IL-6 and IL-10 Are Associated With Gram-Negative and Gram-Positive Bacteria Infection in Lymphoma.

To investigate the Th1/Th2 cytokine profile in patients with lymphoma during the myelosuppression stage of infection. 52 patients with gram-negative bacterial infection (G- group), 49 patients with gram-positive bacterial infection (G+ group), 51 uninfected patients with lymphoma (uninfected group) and 20 healthy controls (healthy group) were enrolled in this study. We evaluated the quantification of Th1/Th2 cytokines with flow cytometry bead assay (CBA) in the sera to explore a rapid diagnostic method to determine the type of infection and anti-infective effect. The levels of procalcitonin (PCT) were also detected simultaneously. The four groups did not differ with regard to IL-2 and IL-4 (P>0.05). The IFN-γ and TNF-α levels of patients with lymphoma were higher than those of healthy controls (P<0.05). There was significantly upregulated IL-6 and IL-10 expression in the G- group (P<0.001). A similar trend was reflected in the IL-6 of the G+ group, which was significantly increased (P<0.001). However, no significant upregulation was observed for IL-10 in the G+ group. According to the different degrees of increased IL-6 and IL-10 levels, We proposed to use the G- Bacterial Infection Cytokine Profile (G- BICP) and the G+ Bacterial Infection Cytokine Profile (G+ BICP) for the first time to differentiate between Gram-negative and Gram-positive (G-/G+) bacterial infection in adults with lymphoma in the myelosuppression stage after chemotherapy. The IL-6, IL-10 and PCT in the G- group and the IL-6, PCT in the G+ group were significantly decreased at day 4 and day 8 compared with those at day 1. IL-6 and IL-10 are closely associated with the severity and treatment efficacy in adults with lymphomas who develop infections after chemotherapy and can help distinguish between G- and G+ bacterial infections at an early stage.

The successful treatment of Enterocytozoon bieneusi Microsporidiosis with nitazoxanide in a patient with B-ALL: A Case Report.

Introduction: Enterocytozoon bieneusi (E. bieneusi) Microsporidia can cause opportunistic infections in immunocompromised patients and is also an emerging disease in these individuals. Its clinical manifestations are chronic diarrhea and severe wasting syndrome, these can be extremely debilitating and carry a significant risk of death for immunocompromised patients. Often, microsporidia cannot be confirmed immediately by routine examination and culture. Effective and available treatment options are limited for infections caused by E. bieneusi in humans. Such cases are very rare in Chinese Mainland. Case presentation: A 47-year-old male had recurrent, profuse watery diarrhea and abdominal discomfort for more than 7 months, with a fever for 5 days. Two years earlier, he received treatment with a modified BFM-90 protocol for acute B cell lymphoblastic leukemia and is currently in the final stages of maintenance therapy with oral methotrexate and mercaptopurine. The leukemia was assessed as still in remission two months ago. PET/CT showed massive peritoneal fluid accumulation and a high uptake area in the diffused peritoneum (SUVmax 12.57), suggesting tumor invasion or microbial infections. However, broad-spectrum antibacterial therapies were ineffective. Metagenomic sequencing of plasma and peritoneal fluid showed no suggestion of the existence of a tumor but instead showed a high sequence number of DNA and RNA of the Microsporidia. His albendazole treatment failed and subsequent treatment with nitazoxanide successfully resolved the infection. Conclusion: This case shows that we should consider the possibility of atypical pathogen infection in patients with hematologic malignancy who repeatedly develop unexplained diarrhea with wasting. mNGS can help rule out malignant neoplasms and diagnose infections. Our results suggest that nitazoxanide effectively treats E. bieneusi microsporidia infections.

A Real-World Observation of Eltrombopag and Recombinant Human Thrombopoietin (rhTPO) in Lymphoma Patients With Chemotherapy Induced Thrombocytopenia.

This real-world, observational study aimed to assess and compare the clinical efficacy and safety of eltrombopag with recombinant human thrombopoietin (rhTPO) in the treatment of chemotherapy induced thrombocytopenia (CIT) in patients with lymphoma. One hundred and fifty-three patients who experienced grade 3 or 4 thrombocytopenia after chemotherapy for lymphoma were enrolled, 51 of which were treated with eltrombopag, 50 with rhTPO, and 52 patients with no drug treatment were served as the control group. The lowest platelet level and mean platelet counts at Day 5, Day 7, and Day 10 were significantly higher in both the eltrombopag group (P=.041,.003,.000,.000) and rhTPO group (P=.005,.005,.000,.000) than the control, but there was no difference between treatment with eltrombopag and rhTPO. Similarly, days required for the recovery of platelet counts to ≥50×109/L and ≥75×109/L were not different between the two treatment groups but significantly higher than the control group (P <.05). Rates of bleeding and platelet transfusion were all significantly reduced in patients treated with eltrombopag (P=.031,.032) or rhTPO (P=.017,.009) when compared to the control. Treatment-related adverse events (AEs) were reported in 7 (13.7%) and 6 (12.0%) patients in the eltrombopag and rhTPO groups, respectively, all being mild and transient in nature. In conclusion, both eltrombopag and rhTPO were effective and safe in the treatment of thrombocytopenia after chemotherapy for lymphoma.

