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Ferrata Storti Foundation
Haematologica 2021 Volume 106(7):1892-1901
Hemophagocytosis
A pilot study of ruxolitinib as a front-line therapy for 12 children with secondary hemophagocytic lymphohistiocytosis
Qing Zhang,1* Ang Wei,2* Hong-Hao Ma,2 Li Zhang,2 Hong-Yun Lian,2
Dong Wang,2 Yun-Ze Zhao,2 Lei Cui,1 Wei-Jing Li,1 Ying Yang,2 Tian-You Wang,2 Zhi-Gang Li,1# and Rui Zhang2#
1Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health and 2Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Key Laboratory of Major Diseases in Children, Ministry of Education, Department of Hematology Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
#QZ and AW contributed equally as co-first authors. #ZL and RZ contributed equally as co-senior authors.
ABSTRACT
Hemophagocytic lymphohistiocytosis (HLH) is an immune-regula- tory disorder characterized by excessive production of inflamma- tory cytokines. The treatment recommendations of the HLH- 1994 and HLH-2004 protocols have long been used in HLH therapy, but some patients still do not respond well to or have unacceptable side effects from conventional therapies. It is believed that cytokine-targeted strategies that directly target disease-driving pathways will be promising options for HLH. This prospective study aimed to investigate the effica- cy and safety of ruxolitinib, a Janus kinase 1/2 inhibitor, as a front-line therapy in children with secondary HLH. Twelve newly diagnosed patients without previous treatment were enrolled in this study with a median follow-up of 8.2 (range, 7.1-12.0) months, including eight cases of Epstein-Barr virus associated HLH (EBV-HLH), two cases of autoin- flammatory disorder (AID)- associated HLH, and two cases of unknown etiology. Patients received oral ruxolitinib dosed on 2.5 mg, 5 mg or 10 mg twice daily depending on the body weight for 28 consecutive days. The overall response rate at the end of treatment (day 28) was 83.3% (ten of 12), with 66.7% (eight of 12) in complete response (CR), 8.3% (one of 12) in partial response (PR), and 8.3% (one of 12) in HLH improvement. Among the patients achieving CR, 87.5% (seven of eight) maintained CR condition more than 6 months, and one patient with EBV-HLH relapsed following CR. For the EBV-HLH subgroup, all eight patients responded to ruxolitinib, with a CR rate of 75% and a PR rate of 25%. Two patients with AID-associated HLH had quite different responses, with one show- ing reversal of the HLH abnormalities soon and the other showing no improvement, as did the two cases of unknown etiology. Patients who had no response or discontinued ruxolitinib all responded well to the sub- sequent HLH-1994 regimen. The expected 6-month event-free survival rate was 58.3±10.2%. No serious adverse effects were reported. Our study provides further support for the possibility of ruxolitinib targeted therapy for secondary HLH in children. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as clinicaltrials gov. Identifier: ChiCTR2000029977.
Introduction
Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder characterized by uncontrolled T-lymphocyte and macrophage activation and excessive production of inflammatory cytokines. Patients present with multiple clinical features, including
Correspondence:
RUI ZHANG
ruizh1973@126.com
ZHI-GANG LI
ericlzg70@hotmail.com
Received: April 2, 2020. Accepted: July 21, 2020. Pre-published: July 30, 2020.
https://doi.org/10.3324/haematol.2020.253781
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