Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study.

BACKGROUND: Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, has shown encouraging anti-tumour activity in heavily pre-treated patients with relapsed or refractory peripheral T-cell lymphoma in a phase 1 study (JACKPOT8 Part A). Here, we report the full analysis of a phase 2 study, in which we assessed the anti-tumour activity of golidocitinib in a large multinational cohort of patients. METHODS: We did a single-arm, multinational, phase 2 trial (JACKPOT8 Part B) in 49 centres in Australia, China, South Korea, and the USA. Eligible patients were adults (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were given oral golidocitinib 150 mg once daily until disease progression or other discontinuation criteria were met. The primary endpoint was the CT-based objective response rate, assessed by an independent review committee (IRC) per Lugano 2014 classification. The activity analysis set included all patients who received at least one dose and whose pathological diagnosis of peripheral T-cell lymphoma had been retrospectively confirmed by a central laboratory and who had at least one measurable lesion at baseline assessed by IRC. The safety analysis set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04105010, and is closed to accrual and follow-up is ongoing. FINDINGS: Between Feb 26, 2021, and Oct 12, 2022, we assessed 161 patients for eligibility, of whom 104 (65%) were enrolled and received at least one dose of study drug; the activity analysis set included 88 (85%) patients (median age 58 years [IQR 51-67], 57 [65%] of 88 were male, 31 [35%] were female, and 83 [94%] were Asian). As of data cutoff (Aug 31, 2023; median follow-up was 13·3 months [IQR 4·9-18·4]), per IRC assessment, the objective response rate was 44·3% (95% CI 33·7-55·3; 39 of 88 patients, p<0·0001), with 21 (24%) patients having a complete response and 18 (20%) having a partial response. In the safety analysis set, 61 (59%) of 104 patients had grade 3-4 drug-related treatment-emergent adverse events. The most common grade 3-4 drug-related treatment-emergent adverse events were neutrophil count decreased (30 [29%]), white blood cell count decreased (27 [26%]), lymphocyte count decreased (22 [21%]), and platelet count decreased (21 [20%]), which were clinically manageable and reversible. 25 (24%) patients had treatment-related serious adverse events. Deaths due to treatment-emergent adverse events occurred in three (3%) patients: two (2%) due to pneumonia (one case with fungal infection [related to golidocitinib] and another one with COVID-19 infection) and one (1%) due to confusional state. INTERPRETATION: In this phase 2 study, golidocitinib showed a favourable benefit-risk profile in treating relapsed or refractory peripheral T-cell lymphoma. The results of this study warrant further randomised clinical studies to confirm activity and assess efficacy in this population. FUNDING: Dizal Pharmaceutical.

Orelabrutinib for the treatment of relapsed or refractory marginal zone lymphoma: A phase 2, multicenter, open-label study.

Marginal zone lymphoma (MZL) is an indolent type of non-Hodgkin lymphoma that develops through pathological B cell receptor signaling. Orelabrutinib, a new-generation oral small molecule Bruton's tyrosine kinase inhibitor, was evaluated in relapsed/refractory (r/r) MZL patients. Previously treated r/r MZL patients received orelabrutinib 150 mg once daily in a phase 2, multicenter, single-arm study conducted in China. The primary endpoint was overall response rate (ORR) assessed by an Independent Review Committee (IRC) based on the Lugano 2014 classification. Other efficacy, safety, and pharmacokinetic profiles were evaluated as secondary outcome measures. A total of 111 patients were enrolled, of which 90 patients had MZL confirmed by central pathology review, who were mainly with extra-nodal MZL of mucosa-associated lymphoid tissue (MALT, 46.7%) and nodal MZL (35.6%). The majority had late-stage disease, with stage IV accounting for 75.6%. After a median follow-up duration of 24.3 months, the IRC-assessed ORR was 58.9% (95% confidence interval [CI], 48.0-69.2), with rates of complete response and partial response being 11.1% and 47.8%, respectively. The IRC-assessed median duration of response was 34.3 months, and the IRC-assessed median progression-free survival (PFS) was not reached with a 12-month PFS rate of 82.8% (95% CI, 72.6-89.5). The rate of overall survival at 12 months was 91.0% (95% CI, 82.8-95.4). Common all-grade treatment-related adverse events (TRAEs) included anemia (27.9%), neutrophil count decrease (23.4%), white blood cell count decrease (18.0%), platelet count decrease (17.1%), blood present in urine (16.2%), rash (14.4%), and upper respiratory tract infection (10.8%). Thirty-four patients (30.6%) experienced grade 3 or higher TRAEs. Serious TRAEs occurred in 18 patients (16.2%), of which pneumonia (5.4%) was the most common. Seven patients (6.3%) discontinued orelabrutinib due to TRAEs. Orelabrutinib demonstrated high response rates with durable disease remission and was well tolerated in Chinese patients with r/r MZL.

Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p < 0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.

Expression and Clinical Value of Eukaryotic Translation Elongation Factor 1A1 (EEF1A1) in Diffuse Large B Cell Lymphoma.

BACKGROUND: The eukaryotic translation elongation factor 1A1 (EEF1A1) participates in protein translation and has been reported to be involved in tumor progression such as hepatocellular carcinoma. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of EEF1A1 in DLBCL and to analyze its relationship with prognosis. METHODS: We reviewed medical records of DLBCL patients in our hospital and evaluated their expression level of EEF1A1 in tumor tissues using immunohistochemical (IHC) assay. The Chi-square method was used for correlation analysis. The Kaplan-Meier method with Log rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis. Cellular and mice models were introduced to validate its oncogenic role. RESULTS: EEF1A1 expression in tumor cells was higher in certain DLBCL cases. Patients with higher EEF1A1 expression were more likely to have advanced tumor stage and poorer 5-year overall survival (OS) rates. EEF1A1 expression in tumor cells was an independent risk predictor for OS (P < 0.05). Cellular assays demonstrated that EEF1A1-shRNA significantly inhibited lymphoma cell proliferation. The study of xenografts further verified the effect of EEF1A1-shRNA on suppressing tumor growth in vivo. CONCLUSION: EEF1A1 positivity predicts short survival in DLBCL patients. For patients with higher EEF1A1 expression, more strategy such as anti-EEF1A1 antibody treatment should be developed.

Upregulation of fatty acid synthase in MYC and BCL-2 double-expressor lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common and heterogeneous lymphoid malignancy. The subtype with MYC and BCL-2 double-expressor lymphoma (DEL) was defined by its aggressive nature and poor survival outcome. Therefore, the development of effective therapies for the DEL subtype is imperative. Fatty acid synthase (FASN) activity is associated with altered lipid metabolism and aberrant protein translation in DLBCL. However, the inter-regulation of these key processes is not fully determined in DEL. In the present study, the clinical and biological impact of FASN was investigated in the DEL subtype. Initially, FASN expression levels were analyzed from a patient cohort and the data indicated that the highest FASN expression was noted in DEL tissues compared with that noted in the DLBCL and reactive lymphoid hyperplasia tissues. Patients with DEL with combined high-FASN expression indicated poorer EFS outcomes than the rest of the patients. In vitro data indicated that FASN was overexpressed in SU-DHL-2 and U2932 cells. Silencing FASN decreased cell growth and promoted cell apoptosis by modulating the pERK/BCL-2 signaling pathway. In conclusion, the present study indicated that FASN was overexpressed in DEL and that its expression was associated with poor survival outcomes. Furthermore, the data demonstrated that FASN regulated the biological function via the pERK/BCL-2 signaling pathway. FASN serves a critical role in the progression of DEL and its expression may be associated with the development to a more aggressive phenotype of DLBCL. Therefore, it may be considered a potential therapeutic target for DLBCL.

YF-H-2015005, a CXCR4 Antagonist, for the Mobilization of Hematopoietic Stem Cells in Non-Hodgkin Lymphoma Patients: A Randomized, Controlled, Phase 3 Clinical Trial.

