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
Abstract
BACKGROUND

Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation. Some patients have steroid-refractory (SR) GVHD.

AIM

To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.

METHODS

We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered 5-10 mg/d depending on disease severity, patient status, and the use of anti-fungal drugs. Overall response rate, time to best response, malignancy relapse rate, infection rate, and treatment-related adverse events were assessed.

RESULTS

The analysis included 10 patients with SR-aGVHD (grade III/IV, n = 9) and 28 patients with SR-cGVHD (moderate/severe, n = 24). For the SR-aGVHD and SR-cGVHD groups, respectively: Median number of previous GVHD therapies was 2 (range: 1-3) and 2 (1-4); median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo; median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo; and overall response rate was 100% (complete response: 80%) and 82.1% (complete response: 10.7%) with a response observed in all GVHD-affected organs. The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0% and 10.7%, respectively. Reactivation rates for cytomegalovirus, Epstein-Barr virus, and varicella-zoster virus, respectively, were 30.0%, 10.0%, and 0% for the SR-aGVHD group and 0%, 14.3%, and 7.1% for the SR-cGVHD group.

CONCLUSION

Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.

Keywords: Graft-vs-host disease; Graft-vs-leukemia effect; Allogeneic hematopoietic stem cell transplantation; Ruxolitinib; Treatment; Antifungal drugs

Core tip: This study aimed to investigate the effect and safety of ruxolitinib add-on in the treatment of patients with steroid-refractory (SR) acute (a) and chronic (c) graft-vs-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. An important finding of this retrospective case series was that the use of ruxolitinib as a salvage therapy for SR-GVHD resulted in an overall response rate of 100% in patients with SR-aGVHD (complete response: 80%) and 82.1% in patients with SR-cGVHD (complete response: 10.7%). In addition, this was achieved with a lower dose (5-10 mg/d) of ruxolitinib than previous reports, indicating that the dose of ruxolitinib could be lowered when used in combination with antifungal drugs (CYP2C9/CYP3A4 inhibitors).