Published online Mar 26, 2020. doi: 10.12998/wjcc.v8.i6.1065
Peer-review started: November 22, 2019
First decision: December 12, 2019
Revised: February 19, 2020
Accepted: February 28, 2020
Article in press: February 28, 2020
Published online: March 26, 2020
Processing time: 124 Days and 13.7 Hours
Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Steroids are an important component of the strategy against GVHD, but some patients have steroid-refractory (SR) GVHD. Ruxolitinib is an inhibitor of JAK1/2-STAT signaling and exerts a unique anti-GVHD action.
There are limited data on the effects of ruxolitinib in patients with GVHD in China. Determining the clinical benefits of ruxolitinib in patients with GVHD could help improve their management.
This study evaluated the clinical effectiveness and adverse effects of ruxolitinib by retrospectively analyzing 38 patients in China with refractory GVHD after allo-HSCT who were treated with ruxolitinib add-on to standard immunosuppressive agents.
This single-center, retrospective case series included consecutive patients with SR-GVHD who received ruxolitinib at the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology (China), between May 2017 and March 2018. All patients received 5-10 mg ruxolitinib per d orally as an add-on immunosuppressive therapy. Treatment responses were evaluated every 3 mo. The grading of acute (a) GVHD used the modified Glucksberg standards. The overall grading of chronic (c) GVHD and the severity scores for various organs were determined using the 2015 version of the National Institutes of Health standards.
The analysis included 10 patients with SR-aGVHD (grade III/IV, n = 9) and 28 patients with SR-cGVHD (moderate/severe, n = 24). The median number of previous GVHD therapies was 2 (range: 1-3) and 2 (1-4) for the SR-aGVHD and SR-cGVHD groups, respectively. During a median follow-up of 2.5 (1.5-4) and 5 (1.5-10) mo, the objective response rates were 100% (complete response, 80%) for aGVHD and 82% for cGVHD. Nevertheless, there was a risk of malignancy relapse, with rates of 10.0% and 10.7% for the SR-aGVHD and SR-cGVHD groups, respectively. The reactivation rates for cytomegalovirus, Epstein-Barr virus and varicella-zoster virus were 30.0%, 10.0% and 0% for the SR-aGVHD group and 0%, 14.3% and 7.1% for the SR-cGVHD group.
Ruxolitinib induces clinical benefits in patients with GVHD, with a good profile of complications and adverse effects. Therefore, it could be hypothesized that ruxolitinib improves the quality of life of patients with SR-GVHD compared with the standard immunosuppressive regimens. Of note, the dosage of ruxolitinib (5-10 mg/d) used here was lower than those in these other studies (10-20 mg/d). This might be because of concomitant azole anti-fungal, which could increase the half-life of ruxolitinib by competing for the same cytochromes.
Ruxolitinib has been suggested as a possible novel therapy for GVHD with less toxicity than standard immunosuppressive agents. Future studies and clinical trials should look into the optimization of the ruxolitinib regimens for the individualized management of GVHD.