Use of unapproved or off-label drugs in Japan for the treatment of graft-versus-host disease and post-transplant viral infection
International journal of hematology. 2020
Many drugs are used for unapproved indications in Japan for post hematopoietic stem cell transplant (HCT) complications. To investigate unapproved or off-label drug usage for graft-versus-host disease (GVHD) and virus infections after allogeneic HCT, we analyzed the data of Japanese HCT registry. Between 2006 and 2017, 39,941 adults and children received HCT for a variety of disease and their transplant data were captured in the registry. Among them, 14,687 and 8914 patients receiving treatment for acute and/or chronic GVHD, 24,828 patients with cytomegalovirus (CMV) infection or receiving therapies for CMV, and 4943 who received treatment for other viral infections were included in the analyses of off-label or unapproved drugs. For GVHD, mycophenolate mofetil was the most frequently used off-label drug, followed by beclomethasone, infliximab, and etanercept. For viral infections other than CMV, foscarnet was the most frequently used off-label drug. Cidofovir, which is not approved for use in Japan, was mainly used for adenovirus infection. This study demonstrated that numerous off-label and unapproved drugs have been used as key drugs for GVHD and post-transplant viral infection, and the real world date in the transplant registry may serve as an important asset to regulatory purposes.
Impact of cumulative steroid dose on infectious diseases after allogenic hematopoietic stem cell transplantation
Transplant infectious disease : an official journal of the Transplantation Society. 2019;:e13049
BACKGROUND Systemic steroid is used to treat various transplant-related complications after allogenic hematopoietic stem cell transplantation (allo-HSCT). However, measures to evaluate its impact on infections are still limited. Hence, we examined the cumulative steroid dose used within 30 days after transplant as a predictor of future risk of infections. METHODS This study included 226 patients who underwent their first allo-HSCT at Kyoto University Hospital between 2005 and 2015. RESULTS Sixty-one patients received transplantation from related donors, 106 received unrelated BMT and 59 received unrelated single-unit CBT. Patients were categorized into 3 groups according to the cumulative steroid dose in terms of prednisolone: no-steroid group (n=174), low-dose group (<=7mg/kg) (n=22) and high-dose group (>7mg/kg) (n=30). In a multivariate analysis, high-dose steroid administration was associated with CMV antigenemia (HR 1.91, P=0.037) and bacteremia (HR 2.59, P=0.053). No impact was found on the occurrence of invasive fungal infection. CONCLUSION High-dose cumulative steroid could predict high risks of bacteremia and CMV antigenemia. Additional anti-bacterial agents for fever and regular measurement of CMV antigen are recommended for whom with systemic steroid administration even after neutrophil engraftment. This article is protected by copyright. All rights reserved.
Association of Cumulative Steroid Dose with Risk of Infection after Treatment for Severe Acute Graft-versus-Host Disease
Biology of Blood & Marrow Transplantation. 2016;22(6):1102-7
This study aimed to characterize the incidence and risk factors of invasive fungal disease, cytomegalovirus infection, other viral diseases, and gram-negative rod infection after glucocorticoid treatment for severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation and to elucidate the associations of cumulative steroid dose with the risks of individual infections. The study cohort included 91 consecutive patients who developed maximum grades III and IV acute GVHD at our center. The mean cumulative prednisolone-equivalent dose was 41 mg/kg during the first 4 weeks. The cumulative incidence rates of fungal disease, cytomegalovirus disease, other viral diseases, and gram-negative rod infection at 6 months after glucocorticoid treatment were remarkably high, at 14%, 21%, 28%, and 20%, respectively. GVHD within 26 days after transplantation and low lymphocyte count at GVHD treatment were associated with increased risks of several infections. Cumulative prednisolone-equivalent steroid doses > 55 mg/kg during the first 4 weeks were associated with an increased risk of fungal disease (hazard ratio, 3.65; P = .03) and cumulative doses > 23 mg/kg were associated with an increased risk of non-cytomegalovirus viral diseases (hazard ratio, 4.14; P = .02). Strategies to reduce the risk of infectious complications are needed, particularly for patients who have risk factors and those who receive high cumulative steroid doses. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.