Volume 102 ·  Issue 28 ·  2022

Hemophagocytic lymphohistiocytosis is a rapidly progressive and highly fatal disease with no specific clinical manifestations and multiple potential etiologies. Timely initiation of appropriate treatment is the key to improvement of the prognosis. Timely, accurate, and complete diagnosis of hemophagocytic lymphohistiocytosis requires the three-step principle, which is suspected diagnosis, confirmed diagnosis, and etiological diagnosis. With the development of new diagnostic technologies and methods, the establishment of a standardized diagnostic system and the construction of clinical pathways for hemophagocytic lymphohistiocytosis, the diagnostic efficiency of the fatal disease has been continuously improved, and hemophagocytic lymphohistiocytosis has entered an era of standardized, path-based and individualized accurate diagnosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening entity which presents as multi-organ dysfunction caused by overactivated T cell and macrophage and overwhelming hyperinflammation. Cytokine storm is the key pathophysiology of HLH. Due to the diversity of the underlying diseases, the difference of disease severity and the non-specific clinical manifestation, the early diagnosis and standardized treatment is a great challenge for clinicians. According to previous clinical studies, serum cytokine measurement is helpful for rapid diagnosis of HLH and the differentiation of HLH from other diseases caused by hypercytokinemia, and it perfoms well to clarify subtypes of HLH, to stratify patients with different risks and to predict the prognosis and outcome. Thus, serum cytokine measurement could be a useful tool for the precise diagnosis and treatment of HLH.

Monkeypox is a rare infectious disease caused by the monkeypox virus, which used to occur endemically in central and western Africa. As of 25th May, a total of 219 recently confirmed cases of monkeypox have been reported from 19 non-endemic countries. This outbreak unusually takes place in non-endemic areas for monkeypox virus and has exhibited features of high risk of human-to-human transmission. Onset of multiple human monkeypox cases may be related to the decreased level of herd cross-immunity after the cessation of smallpox vaccination. Moreover, behavioral patterns in specific populations may account for the human-to-human transmission in this outbreak. Currently, possibility of global epidemic of monkeypox is extremely low, but China should be cautious about risks of importation of monkeypox cases. The key to prevention and control is to establish a surveillance system to identify suspicious cases and close contacts as soon as possible.

In recent years, there have been newly marketed anti-human epidermal growth factor receptor 2 (HER2) targeted drugs in clinical application, which has put forward new requirements for the standardized use and management of targeted drugs for medical staff. The infusion specification of accessible targeted drugs, the prevention and management of adverse reactions, etc. are important prerequisites for ensuring the efficacy and safety of drugs. Based on this, the Breast Cancer Case Manager Branch of China Medical Education Association and the Consensus Formulation Group of Targeted Drug Infusion Specifications discussed the currently available domestic drugs for injection trastuzumab 440 mg/bottle, 150 mg/bottle, 60 mg/bottle, pertuzumab 420 mg/bottle, emmetuzumab 100 mg/bottle, 160 mg/bottle as examples, and the common problems existing in the promotion and application of the published "Expert Consensus on Intravenous Infusion Specifications of Targeted Drugs for Breast Cancer". By improving the Delphi method, expert suggestions were collected, and consensus recommendations were formed, which updated the "Consensus" and provided a reference for medical staff in the clinical practice of targeted therapy management.

To evaluate the efficacy of rapid immunological indicator-degranulation function (CD107a) and perforin expression in the diagnosis of primary hemophagocytic lymphohistiocytosis (pHLH).

The clinical data of 295 HLH patients who underwent genetic screening from April 2015 to June 2020 in Beijing Friendship Hospital, Capital Medical University, Beijing Jingdu Children′s Hospital and Beijing Children′s Hospital, Capital Medical University was collected and analyzed. The fitness of CD107a and Perforin expression with genetic screening was compared to evaluate the sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of the two indicators, and the receiver operating characteristic (ROC) curves were generated and used to determine the optimal threshold (cut-off values) of CD107a and Perforin expression assays that would identify pHLH patients with a maximum sensitivity and specificity (Youden index).

