Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Mar 26, 2020; 8(6): 1065-1073
Published online Mar 26, 2020. doi: 10.12998/wjcc.v8.i6.1065
Ruxolitinib add-on in corticosteroid-refractory graft-vs-host disease after allogeneic stem cell transplantation: Results from a retrospective study on 38 Chinese patients
Si-Hua Dang, Qin Liu, Rong Xie, Na Shen, Shu Zhou, Wei Shi, Wen Liu, Ping Zou, Yong You, Zhao-Dong Zhong
Si-Hua Dang, Rong Xie, Na Shen, Shu Zhou, Wei Shi, Wen Liu, Ping Zou, Yong You, Zhao-Dong Zhong, Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Si-Hua Dang, Department of Oncology, Luohe Central Hospital, Luohe 462300, Henan Province, China
Qin Liu, Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: Dang SH and Liu Q contributed equally to this article, conceived of and coordinated the study, designed, performed, and analyzed the experiments, and wrote the paper; Xie R, Shen N, Zhou S, Shi W, Liu W, and Zou P performed the data collection and data analysis, and revised the paper; You Y and Zhong ZD designed the study, carried out the data collection and data analysis, and revised the paper; All authors reviewed the results and approved the final version of the manuscript.
Institutional review board statement: This study was approved by the institutional review board of the Union Hospital of Tongji Medical College.
Informed consent statement: Waived because of the retrospective study design.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zhao-Dong Zhong, MD, Doctor, Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hankou District, Wuhan 430030, Hubei Province, China. whxhzzd008@126.com
Received: November 22, 2019
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
ARTICLE HIGHLIGHTS
Research background

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.

Research motivation

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.

Research objectives

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.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

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.