Expression and Clinical Significance of Serum sFas/sFasL in Patients with Secondary Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).@*METHODS@#From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve.@*RESULTS@#Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001).@*CONCLUSION@#Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.

Clinical analysis of secondary hemophagocytic lymphohistiocytosis complicated with capillary leak syndrome / 中华血液学杂志

Objective: To investigate the clinical characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with capillary leak syndrome (CLS) . Methods: The clinical and laboratory data of 87 sHLH patients, who were treated in our hospital between January 2015 and December 2017, were retrospectively analyzed. Depending on whether they were complicated with CLS, 21 sHLH patients were classified as the CLS-sHLH group, while 66 were classified as the non-CLS-sHLH group. The differences of clinical manifestations, laboratory tests, treatment and prognosis between the two groups were compared. Results: There was no significant difference in the etiology of sHLH between the CLS-sHLH group and the non-CLS-sHLH group (P>0.05) . The neutrophil, fibrinogen and albumin levels in the CLS-sHLH group were lower than those in the non-CLS-sHLH group, while the triacylglycerol levels were higher than those in the non-CLS-sHLH group (P<0.05) . Varying degrees of edema, weight gain, hypotension, hypoproteinemia, oliguria and multiple serous effusions were observed in the CLS-sHLH group. Among them, there were 15 patients that CLS get improved, and the medial time of improvement was 7 (5-14) days. The other 6 patients did not get remission, while they died within 6-30 days. The median overall survival of the CLS-sHLH group was lower than that of the non-CLS-sHLH group (75 days vs not reached, P=0.031) . Conclusions: There may be no correlation between the cause of sHLH and the occurrence of CLS. Severity of neutropenia, fibrinogen and albumin levels, and triglyceride levels may be accompanied for sHLH patients complicated with CLS. Patients with sHLH who complicated with CLS have a poor prognosis. Active treatment of HLH and its primary disease, reasonable fluid replacement and oxygen supply are crucial, which can effectively control disease progression.

Expression of Serum HMGB-1 in Patients with Secondary Hemo-phagocytic Lymphohistiocytosis and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression levels and clinical significance of serum high mobility group box 1 (HMGB-1) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).</p><p><b>METHODS</b>Serum HMGB-1 levels were determined by using enzyme linked immunosorbent assays (ELISA) in 51 sHLH patients and 15 healthy contrlols. Other laboratory data, including soluble interleukin-2 receptor (sCD25), white blood cells (WBC), hemoglobin (Hb), platelet (Plt), fibrinogen (FIB), lactate dehydrogenase (LDH), triglyceride (TG), alanine transaminase (ALT), aspartate aminotransferase (AST), serum ferritin (SF), C reactive protein (CRP), and blood sedimentation rate (ESR) were also collected.</p><p><b>RESULTS</b>Serum HMGB-1 levels in the newly diagnosed group were significantly higher than that in the control group (P<0.01). Serum HMGB-1 levels in the newly diagnosed lymphoma-associated HLH (LHLH) group were significantly higher than that in non-HLH group, including infection-associated HLH (IHLH) and autoimmune-associated HLH (AHLH) group (P<0.05); The serum HMGB-1 levels in the clinical remission group were significantly lower than that in the newly diagnosed group (P<0.05), however, serum HMGB-1 was not decreased significantly in the progression/relapsed group, compared with the newly diagnosed group (P>0.05). Serum HMGB-1 levels in newly diagnosed sHLH patients positively correlated with sCD25 (r=0.62, P<0.01) and ESR (r=0.55, P<0.05). The receiver operating characteristic curves (ROC) for serum HMGB-1 levels of sHLH patients and healthy controls produced a cutoff value at 15.3 µg/L, with its 90% sensitivity and 99% specificity, respectively. In addition, an optimal cutoff value for HMGB-1 was 27.4 µg/L in the patients LHLH and non-HLH (AHLH+IHLH) with 96% sensitivity and 81% specificity, separately.</p><p><b>CONCLUSION</b>Serum HMGB-1 levels possesses an important clinically significance for disease diagnosis, differential diagnosis, evaluation of nosographic activity and treatment efficacy in the patients with sHLH.</p>

Treatment of two chronic myeloid leukemia patients with V299L mutation by using nilotinib / 中国实验血液学杂志

This study was aimed to enhance clinical understanding the effect of nilotinib on CML patients with V299L mutation who were resistant to imatinib. Bone marrow specimens from 2 cases of CML with V299L mutation were collected before and after the treatment with nilotinib. ABL mutation was detected by nested reverse transcription polymerase chain reaction (PCR) followed by direct sequencing. The clinical characteristics of the two cases were analyzed. The results showed that both cases were resistant to imatinib presented V299L mutation. Out of them 1 case achieved complete haematological response (CHR) after treatment with nilotinib for 6 months and another case abstained obvious molecular response after using nilotinib for 7 month. V299L mutation of both cases was turned into negative after the treatment with nilotinib. It is concluded that the nilotinib can safely and effectively override tyrosine kinase inhibitor (TKI) resistance mediated by the V299L mutation. The safety and efficacy of nilotinib for treatment of CML patients with TKI resistance and V299L mutation are satisfactory.

Anti-human 4-1BBL monoclonal antibody stimulates the nuclear translocation of NF-κB and the co-location of 4-1BBL/CD28 isoform in U937 cells / 中国实验血液学杂志

This study was purposed to investigate the molecular mechanism of 4-1BBL reverse signals in the human acute monocytic leukemia cell line of U937. The U937 cell line was used as target cells, and stimulated by the mouse anti-human 4-1BBL monoclonal antibody 1F1. The nuclear translocation of NF-κB and the co-location of 4-1BBL and CD28i molecules in U937 cells were observed with confocal laser scanning microscopy. The protein and m-RNA expression levels of 4-1BBL and CD28i were detected by flow cytometry and RT-PCR respectively. The results showed that the significant nuclear translocation of NF-κB and co-localization of 4-1BBL and CD28i on membrane of U937 cells appeared after being stimulated by mAb1F1. It is concluded that the 4-1BBL reverse signals transduction mediating the growth of U937 cells relates with the nuclear translocation of NF-κB. CD28i may be involved in intracellular 4-1BBL reverse signaling pathways.