In all 295 patients included, there were 156 males and 139 females, aged from 2 months to 70 years, with a median age of 18 years. In terms of distinguishing the type of pHLH associated with degranulation gene defect from all other genetic screening results, in the CD107a testing, the ROC curve was generated and showed an area under the curve (AUC) of 0.920 (P<0.001), and the optimal cut-off value was determined to be 7.15% with a sensitivity of 83.3% and specificity of 89.2% when the corresponding Youden index was maximized. The PPV and NPV were 33.3% and 98.8%, respectively. CD107a>10% had an accuracy of 81.6% in judging patients without degranulation-related gene defect and negative genetic screening results. In addition, in terms of distinguishing the type of familial hemophagocytic lymphohistiocytosis type 2 (FHL2) from all other genetic screening results, the sensitivity, specificity, PPV and NPV of the Perforin expression testing were 88.2%, 64.2%, 20.3% and 98.1%, respectively, based on the normal laboratory test value (≥ 81%). The ROC curve was established to further optimize the cut-off value. The AUC was 0.933 (P<0.001). The cut-off value corresponding to the maximum Youden index was 62.34%, and the sensitivity remained at 88.2%. While the specificity, PPV and NPV rose to 91.5%, 51.7% and 98.7%, respectively.

CD107a and Perforin assays have good significance of early prediction for pHLH involved in impaired cytotoxic function. Selecting appropriate cut-off values can provide basis for accurate clinical diagnosis.

To investigate the efficacy and safety of ruxolitinib, liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase (RU-DEP+/-L) in the treatment of relapsed/refractory (R/R) pediatric hemophagocytic lymphohistiocytosis (HLH).

The clinical data of R/R pediatric HLH, who accepted the RU-DEP+/-L regimen at Beijing Children′s Hospital from January 2018 to December 2019 was retrospectively analyzed.

A total of 16 patients were included in this study, including 13 males and 3 females, aged[M(Q₁,Q₃)] 1 (1, 2) years at diagnosis. Thirteen patients were diagnosed with Epstein-Barr virus (EBV)-HLH, 2 with EBV-induced primary HLH, and 1 with unclear etiology, among which 3 patients were co-infected with CMV. After the first-line treatment, 11 patients had no response, and 5 patients relapsed after complete response. Nine patients received the RU-L-DEP regimen, and 7 patients received the RU-DEP regimen. The overall response rate and complete response of RU-DEP+/-L treatment were 10/16 and 3/16, respectively. The negative conversion rate of plasma EBV-DNA was 7/15. The median follow-up time was 35.1 (2.4, 40.7) months, and 9/16 patients were survival. The 3-year overall survival rate after RU-DEP+/-L treatment in response and accepted hematopoietic stem cell transplantation (HSCT) was higher than that without response and did not receive HSCT (P=0.048). Among the 16 patients, 9 had varying degrees of myelosuppression, and 13 had an infection.

RU-DEP+/-L can be used as a salvage treatment in R/R pediatric HLH, which can provide a bridge to HSCT and play an important role in the control of HLH. The main adverse reactions are myelosuppression and infection, which can be tolerated.

Subjective To investigate clinical characteristics, treatment, and prognosis of lymphoma-associated hemophagocytic syndrome (LAHS) patients.

The clinical data of patients diagnosed with LAHS from January 2010 to October 2021 in West China Hospital were retrospectively analyzed. Clinical characteristics, treatment, overall response rate (ORR), and overall survival (OS) were investigated. Univariate and multivariate analysis of potential factors were conducted.

