with systemic steroids. In the present study we analyzed the efficacy of BDP in a series of 26 patients who were diagnosed with grade 1 and 2 gastrointestinal aGVHD. Twenty patients (77%) responded to BDP treatment, 17 (65.5%) reached complete remission (CR), and 3 (11.5%) showed partial response. Among those patients who reached CR, 5 relapsed, although 1 of them reached second CR after a second course of BDP; therefore, 13 (50%) of the 26 patients did not require systemic steroids to treat gastrointestinal aGVHD. CR rates in those showing gastrointestinal symptoms were 68% for patients with persistent nausea, 50% for those with vomiting, and 54% for those with diarrhea (P=.2). No patient included in the study developed any symptom related to adrenal axis suppression. Thirteen patients (50%) developed >or=1 infectious episode during the first 100 days after transplantation. Transplant-related mortality was 0% at 100 days, and overall transplant-related mortality was 30%, with only 2 patients dying due to infectious complications. Therefore, our study shows that monotherapy with oral BDP is an effective initial therapeutic approach for mild to moderate intestinal GVHD, which avoids complications related to systemic steroids.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Disease-Free Survival; Female; Gastrointestinal Diseases; Graft vs Host Disease; Hematologic Neoplasms; Humans; Male; Middle Aged; Time Factors

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Allografts; Anti-Inflammatory Agents; Beclomethasone; Cord Blood Stem Cell Transplantation; Female; Gastrointestinal Diseases; Graft vs Host Disease; Hematologic Neoplasms; Humans; Male; Middle Aged