Background: YF-H-2015005, a novel CXCR4 antagonist, has been proven to increase the quantities of circulating hematopoietic stem cells (HSCs), which results in an adequate collection of HSCs in non-Hodgkin lymphoma (NHL) patients. Methods: This was a multicenter, double-blind, randomized (1:1), placebo-controlled phase III clinical trial. All patients received granulocyte colony-stimulating factor (G-CSF) for up to 8 consecutive days. YF-H-2015005 or placebo was administrated on the evening of day 4 and continued daily for up to 4 days. Apheresis was conducted 9-10 h after each dose of YF-H-2015005 or placebo. The primary endpoint was the proportion of NHL patients procuring ≥5 × 106/kg CD34+ HSCs within ≤4 apheresis sessions. Results: In total, 101 patients with NHL were enrolled. The proportions of patients achieving primary endpoint were 57 and 12% in YF-H-2015005 and placebo groups, respectively (P < 0.001). Moreover, a higher proportion of YF-H-2015005-treated patients reached a minimum target collection of ≥2 × 106/kg CD34+ HSCs in ≤4 apheresis days compared to placebo-treated patients (86 vs. 38%, P < 0.001). Furthermore, the median time to collect ≥2 or 5 × 106/kg CD34+ HSCs were 1 and 3 days in YF-H-2015005-treated patients, but 4 days and not reached in placebo-treated patients, respectively. No severe treatment emergent adverse events were observed in both YF-H-2015005 treatment and placebo groups. Conclusions: YF-H-2015005 plus G-CSF regimen was a tolerable combination with high efficacy, which might be used to rapidly mobilize and collect HSCs in NHL patients.

Efficacy and safety of geptanolimab (GB226) for relapsed or refractory peripheral T cell lymphoma: an open-label phase 2 study (Gxplore-002).

BACKGROUND: Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. METHODS: We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. RESULTS: Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30-22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2-51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. CONCLUSIONS: In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. TRIAL REGISTRATION: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.

Efficacy and Safety of the Biosimilar IBI301 Plus Standard CHOP (I-CHOP) in Comparison With Rituximab Plus CHOP (R-CHOP) in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): A Randomized, Double-Blind, Parallel-Group, Phase 3 Trial.

INTRODUCTION: Patients with diffuse large B-cell lymphoma (DLBCL) have limited access to rituximab. IBI301 is a recombinant chimeric murine/human anti-CD20 monoclonal antibody and is a candidate biosimilar to rituximab. This study aimed to assess the therapeutic equivalence of IBI301 and rituximab in previously untreated patients with diffuse large B-cell lymphoma (DLBCL). METHODS: This multicenter, randomized, double-blind, parallel-group, phase 3 trial compared IBI301 and rituximab, both plus the chemotherapy of doxorubicin, cyclophosphamide, vindesine, and prednisone (CHOP), was conducted in 68 centers across China. Eligible patients with untreated CD20 positive (CD20+) DLBCL randomly received IBI301 (375 mg/m2) plus the standard CHOP or rituximab (375 mg/m2) plus the standard CHOP for six cycles of a 21-day cycle. The primary end point was the overall remission rate (ORR). Efficacy equivalence was defined if 95% CIs for the ORR difference between the two groups were within a ± 12.0% margin. RESULTS: Between August 22, 2016, and September 5, 2018, 419 patients were randomly allocated into the IBI301 group (N = 209) and rituximab group (N = 210). In the full analysis set, the ORR was 89.9% and 93.8% in the IBI301 and rituximab groups, respectively, and the ORR difference was -3.9% (95% CI - 9.1%-1.3%), falling within a ± 12.0% margin. The occurrences of treatment-emergent adverse events (TEAEs) (100% vs. 99.0%) and AEs of grade ≥ 3 (87.1% vs. 83.3%) were similar in the two groups (P > 0.05). CONCLUSIONS: IBI301 had a non-inferiority efficacy and a comparable safety compared with rituximab. IBI301 plus CHOP could be suggested as a candidate treatment regimen for untreated patients with CD20+ DLBCL. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov (NCT02867566).

Current management of chemotherapy-induced neutropenia in adults: key points and new challenges: Committee of Neoplastic Supportive-Care (CONS), China Anti-Cancer Association Committee of Clinical Chemotherapy, China Anti-Cancer Association.

Chemotherapy-induced neutropenia (CIN) is a potentially fatal and common complication in myelosuppressive chemotherapy. The timing and grade of CIN may play prognostic and predictive roles in cancer therapy. CIN is associated with older age, poor functional and nutritional status, the presence of significant comorbidities, the type of cancer, previous chemotherapy cycles, the stage of the disease, specific chemotherapy regimens, and combined therapies. There are many key points and new challenges in the management of CIN in adults including: (1) Genetic risk factors to evaluate the patient's risk for CIN remain unclear. However, these risk factors urgently need to be identified. (2) Febrile neutropenia (FN) remains one of the most common reasons for oncological emergency. No consensus nomogram for FN risk assessment has been established. (3) Different assessment tools [e.g., Multinational Association for Supportive Care in Cancer (MASCC), the Clinical Index of Stable Febrile Neutropenia (CISNE) score model, and other tools] have been suggested to help stratify the risk of complications in patients with FN. However, current tools have limitations. The CISNE score model is useful to support decision-making, especially for patients with stable FN. (4) There are still some challenges, including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN. In view of the current reports, our group discusses the key points, new challenges, and management of CIN.