Of all 94 patients included, 59 were male and 35 were female. The age at hemophagocytic lymphohistiocytosis (HLH) diagnosis was (40.5±17.3) years. Seventy-four cases were T/NK cell lymphoma; 15 were B cell lymphoma; 5 were Hodgkin lymphoma. The age at HLH diagnosis of T/NK cell LAHS patients was (37.9±16.2) years, while that of B cell LAHS patients was (55.9±14.0) years. T/NK cell LAHS patients were significantly younger than B cell LAHS patients (P<0.001). Baseline fibrinogen of T/NK cell LAHS patients was 1.34 (0.86, 2.44) g/L, while that of B cell LAHS patients was 2.20 (1.75, 4.25) g/L. T/NK cell LAHS patients showed significantly lower fibrinogen levels than B cell LAHS patients (P=0.008). Combined treatment of anti-HLH and anti-lymphoma treatment was conducted in 35 patients; anti-HLH treatment was conducted in 31 patients; anti-lymphoma treatment was conducted in 8 patients; glucocorticoid treatment was conducted in 7 patients. ORR was 49.4%, and the median OS was 61 days for overall patients. Patients who received anti-HLH treatment and turned to anti-lymphoma treatment early displayed the best ORR and OS, significantly higher than those of anti-HLH patients (69.0 vs 38.7%, P=0.019, and 192.0 vs 24.5 days, P=0.028, respectively), which were also insignificantly higher than those of anti-lymphoma patients. Extranodal NK/T-cell lymphoma or aggressive natural killer cell leukemia was the risk factor of LAHS prognosis (HR=0.113, 95%CI: 0.018-0.728, P=0.022).

Prognosis of LAHS patients is poor. Anti-lymphoma treatment should be initiated as soon as HLH is rapidly controlled.

To explore the clinical characteristics, prognostic risk factors and effective treatment of severe hemophagocytic syndrome (HPS) in children, so as to provide reference for the clinical diagnosis and treatment of the disease.

The clinical data of 83 children with severe HPS admitted in Affiliated Hospital of Zunyi Medical University from January 2014 to April 2021 were collected, and their clinical characteristics, prognosis and prognostic risk factors were analyzed. The children were divided into central nervous system (CNS) dysfunction group and non-CNS dysfunction group according to whether they were accompanied with CNS dysfunction, and were divided into blood purification group and non-blood purification group according to whether they received blood purification, then the survival differences were compared.

Among the 83 children, there were 43 males and 40 females, aged[M(Q₁,Q₃)] 36(15,27)months. A total of 51 children were induced by infection, among which 41 children (80.4%) were infected with EB virus. All the children were accompanied by multiple organ dysfunction (MODS), and dysfunction of the blood system (72.3%), liver (71.1%), respiratory system (53.0%) and CNS (37.3%) were common. By the end of follow-up, 40 cases (48.2%) survived, 38 cases (45.8%) died, and 5 cases (6.0%) were lost to follow-up. CNS dysfunction was a risk factor (HR=3.358, 95%CI: 1.445-7.803, P=0.005) and blood purification was a protective factor (HR=0.362, 95%CI: 0.179-0.730, P=0.005) affecting the prognosis of children. The mortality of CNS dysfunction group was statistically higher than that of non-CNS dysfunction group (74.2% vs 28.8%) (P<0.001); The mortality of blood purification group was statistically lower than that of non-blood purification group (31.0% vs 61.0%) (P=0.010).

Severe HPS in children was dangerous and had a poor overall prognosis. CNS dysfunction was a risk factor for death. Blood purification could significantly improve the prognosis and improve the survival rate of children.

To construct the geometric model of the pelvic floor by a two-dimensional equivalent mechanics method, and to explore the effect of the shape and position of pelvic floor organs and tissues on the biomechanical properties of the pelvic floor under different abdominal pressure.

A 28-year-old healthy and symmetrical married infertile female volunteer was included. The pelvic floor tissue was scanned in the supine position using a 3.0T magnetic resonance scanner (Philips Company, Holland). Based on the method of magnetic resonance imaging (MRI) two-dimensional parameter measurement and computer aided design, the geometric model and finite element model of the female pelvic floor were established, and the biomechanical characteristics of the pelvic floor support system under different abdominal pressure were analyzed.

