Treatment and theoretical "double" breakthrough, Beijing Children's Hospital has made important progress in the study of children's blood cell syndrome research

Author:Physician reported tumor chann Time:2022.09.01

Hemophagocytic Lymphohistiocytosis (HLH) is a pathological excessive inflammatory syndrome that threatens life. HLH-1994 and HLH-2004 solutions based on hormone and pupinoside have significantly improved the survival rate of HLH patients. It is still a widely used HLH standard treatment scheme. However, about 30%-50%of patients are not sensitive to the treatment of the above plan, or severe bone marrow suppression due to strong chemotherapy, combined infection, and high treatment related mortality. In addition, some patients with severe organs damage are not suitable for high -intensity chemotherapy, making it difficult to balance the emergency treatment needs of the disease and reduce the treatment of related toxic and side effects.

Rukatinib

Can be used as a first -line medication for HLH treatment

Recently, Professor Wang Tianyou, Professor Zhang Rui and Professor Zhang Rui in Beijing Children's Hospital, Beijing Children's Hospital, cooperated with Professor Li Zhigang in the Herbal Disease Research Office of the Beijing Children's Research Institute to diagnose the diagnosis of children's blood cell syndrome (HLH) diagnosis Obtain important research progress in the field of treatment, related research results were published in the international well -known international journal "Blood" (influencing factor 25.476) and "Journal of Hematology onCology" (influence factor 23.168).

Recently, with the in -depth understanding of the HLH immunology mechanism, the targeted therapy for key cytokines that mediates HLH shows important application prospects in HLH treatment. Ruxolitinib (RUX) is a kind of oral JAK1 and JAK2 tyrosine kinase inhibitors. It can block a series of mediated HLH pathological cytokines, such as ifn -γ, IL-6, IL10, etc., many clinical basic research and small sample case reports have proved that RUX can effectively inhibit cytokine storms, suggesting that RUX has important clinical application prospects in HLH treatment. However, these studies are mainly focused on the treatment of adult HLH patients with RUX as the treatment of adult HLH. They still lack the reliable clinical data with RUX single drugs as the first -line solution, especially in the children's HLH group.

On June 16, 2022, Professor Wang Tianyou, Professor Zhang Rui and Professor Zhang Rui and Professor Li Zhigang in Beijing Children's Research Institute of Herbal Institute of Health Diseases in Beijing Children's Hospital. "A Study of Ruxolitinibresponse-Based Stratify Treatment for Pediatric Hemophoglyticlymphohistiocytosis". This study took the lead in conducting clinical studies with HLH, the first diagnosis of children's HLH for first -line drug treatment, and 8 -layered treatment based on early treatment reactions of the first -line treatment of rectinib, in order to reduce non -necessary chemotherapy, reduce chemotherapy -related poisonous poisoning Side effects and mortality.

There were 52 cases of HLH children with a total of 73.1%, and a total of 86.4%of the total survival in one year was 86.4%. , Significantly reduced the non -necessary chemotherapy of HLH children. The study also found that the first -line treatment response of Rukatinib has no clear correlation with the HLH baseline index grading, which is significantly related to the type of original disease. Among them, the EB virus infection correlation HLH (EBV-HLH) is sensitive to reaction to the treatment of rectinib, especially the initial explosive EBV infection related HLH is very good. There may be significant differences.

This study has proved that children's HLH layered treatment based on the early treatment reactions based on the early treatment reactions of Rukatinib has high feasibility. It has high feasibility. The limitation of plan treatment, promote individualized precision diagnosis and treatment of HLH children, and reduce treatment related mortality. The special review of the editor -in -chief of "Blood" magazine fully affirmed the important clinical significance of the study. Professor Zhang Rui, Professor Wang Tianyou, and Professor Li Zhigang communicated as the author of this article. Acting researcher Zhang Qing and the second subject of the blood of the blood disease and the attending physician of the blood of the blood of the blood was the first author of this article.

Reveal the NBAS mutation gene

In the HLH pathogenesis

On July 28, 2022, another research results collaborated by Beijing Children's Hospital and the Beijing Institute of Genome (National Biological Information) of the Chinese Academy of Sciences (National Biological Information Center) were based on the "NBAS, A Gene Involved in Cytotoxic Degranulating, is recurrentlymutric hemphohistic Title, published in "Journal of Hematology onCology". The cause and pathogenesis of HLH are very complicated. Among them, congenital genetic defects are one of the main reasons for children's HLH. Under the extensive clinical application of genetic testing, the clear diagnosis and targeted treatment of HLH patients have achieved significant results. However, the detection rate of primary HLH related genes currently used for clinical diagnosis is still low (about 10%), and only a small number of patients can be explained. In clinical work, a considerable part of the patients (about 30%) on the onset of infants and young children, unknown causes, difficult to cure the disease or multiple recurrences. The genetic foundation is far from clear. This brings great limitations and difficulties to the choice of early precision diagnosis and treatment plan for children, and eventually leads to poor prognosis.

In response to this problem, the team of Professor Wang Tianyou, Professor Zhang Rui, and Professor Li Zhigang, and the Beijing Academy of Sciences Beijing Institute (National Biological Information Center) Wang Qianfei and Liu Xin team carried out research on children's HLH genetic mutations. The study uses the rich clinical resources of Beijing Children's Hospital, combined with the sequencing information of the outer surgery group and the patient clinical table type, and through objective analysis and independent verification, the NBAS gene mutations with high reproducibility in the children's HLH group have been identified. And combined with molecular biological function experiments reveal the internal molecular mechanism of the gene in HLH.

This study deepened the understanding of HLH genetic background and pathogenesis. At the same time, in view of the high reproducibility of NBAS gene mutations in the HLH crowd, this research results are also expected to be used for clinical regular screening and guide early precision diagnosis and treatment of HLH. Professor Zhang Rui, Researcher Wang Qianfei, and Researcher Liu Xin communicated with the author of this article. co-author.