2022年 · 第102卷第28期

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome. Unlike pediatric patients, most adult patients have no clear familial HLH (FHL) gene defects, and about 50% are accompanied by underlying neoplastic diseases, among which hematological tumors (HM) are the most common. The incidence of HLH in adult patients with HM is about 1.0%, and it can reach 2.8% in patients with lymphoma. The development of diagnostic criteria for HLH-2004 is mainly for pediatric FHL, and its applicability to HM-HLH is unclear. HM involves bone marrow, spleen, or tumor cells secreting soluble interleukin-2 receptor (sCD25), which may lead to diagnostic expansion. The HLH scoring system HScore was derived from a retrospective study. Although it was developed for adult HLH, sCD25 was not included, and the low proportion of HM in non-HLH patients limited its application in the diagnosis of HM-HLH. In order to improve and simplify the diagnosis of HLH in patients with HM, the study retrospectively analyzed data from a total of 225 adult patients with HM from 6 centers in the United States, Japan, and Israel, of whom 65% were suspected of HLH and 35% were routinely tested. Classification and regression trees and subject operating characteristic curves were applied to determine the most useful diagnostic and prognostic parameters and to optimize laboratory cutoffs, according to whether HLH-2004 criteria were met or not, divided into HLH and non-HLH groups. The results showed that the combined elevation of sCD25 (>3 900 U/ml) and ferritin (>1 000 μ g/L) best identified the HLH-2004 defining features (84% sensitivity, 81% specificity), referring to this combination as the optimized HLH inflammation (OHI) index. The OHI index is highly predictive of mortality risk in different types of HMs (HR=4.3，95%CI：3.0～6.2）； When the OHI index was applied to assess the risk of death in patients with HM, a proportion of patients at high risk of death were not diagnosed with HLH according to the HLH-2004/HScore criteria.

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a fatal disease characterized by pathological immune activation and excessive inflammation. Etoposide-based regimens of HLH-94 and HLH-04 remain widely accepted as standard therapy, and while this greatly improves survival in patients with HLH, a considerable number of patients remain ineffective or unable to tolerate intense chemotherapy. Because HLH is associated with the overproduction of a large number of cytokines, blocking the pathogenic cytokines can significantly improve the efficacy and improve the prognosis. Rucotinib, an inhibitor of JAK1 and JAK2, can inhibit the signal transduction of interferon-γ and other key pro-inflammatory cytokines by inhibiting the JAK1/2-STAT1 pathway, and is a promising option for the treatment of HLH. The efficacy of ruxolitinib in the treatment of refractory/relapsed HLH has also been reported in a series of HLH cases, and related studies have shown that ruxolitinib is safe and effective in the treatment of HLH. However, there is still a lack of reliable data on the efficacy of ruxolitinib alone as a first-line drug. To explore the efficacy of ruxolitinib alone as a first-line agent and whether stratified therapy based on ruxolitinib response would lead to more beneficial outcomes for patients.

Hemophagocytic lymphohistiocytosis (HLH) can be divided into primary HLH (pHLH) and secondary HLH (sHLH) according to different etiologies. pHLH is usually caused by genetic defects that cause impaired cytotoxic lymphocyte function or dysfunction of inflammasomes. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important means to cure pHLH, but the myeloablative pretreatment regimens used before previous transplantation: Maryland (Bu) and cyclophosphamide (Cy), are often accompanied by severe drug toxicity and high mortality. Previous studies have found an 18% incidence of hepatic veno-occlusive disease (VOD) and an early mortality rate of 35% in HLH patients receiving a myeloablative preconditioning regimen. There are studies using reduced-dose pretreatment regimens: alemtuzumab, fludarabine (Flu) and melfaran (Mel). The toxicity and early mortality associated with chemotherapy regimens are very low, but the resulting mixed chimerism rate and graft implantation failure rate are high. In order to balance the differences between the two different pretreatment schemes, the pretreatment scheme of HLH has been continuously adjusted, but no study has been made to directly compare the results of different pretreatment schemes. The study analyzed the effects of groups of different intensity preconditioning regimens on post-transplant outcomes to determine one or more optimal regimens for the treatment of HLH.