Ruxolitinib combined with doxorubicin, etoposide, and dexamethasone for the treatment of the lymphoma-associated hemophagocytic syndrome.

PURPOSE: Case reports suggest that ruxolitinib-containing treatment could increase the clinical response rate of patients with hemophagocytic syndrome (HPS). This study aimed to explore the effect of ruxolitinib-containing treatment for patients with lymphoma-associated hemophagocytic syndrome (LAHS). METHODS: This was a retrospective study of patients with LAHS hospitalized at the First Affiliated Hospital of Guangdong Pharmaceutical University between October 2017 and September 2019. Patients were treated with HLH-94 (etoposide and dexamethasone) or R-DED regimen (ruxolitinib, doxorubicin, etoposide, and dexamethasone). The clinical characteristics, treatment responses, and overall survival (OS) were compared. The patients were divided into the HLH-94 group (n = 34) and the R-DED group (n = 36). RESULTS: Compared with HLH-94, R-DED might effectively improve the clinical manifestations, including fever and splenomegaly in patients with LAHS, and control the systemic cytokine storm. The response rate at 2 weeks was 54.8% in the HLH-94 group, which was lower than in the R-DED group (83.3%) (p = 0.011). The OS was significantly prolonged in the R-DED group compared with the HLH-94 group (median, 5 vs. 1.5 months, p = 0.003). The multivariable analysis showed that lower IL-10 levels [hazard ratio (HR)] = 1.000, [95% confidence interval (CI)] 1.000-1.000, p = 0.012), R-DED regimen (HR = 0.196, 95% CI 0.084-0.457, p < 0.001), and non-NK/T-cell lymphoma (HR = 0.254, 95% CI 0.102-0.628, p = 0.003) were associated with better OS. The prognosis of patients with LAHS was generally poor. CONCLUSION: Ruxolitinib can be combined with chemotherapy in HPS. It is feasible, with no early signals of increased toxicity.

Application of blood and immunodeficiency gene detection in the diagnosis of hemophagocytic lymphohistiocytosis patients.

To investigate the value of genetic mutations in the pathogenesis and differential diagnosis of hemophagocytic lymphohistiocytosis (HLH), mutations related to blood and immune deficiency genes were analyzed in patients with HLH. Peripheral blood samples from 33 children diagnosed with HLH on the basis of the 2004 diagnostic criteria were collected, and 317 genes related to blood system diseases and 562 genes related to immunodeficiency were detected by second-generation targeted sequencing technology, bioinformatic analysis, and parental verification analysis. A total of 159 mutations related to blood system diseases and immunodeficiency were found in 33 patients, including 7 HLH-related gene mutations (UNC13D, XIAP, LYST, STX11, ITK, PRF1, and SRGN) in 12 patients. UNC13D was found in 6 patients, with the highest frequency. Two cases (6.1%, 2/33) were diagnosed as primary hemophagocytic lymphohistiocytosis (pHLH), and 6 cases (18.2%, 6/33) were diagnosed as primary immunodeficiency disease (PID) or hereditary hematopathy; the remainder were diagnosed as secondary hemophagocytic lymphohistiocytosis (sHLH). It is necessary to detect blood and immunodeficiency genes to exclude the possibility of pHLH, PID, or hereditary hematopathy associated with HLH for children.

Prognostic significance of DAPK promoter methylation in lymphoma: A meta-analysis.

We aimed to characterize the clinical significance of epigenetic loss of death-associated protein kinase (DAPK) gene function through promoter methylation in the development and prognosis of lymphoma. PubMed, Web of Science and ProQuest databases were searched for relevant studies. Twelve studies involving 709 patients with lymphoma were identified. The prognostic value of DAPK methylation was expressed as risk ratio (RR) and its corresponding 95% confidence interval (CI), while the associations between DAPK methylation and the clinical characteristics of patients with lymphoma were expressed as odd ratios (ORs) and their corresponding 95% CIs. Meta-analysis showed that the 5-year survival rate was significantly lower in lymphoma patients with hypermethylated DAPK (RR = 0.85, 95% CI (0.73, 0.98), P = 0.025). Sensitivity analysis demonstrated consistent result. However, no associations were found between DAPK methylation and clinicopathological features of lymphoma, in relation to gender (OR = 1.07, 95% CI (0.72, 1.59), P = 0.751), age (OR = 1.01, 95% CI (0.66, 1.55), P = 0.974), international prognostic index (OR = 1.20, 95% CI (0.63, 2.27), P = 0.575), B symptoms (OR = 0.76, 95% CI (0.38, 1.51), P = 0.452), serum lactate dehydrogenase (OR = 1.13, 95% CI (0.62, 2.05), P = 0.683), and BCL-2 expression (OR = 1.55, 95% CI (0.91, 2.66), P = 0.106). Lymphoma patients with hypermethylated DAPK are at risk for poorer 5-year survival rate. DAPK methylation may serve as a negative prognostic biomarker among lymphoma patients, although it may not be associated with the progression of lymphoma.