In this study, four different working conditions of the pelvic floor force were simulated under 60, 99, 168, and 208 cmH₂O (1 cmH₂O=0.098 kPa) abdominal pressure loads. The trend was as follows: under the abdominal pressure load, the retrograde flexion of the uterus occurred, the cervical, the middle and upper vaginal segment and the levator anus muscle had the characteristic change of mechanical axial direction pointing to the sacrum and coccyx, and the deformation of the levator anus muscle in the horizontal direction was greater than that in the vertical direction. With the increase of the abdominal pressure, the maximum stress values of the pelvic floor whole system of healthy subjects under four different working conditions were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, respectively, and the maximum displacement values were 10, 14, 21 and 25 mm, respectively. The maximum stress values of the cervical and vaginal middle and upper segment were 0.111 7, 0.161 8, 0.250 6, and 0.304 1 MPa, respectively, and the maximum displacement values were 3, 6, 9, and 11 mm, respectively. The maximum stress of the perineal body was 0.063 4, 0.119 6, 0.235 2, and 0.288 0 MPa, and the maximum displacement was 1, 2, 4, and 5 mm. The maximum stress values of the levator anus muscle were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, and the maximum displacement values were 2, 4, 7, and 8 mm, respectively. The maximum stress and maximum displacement of pelvic organs increased with the increase of the abdominal pressure under different working conditions. The stress axial relationship of normal female pelvic floor was that the middle and upper segment of uterus and vagina mainly acted on the sacrococcyx and the levator anus muscle, and the lower vaginal segment acts on the perineal body.

The two-dimensional equivalent mechanical modeling and finite element analysis of the female pelvic floor system can accurately reflect the biomechanical characteristics of the female pelvic floor, and the resultant stress direction of the pelvic organs points to the sacrum and coccyx. The sacrum and coccyx, levator anus and perineal body play important stress supporting roles in the pelvic floor system.

To evaluate the occurrence and recovery of adverse drug reactions (ADRs) of preventive treatment in the elderly population with latent tuberculosis infection (LTBI).

A total of 2 583 elderly patients with LTBI were recruited in Zhongmu, Henan Province from July 1 to October 17, 2015. Face-to-face surveys and physical examinations were used to obtain the basic information of the participants, and the body mass index (BMI) was calculated. Fasting venous blood was collected from the participants for blood biochemical and routine blood tests. The random numbers were generated by Excel 2010, and the participants were divided into group A (1 284 cases) and group B (1 299 cases) by simple randomization. Both group A and group B received combination treatment of isoniazid and rifapentine. Group A was treated for 8 weeks with weekly doses of isoniazid at 15 mg/kg and 900 mg for those with body weight ≤50 and>50 kg, respectively, and the doses of rifapentin were 750 and 900 mg, respectively. Group B was treated twice a week for 6 weeks, the doses of isoniazid in patients with body weight ≤50 and>50 kg were [600-(50-body weight)×15] (rounded up) and 600 mg, respectively, and the doses of rifapentin were 600 and 450 mg, respectively. During the treatment period, doctors observed, inquired about and recorded symptoms related to ADRs, and blood biochemical and routine blood tests were performed at 4 weeks after taking the drug, the end of the treatment, and 3 months after the end of the treatment. The patients with ADRs were treated accordingly by severity. The ADRs and graded treatment outcomes of LTBI patients in group A and group B were compared.

The age［M（Q₁，Q₃）］of the participants was 60 (55,65) years old, and 54.7% (1 412/2 583) were males. There were no statistical differences in age, gender, BMI and baseline biochemical indexes between groups A and B (all P values>0.05). The incidence of ADRs in group A and group B were 18.5% (237/1 279) and 16.3% (209/1 279), respectively, and those with alanine aminotransferase (ALT)≥5 ULN accounted for 0.8% (7/931) and 1.1% (11/987), aspartate aminotransferase (AST)≥5 ULN accounted for 0.3% (3/931) and 0.3% (3/987), respectively, and there were no statistically significant differences (all P values>0.05). There were 7 and 11 patients with ALT≥5 ULN in group A and group B, respectively, and 3 patients with AST≥5 ULN for each group, respectively. After treatment, except for 2 patients with ALT≥5 ULN in group B, ALT and AST levels in all the other patients returned to normal. There were 15 and 10 patients with abnormal white blood cell count in group A and group B, respectively, and 10 and 9 patients returned to normal after treatment.

