Cytokine Guided Risk Stratification and Treatment in Pediatric Hemophagocytic Lymphohistiocytosis

Summary

Hemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune-dysregulation characterized by hypercytokinemia, with about 30%-40% of patients suffering death in children. Stratification strategy and individualized treatment is important to improve the survival. In our recent retrospective study, risk stratification based on IL-10 and IFN-γ levels well distinguished patients with different outcomes. In this multicenter prospective study, we will enroll the newly diagnosed pediatric HLH patients and divide them into low, intermediate and high-risk cytokine groups according to IFN-γ and IL-10 levels. The patients'clinical manifestation and laboratory findings will be further evaluated into severe and non-severe groups. For low/intermediate risk and non-severe patients, steroid or ruxolitinib will be used initially; while those with high risk or severe diseases, DXM+VP16±ruxolitinib will be administered. The treatment strategy could be adjusted after evaluation 48-72 hours later.

Conditions

• Hemophagocytic Lymphohistiocytoses
• Cytokine Storm

Interventions

DRUG

Dexamethasone

Single drug in non-severe group; combined with etoposide±ruxolitinib in severe group.

DRUG

Etoposide

Used in severe group combined with etoposide.

DRUG

Ruxolitinib

Single drug in non-severe group; combined with etoposide and dexamethasone in severe group.

Sponsors & Collaborators

• The Second Hospital of Anhui Medical University

  collaborator OTHER

• Union hospital of Fujian Medical University

  collaborator OTHER

• Children's Hospital of Fudan University

  collaborator OTHER

• Zunyi Medical College

  collaborator OTHER

• Hunan Provincial People's Hospital

  collaborator OTHER

• Tongji Hospital

  collaborator OTHER

• Children's Hospital of Nanjing Medical University

  collaborator OTHER

• The Affiliated Hospital of Qingdao University

  collaborator OTHER

• Qilu Hospital of Shandong University

  collaborator OTHER

• Shanghai Children's Medical Center

  collaborator OTHER

• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

  collaborator OTHER

• Shanghai Children's Hospital

  collaborator OTHER

• Shenzhen Children's Hospital

  collaborator OTHER_GOV

• West China Second University Hospital

  collaborator OTHER

• Children's Hospital of Soochow University

  collaborator OTHER

• Second Affiliated Hospital of Wenzhou Medical University

  collaborator OTHER

• Wuhan Children's Hospital

  collaborator OTHER

• Institute of Hematology & Blood Diseases Hospital, China

  collaborator OTHER

• The Third Xiangya Hospital of Central South University

  collaborator OTHER

• First Affiliated Hospital, Sun Yat-Sen University

  collaborator OTHER

• The Children's Hospital of Zhejiang University School of Medicine

  lead OTHER

Principal Investigators

• Xiaojun Xu, MD · The Children's Hospital of Zhejiang University School of Medicine

• Yongmin Tang, MD · The Children's Hospital of Zhejiang University School of Medicine

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Day

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-09-01

Primary Completion

2024-12-31

Completion

2025-12-31

Countries

• China

Study Locations