A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma.

PURPOSE: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. EXPERIMENTAL DESIGN: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). RESULTS: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. CONCLUSIONS: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study.

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

Prognostic and predictive value of a microRNA signature in adults with T-cell lymphoblastic lymphoma.

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

[Preliminary result of multi-center clinical trial on the docetaxel, 5-Fu and DDP in the treatment of advanced, recurrent or metastatic nasopharyngeal carcinoma].

OBJECTIVE: This clinical study was designed to evaluate the efficacy and toxicity of the combined regimen of docetaxel, 5-Fu and DDP (TPF) in the treatment of advanced or relapsed nasopharyngeal carcinoma (NPC). METHODS: Fifty-six patients with newly diagnosed or recurrent/metastatic NPC following chemotherapy or radiotherapy were enrolled. Both docetaxel and DDP were administered intravenously for 6 hours at the dose of 70 mg/m2 on D1. 5-Fu was given at a dose of 400-500 mg/m2 for 6 hours from D1 to D5. Dexamethasone was routinely administered before injection of docetaxel. This combination was repeated every 3 to 4 weeks, and continued for 4-6 cycles or until PD for the responders. RESULTS: Fifty-one (91.1%) patients were evaluable for response assessment. The response rate for whole group was 72.5% (37/51) with a CR rate of 9.8% (5/51). The stable disease accounted for 17.6% (9/51). There were 17(30.4%) chemotherapy-naïve patients. The overall response rate in those was 82.4% with a CR rate of 29.4%. However, the response rate for previously treated patients was 64.7% without CR. Twelve patients had progressed disease, including 5 (8.9%) died of disease progression with a median follow-up of 11 month (ranged from 1 to 19 months). Totally, 196 courses of chemotherapy were administered. The major toxicity was myelosupression, nausea/vomiting. The incidence of leucopenia was 48% with 22.2% of these in NCI grade II or IV. But only 2 patients (3.6%) experienced leucopenia with a fever. Other mild toxicities including alopecia, asthenia, mucositis and diarrhea were also observed. CONCLUSION: Our preliminary outcome shows docetaxel, 5-Fu and DDP combination is effective and safe for the patients with advanced or relapsed nasopharyngeal carcinoma. But further clinical study is warranted.

High concentration of miR-133 is a useful marker for the diagnosis of lymphoma- associated hemophagocytic syndrome.

BACKGROUND: Lymphoma associated hemophagocytic syndrome (LAHS) is one of the major adult secondary hemophagocytic lymphohistiocytosis (HLH). Early diagnosis and treatment contribute to improved outcome. No enlarge lymph nodes can often delay the diagnosis of underlying lymphoma. OBJECTIVE: To find out criteria distinguishing LAHS from HLH induced by benign diseases. METHODS: clinical characteristic and laboratory feature of 31 patients with HLH (10 benign disease-associated HLH and 21 LAHS) were analyzed retrospectively. RESULTS: No significantly differences were observed in the levels of LDH, IL-6, IL-10, TNF-α; however, the level of CRP (C reactive protein) and the mean level of sIL-R (soluble interleukin-2 receptor) were higher in patients with LAHS than those with benign disease associated disease associated HLH while ferritin levels were higher in benign disease associated HLH than in LAHS. Consequently, the serum sIL-2R/ferritin ratio of patients with LAHS was markedly higher than that of patients with benign disease associated HLH (0.33 ± 0.23 vs 5.82 ± 3.26, P= 0.0001). In addition, we found out that the mean level of miR-133 (microRNA-133) was significant higher in LAHS than in benign disease associated HLH (18.83 ± 10.44 vs 5.82 ± 3.26, P⩽ 0.0001). CONCLUSION: Serum miR-133 is a new very useful marker for diagnosing of LAHS, but it need further confirmation by further clinical studies.