LTBI preventive treatment has a high incidence of adverse drug reactions, but it can be effectively controlled through active monitoring and graded management.

To evaluate the efficacy and safety of omalizumab in patients with refractory allergic asthma using meta-analysis.

We searched databases including PubMed, Web of Science, Embase and the website of ClinicalTrials. gov registry for randomized controlled trials (RCTs), using the search terms: ("anti-IgE" OR "anti-immunoglobulin E" OR "anti-IgE antibody" OR "omalizumab" OR "rhuMAb-E25" OR "Xolair") AND ("allergic asthma"). The time was up to September 19th 2020. Review Manager 5.4 software and Stata16 software were used to calculate pooled RR or WMD, perform heterogeneity test, and assess publication bias.

Fifteen RCTs with 6 316 patients in total (omalizumab, n=3 469; placebo, n=2 847) met our selection criteria. Comparing with placebo, omalizumab reduced the risk of asthma exacerbations during both stable-inhaled corticosteroid (ICS) phase (RR=0.69, 95%CI: 0.63-0.75, P<0.001; I²=39.0%, P=0.090) and ICS-reduction phase (RR=0.55, 95%CI: 0.46-0.66, P<0.001; I²=41.0%, P=0.180), reduced emergency visits (RR=0.53, 95%CI: 0.38-0.73, P<0.001; I²=0, P=0.420), made a significant reduction in dosage of ICS (RR=1.35, 95%CI: 1.25-1.45, P<0.001; I²=22.0%, P=0.280) and even withdrew from ICS completely (RR=1.80, 95%CI: 1.41-2.31, P<0.001; I²=57.0%, P=0.070). Omalizumab significantly improved asthma-related quality of life (RR=1.81, 95%CI: 1.51-2.17). The use of rescue bronchodilators was significantly reduced in the omalizumab group (RR=0.78, 95%CI: 0.67-0.92) but there was no significant difference in the dosage of rescue bronchodilators (puff per day) (WMD=-0.32, 95%CI: -0.77-0.13). Patients taking omalizumab did not increase the frequency of any adverse events (RR=1.01, 95%CI: 0.98-1.03) and serious adverse events (RR=0.89, 95%CI: 0.74-1.06).

Omalizumab is an ideal adjunctive treatment for refractory allergic asthma with good efficacy and safety. Further randomized controlled trials are needed to determine the appropriate duration of treatment.

The data of 33 patients with adult-onset still′s disease (AOSD)-associated macrophage activation syndrome (MAS) were retrospectively collected from January 2013 to December 2020 in Peking Union Medical College Hospital. Hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, macrophage activation syndrome/juvenile idiopathic arthritis (MS-Score) and hemophagocytic syndrome diagnostic score (HScore) were used to diagnose AOSD-associated MAS, respectively. The time of diagnosis of AOSD-associated MAS by MS-Score was 19.0 (4.5, 31.0) days [M (Q₁,Q₃)] earlier than by HLH-2004 criteria, and 13.5 (0.5, 21.5) days earlier than by HScore (both P<0.05). The difference was not statistically significant between the time of diagnosis of AOSD-associated MAS by Hscore and by HLH-2004 criteria (P>0.05). There was significant difference among the three criteria (P<0.001). MS-Score can be used to diagnose AOSD-associated MAS earlier than HLH-2004 criteria, while the timeliness of HScore is not certain.

