Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of severe acute and chronic gastrointestinal (GI) graft-versus-host disease (GVHD) with prolonged high-dose systemic corticosteroids has limited success and considerable toxicity. Beclomethasone dipropionate (BDP) is a potent topically active steroid. We treated 15 patients with acute (n = 2) or chronic (n = 13) GI GVHD refractory to systemic corticosteroids with 28-day courses of oral BDP (2 mg 4 times daily). Response was measured by the change in GI score (sum of 6 GI symptoms) as well as the ability to taper or discontinue systemic corticosteroids. Nine (60%) of 15 evaluable patients responded to BDP, including 3 complete responses (a GI score of 0 or 1 and discontinuation of systemic corticosteroids). Attempts to taper calcineurin inhibitor during BDP therapy were unsuccessful. The 2 patients with acute GVHD had no response to BDP. Responders received a median of 3 cycles (range, 1-20), compared with 1 cycle (range, 1-5) in nonresponders. Suppression of the hypothalamic-adrenal axis was seen in 2 of the 5 patients tested, but neither demonstrated clinically significant symptoms. We conclude that BDP is safe and effective for long-term treatment of chronic GI GVHD. Multiple courses may be necessary to achieve or maintain response in some patients, and prolonged BDP therapy is a feasible alternative to prolonged systemic corticosteroids.
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PMID:Long-term use of oral beclomethasone dipropionate for the treatment of gastrointestinal graft-versus-host disease. 1604 8

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.
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PMID:Oral beclomethasone dipropionate for the treatment of gastrointestinal acute graft-versus-host disease (GVHD). 1692 May 59

Beclomethasone dipropionate (BDP) is a topically active anti-inflammatory corticosteroid. Oral BDP is metabolized in the intestine to a potent metabolite, 17-beclomethasone monopropionate (17-BMP). An oral formulation (orBec; DOR BioPharma), consisting of a gastric release and an enteric-coated pill, was studied in patients with acute gastrointestinal graft-versus-host disease, an inflammatory disorder that is common after allogeneic hematopoietic cell transplantation. Randomized trials demonstrated that orBec is safe and effective in treating acute gastrointestinal graft-versus-host disease (GVHD) when used with a short induction course of prednisone, reducing the risk of GVHD treatment failure by > 60% and reducing mortality 1 year after randomization by 45%, with fewer deaths due to infection and recurrent malignancy. The type of conditioning and the type of donor had no effect on the frequency of GVHD treatment failure during the 80-day study period; the greatest benefit in terms of survival was among patients who had received reduced-intensity conditioning therapy and among those who received a graft from other than a human leukocyte antigen-matched sibling. orBec controls the intestinal inflammatory process of GVHD and avoids prolonged exposure to prednisone, which is the present standard of care. Oral BDP is the only therapy to be studied in the last 30 years to effectively treat acute GVHD and reduce mortality.
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PMID:Oral beclomethasone dipropionate: a topically active corticosteroid for the treatment of gastrointestinal graft-versus-host disease following allogeneic hematopoietic cell transplantation. 1792 33

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.
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PMID:Oral beclomethasone dipropionate for the treatment of gastrointestinal chronic graft-versus-host disease. 1974 42

Beclomethasone dipropionate is a corticosteroid with topical activity for inflammatory disorders at mucosal surfaces. Oral beclomethasone dipropionate (orBec) has demonstrated activity in gastrointestinal acute graft-versus-host disease (aGVHD) associated with hematopoietic cell transplantation. Since the GI tract is the dominant aGVHD target in many patients, oral beclomethasone dipropionate reduces the requirement for systemic immunosuppressive drugs in treating aGVHD. In this patient population, reduced exposure to systemic corticosteroids is associated with fewer infections and, possibly, preserved graft-versus-tumor effects, yielding a statistically significant improvement in survival in a randomized, multicenter clinical trial.
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PMID:Oral beclomethasone dipropionate in gastrointestinal graft-versus-host disease. 2047 20