[Expression of Sema4D in patients with cerebral infarction and its clinical significance].

OBJECTIVE: To explore the expression and clinical significance of Semaphorin4D (Sema4D) mRNA in peripheral blood lymphocyte, Sema4D on platelet surface, soluble Sema4D (sSema4D) in plasma in patients with cerebral infarction. METHODS: Taking 299 patients with cerebral infarction as the case group while 195 healthy adults as the control group. The mRNA expression of Sema4D was detected by Real-time PCR, and Sema4D expression on platelet by flow cytometry, sSema4D by ELISA. Then, the expression of Sema4D on platelet surface and the concentration of sSema4D in plasma of the 195 selected patients following 2 weeks' treatment were tested. RESULTS: The expression of Sema4D mRNA significantly increased in the case group \[(2.23, 2.66)×10(4) IU/ml\] than in the control group \[(0.49, 0.53)×10(4)IU/ml\] (P < 0.01). The level of Sema4D on platelet surface in the case group (191.62 ± 46.56) significantly decreased than in the control group (303.33 ± 112.66) (P < 0.01). But the concentration of sSema4D in plasma in the case group \[(1.34 ± 0.56) µg/L\] was obviously higher than in the control group \[(0.61 ± 0.31) µg/L\] (P < 0.01). The expression of Sema4D on platelet was obviously relevant with the concentration of sSema4D in plasma in the case group with the correlation coefficient as 0.328 (P < 0.01). The expression of Sema4D on platelet obviously peaked up following 2 weeks' routine therapy in the case group, which was close to that in the control group. Meanwhile the concentration of sSema4D in plasma was downward corrected to the normal in the case group. CONCLUSION: The increased expressions and plasma levels, and reduced expressions on platelet of Sema4D in acute period, which returned to normal 2 weeks after treatment in the case group may be related to the occurrence of acute cerebral infarction, reflecting the development process of cerebral infarction.

[Clinical significance of protein Z alteration in patients with cardio-cerebral thrombotic diseases].

OBJECTIVE: To study the alteration of protein Z (PZ) in patients with cardio-cerebral thrombotic diseases, its clinical significance and relations with FX. METHODS: PZ and FX:Ag were measured by ELISA, and plasma FX:C by first stage method. In 170 patients with acute ischemic stroke (AIS), 40 acute myocardial infarction (AMI) and 60 healthy adults as contrast, PZ, FX:C and FX:Ag were measured and compared between incipience and recurrence, different ages and genders. RESULTS: In AIS and AMI groups, PZ levels decreased significantly to (940.02 +/- 229.82) microg/L and (1071.44 +/- 180.52) microg/L, respectively \[the contrast group was (2257.97 +/- 479.76) microg/L, P < 0.001\]. But FX:C and FX:Ag raised to (136.73 +/- 34.93)% and (135.54 +/- 54.39)% in AIS group; and to (139.53 +/- 29.18)%, (129.75 +/- 21.91)% in AMI group, respectively, while in the contrast group they were (94.33 +/- 22.00)% and (77.22 +/- 13.19)% (P < 0.001). In the comparative research between the AIS group, AMI group and the contrast group, PZ level was clearly found to negatively relate to the level of FX:C and FX:Ag (P < 0.001). Meanwhile, PZ level, FX:C and FX:Ag in recur-AIS group and recur-AMI group exhibited significant differences (P < 0.05) from those in the primary AIS and AMI groups, suggesting that the decrease of PZ levels reflected the pathological process of the disease. In addition, PZ level gradually decreased with the increase of age (P < 0.05), while FX:C and FX:Ag had no relations with age (P > 0.05). No correlation was found in sex with PZ level, FX:C, FX:Ag (P > 0.05). CONCLUSION: PZ level was significantly decreased in AIS and AMI patients and was negatively related to FX:C and FX:Ag. The mechanism leading to FX increase may partially related with the decreased of PZ. PZ level was different in the primary and recurrent disease and was gradually decreased with the increase of age. Lack of PZ might be a etiological factor of cardio-cerebral thrombotic diseases.