The data of 18 patients with allergic bronchopulmonary aspergillosis (ABPA) who received aspergillus fumigatus-specific IgG detection from 2015 to 2021 in Peking University Third Hospital were retrospectively analyzed. Among them, 11 were male and 7 were female, aged 18-79 years. All patients had a history of asthma or symptoms of cough and asthma, and aspergillus fumigatus-specific IgE was positive; 16 patients had total serum IgE>500 U/ml, of which 13 patients had total serum IgE>1 000 U/ml. Among other diagnostic indicators, peripheral blood eosinophils were >0.5×10⁹/L in 16 cases; lung CT showed bronchiectasis in 15 cases; serum aspergillus fumigatus-specific IgG was positive (>120 AU/ml) in 10 cases. There was no significant difference in serum total IgE level, peripheral blood eosinophil count, and bronchiectasis ratio between positive and negative cases of aspergillus fumigatus-specific IgG (all P>0.05). In this study, the positive rate of aspergillus fumigatus-specific IgG in patients with ABPA was more than 50%, which has auxiliary value in the diagnosis of ABPA.

Calciphylaxis is a rare disease with severe pain and high-mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies. The occurrence of calciphylaxis in end stage kidney disease (ESKD) patients is known as calcific uremic arteriolopathy (CUA), which is characterized histologically by dermal microvessel calcification, intimal fibroplasia and microthrombosis. Here we innovatively treated a severe CUA patient with human amnion-derived mesenchymal stem cells (hAMSCs). A 34-year-old uremic woman was presented with progressive, painful malodorous ulcers in buttocks and mummified lower limbs. Skin pathological features supported the diagnosis of calciphylaxis. The patient was refractory to conventional multidisciplinary symptomatic therapies. With the approval of our hospital ethics committee, she was treated with hAMSCs including intravenous and local intramuscular injection, and external application of hAMSC culture supernatant to the wound area. During 15-month follow-up, the patient had regeneration of skin and soft tissues, with improved blood biochemical, inflammatory, mineral and bone metabolic indices and immunoregulation effects. After 15-month hAMSC treatment, the score of pain visual analog scale (VAS) decreased from 10 to 0, Bates-Jensen wound assessment tool (BWAT) score decreased from 65 to 13, and wound-quality of life (Wound-QoL) questionnaire score decreased from 68 to 0. We propose that hAMSC treatment is promising for CUA patients. The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, modulating adverse inflammatory and immunologic responses, promoting re-epithelialization and restoring skin integrity.

This article reports the diagnosis and treatment of a 28-year-old female patient with intestinal obstruction, intestinal ulcer, stenosis and recurrent hematochezia after chronic constipation. The patient's condition was dangerous, complicated and prolonged, and finally, through multidisciplinary cooperative diagnosis and treatment, surgery and pathology confirmed that it was Hirschsprung's disease. For patients with chronic constipation or dynamic intestinal obstruction with young onset, we should be alert to the possibility of congenital developmental abnormalities such as Hirschsprung's disease and its related diseases. It is necessary to make full differential diagnosis to avoid misdiagnosis and mistreatment. Barium enema, CT or anorectal manometry may provide clues for diagnosis and treatment. Hirschsprung's disease is relatively rare, and can be secondary to bleeding of intestinal ulcers or co-infection, resulting in dramatic changes in the condition. It is necessary to combine the patient's basic intestinal condition with differential diagnosis, and the clinical, imaging and pathology departments should fully communicate and cooperate in multiple disciplines to formulate a detailed diagnosis and treatment plan to ensure accurate treatment.

Patients with non-small cell lung cancer (NSCLC) have a high incidence and poor prognosis of brain metastasis. In recent years, immune checkpoint inhibitors (ICIs) have shown good antitumor activity in the treatment of patients with NSCLC brain metastases. At the same time, the continuous improvement of radiotherapy and medical treatment level has prolonged the survival time of patients with brain metastasis of lung cancer. This article mainly reviews the research progress of combination therapy of ICIs in patients with NSCLC brain metastasis, disease outcome and adverse reactions, and summarizes and analyzes previous clinical studies from four aspects: combination radiotherapy, combination chemotherapy, combination antiangiogenic therapy and double immunotherapy. Some retrospective studies have shown that combination therapy may bring survival benefits and controllable adverse reactions, indicating that combination immunotherapy may be one of the development trends of tumor treatment in the future.

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.