Comparison of immunosuppressant regimens in salvage cord blood transplantation for graft failure after allogeneic hematopoietic stem cell transplantation
Bone marrow transplantation. 2020
Graft failure (GF) is a life-threatening complication after allogeneic stem cell transplantation. Although salvage cord blood transplantation (CBT) is a curative therapy for GF, the optimal immunosuppression after salvage CBT remains unknown. Using nationwide registration data, we compared the transplant outcomes of patients who developed GF and underwent salvage CBT using immunosuppressants, including calcineurin (CNI) alone (n?=?177); CNI plus methotrexate (CNI+MTX, n?=?150); and CNI plus mycophenolate mofetil (CNI+MMF, n?=?161). The CNI+MMF group, in comparison with the CNI+MTX and CNI alone groups, demonstrated better neutrophil recovery at 30 days (62.7 vs. 42.7 vs. 53.1%, P?0.001); better overall survival (OS) at 12 months (48.4 vs. 33.5 vs. 28.3%, P?0.001); and lower non-relapse mortality (NRM) at 12 months (35.2 vs. 53.9 vs. 56.5%, P?0.001). On multivariate analysis, CNI+MMF had the best neutrophil recovery (hazard ratio (HR), 1.71; P?0.001) and OS (HR, 0.64; P?=?0.002) and the lowest NRM (HR, 0.53; P?0.001). Hemorrhage was relatively less frequent in the CNI+MMF group. CNI+MMF can be a promising immunosuppressant regimen after salvage CBT for GF, with better engraftment and survival outcomes, compared with CNI alone and CNI+MTX.
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.
Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GvHD: an analysis of the JSHCT
Bone Marrow Transplantation. 2017;52(2):252-257
A nationwide retrospective study for the clinical outcomes of 99 patients who had received thymoglobulin at a median total dose of 2.5mg/kg (range, 0.5-18.5mg/kg) as a second-line treatment for steroid-resistant acute GvHD was conducted. Of the 92 evaluable patients, improvement (complete or partial response) was observed in 55 patients (60%). Multivariate analysis demonstrated that male sex and grade III and IV acute GvHD were associated with a lower improvement rate, whereas thymoglobulin dose (<2.0, 2.0-3.9 and 4.0mg/kg) was NS. Factors associated with significantly higher nonrelapse mortality included higher patient age (50 years), grade IV acute GvHD, no improvement of GvHD and higher dose of thymoglobulin (hazard ratio, 2.55; 95% confidence interval, 1.34-4.85; P=0.004 for 2.0-3.9mg/kg group and 1.79; 0.91-3.55; P=0.093 for 4.0mg/kg group). Higher dose of thymoglobulin was associated with a higher incidence of bacterial infections, CMV antigenemia and any additional infection. Taken together, low-dose thymoglobulin at a median total dose of 2.5mg/kg provides a comparable response rate to standard-dose thymoglobulin reported previously, and <2.0mg/kg thymoglobulin is recommended in terms of the balance between efficacy and adverse effects.