Qing-Xian Bai

Increased expression of TIGIT on CD4+ T cells ameliorates immune-mediated bone marrow failure of aplastic anemia.

Aplastic anemia (AA) is an autoimmune disease in which T cell activation is suspected to play an important role. T cell immunoglobulin and ITIM (immunoreceptor tyrosine‐based inhibition motif) domain (TIGIT) is an inhibitory receptor, which exhibits inhibitory functions on the immune response. However, its role in AA has not been clearly determined. In the current study, we showed that the frequency of TIGIT‐positive CD4+ T cells was reduced in the vast majority of AA patients (85%, 17/20). In TIGIT‐silenced human CD4+ T cells, stimulation of agonistic anti‐TIGIT monoclonal antibody significantly facilitated cell proliferation, increased production of IL‐2 and IFN‐γ, and inhibited production of IL‐10. However, in TIGIT‐overexpressed human CD4+ T cells, cell proliferation and the production of IL‐2, IFN‐γ, and TNF‐α were significantly hindered; in contrast, the secretion of IL‐10 was improved. RT‐PCR and Western blotting showed that T‐bet expression in human CD4+ T cells was significantly decreased by TIGIT overexpression, but only slightly altered by TIGIT knockdown. In mouse models, lentivirus‐mediated TIGIT‐overexpressed CD4+ T cell transfer significantly rescued the decreased red blood cell count, attenuated the increase in serum INF‐γ and TNF‐α levels, and lengthened the median survival time. The mRNA levels of CD34, stem cell factor (SCF), and granulocyte/macrophage‐colony‐stimulating factor (GM‐CSF) in bone marrow mononuclear cells were also up‐regulated. In conclusion, increased expression of TIGIT could inhibit the function of CD4+ T cells in vitro and ameliorate immune‐mediated bone marrow failure of AA in vivo providing a new potential strategy for the treatment of AA. J. Cell. Biochem. 115: 1918–1927, 2014.

Assay of AVP, CRP, and LPS in leukemia

The genesis and development of tumor are closely connected with immune system and neuroendocrine system. To investigate the changes of neuroendocrine and immune system in leukemia patients and their probable connection with leukemia, we studied five groups of patients including leukemia patients with normal temperature, leukemia patients with high temperature and infection (high‐leukocyte count group and low leukocyte count group), general patients with fever and healthy Chinese adult blood donors as control group. We determined their blood cell counts by blood count meter, determined their arginine vasopressin (AVP) levels in blood plasma by radioimmunoassay and their cross‐reacting protein (CRP), and lipopolysaccharide (LPS) levels by immunoturbidimetry. Then we studied the difference and association among these indexes. Our results revealed a significant increase of AVP, LPS, and CRP levels in the blood of leukemia patients with normal temperature vs. normal people; Individual leukemia patients had high AVP levels although they had normal LPS and CRP levels; In the group of leukemia patients with high temperature and low leukocyte counts, the CRP level is significantly higher than some of other groups, while there was no significant increase in its AVP level. We conclude that no matter the temperature is normal or not, there were always neuroendocrine disturbance, inflammation, and inapparent infection in leukemia patient; To the leukemia patients with low leukocyte counts, the relationship between inflammation and neuroendocrine is more complicated.

A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T‐cell lymphoma, nasal type: a multicenter trial in Northwest China

The nasal type of extranodal natural killer/T‐cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol‐asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T‐cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2‐year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression‐free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment‐related deaths. These results will require confirmation in larger prospective trials.

Sodium Salicylate—Triggered Apoptosis in HL-60 Cells Depends on Caspase-8 Activation

For investigation of the killing and proapoptotic effects of sodium salicylate (Na-Sal) on HL-60 cells, the cytotoxic activity of Na-Sal was measured by means of MTT assay. Apoptosis was identified and analyzed with the help of transmission electron microscopy, annexin V staining, and DNA gel electrophoresis, and the association of caspase-8 activation with apoptosis was determined with the specific protease inhibitor IETD-fmk. After exposure of HL-60 cells to increasing concentrations of NaSal (0.5,1,3,5, and 7 mmol/L) for 24 hours, the mean cell viability gradually dropped to 92%, 83%, 68%, 50%, and 42%. With treatment of target cells with 5-mmol/L (IC50) Na-Sal for 6,12, 24, or 36 hours, the mean cell survival tapered to 91%, 81%, 48%(P < .05 versus control), and 14%(P < .05 versus control). Again incubated with 5-mmol/L Na-Sal for 12 or 24 hours, HL-60 cells displayed clear early or late signs of apoptosis, including (1) notable enhancement of phosphatidylserine externalization, (2) cell shrinkage, membrane blebbing, and eventual disintegration into numerous apoptotic bodies, and (3) formation of ladder DNA. The viability of HL-60 cells increased significantly during 24 or 36 hours of coculture with 100-μmol/L IETD-fmk in combination with 5-mmol/L Na-Sal compared with the viability when 5-mmol/L Na-Sal was used alone(P < .05). Moreover, the target cells showed a considerable decrease in phosphatidylserine exposure and DNA fragmentation after coincubation for 12 or 24 hours performed as described above. The findings presented herein strongly suggest that Na-Sal can exert potent killing and proapoptotic activity against HL-60 cells, and this effect appears to depend on caspase-8 activation.

Successful Treatment of Liver Aspergilloma by Caspofungin Acetate First-Line Therapy in a Non-Immunocompromised Patient

Aspergillosis remains to be a life-threatening complication in immunocompromised patients. However, Aspergillus infection can be observed in non-immunocompromised individuals in rare cases. We report a case of liver aspergilloma in a chronic aplastic anemia patient under relatively intact immune status. Therapeutic strategy for this rare condition was extensively discussed and caspofungin acetate single agent first-line therapy was applied after careful consideration. Encouraging clinical and radiologic improvements were achieved in response to the antifungal salvage. Our long-term follow-up study also revealed a favorable prognosis. Based on this experience, we suggest caspofungin acetate as first-line therapy for treatment plans of liver aspergilloma.

Natural Killer/T Cell Lymphoma, Nasal Type: A Retrospective Clinical Analysis in North-Western China

Background: Extranodal natural killer (NK)/T cell lymphoma (ENKTL) is an aggressive non-Hodgkins lymphoma with high mortality and poor prognosis despite radiotherapy and chemotherapy. The current analysis aimed to assess the pathological features, clinical features, and prognostic indicators of ENKTL. Material and Methods: 120 ENKTL patients were analyzed for pathologic diagnosis and clinical disease manifestations from April 2007 to October 2012. Complete remission, 2-year overall survival, and progression-free survival were analyzed. Results: Compared with the nasal group, a greater percentage of patients in the non-nasal group intended to receive autologous stem cell transplantation had Epstein-Barr virus (EBV) DNA, Ann Arbor stage IV, Ki-67 expression ≥ 60%, and abnormal ferroprotein and β-microglobulin levels. The rate of complete remission in the non-nasal group was higher than that in the nasal group. The overall survival rate was 74.9% at 24 months. Patients receiving chemotherapy and radiotherapy were more likely to have disease progression compared with patients who received chemotherapy or radiotherapy alone. Conclusions: Further understanding the pathological and clinical features of ENKTL will be critical for moving forward. Ki-67, β-microglobulin, EBV DNA, and primary site prognostic indicators may be useful to stratify patients into different risk groups, to gain insight into patient-specific treatments, and to potentially improve survival.

Survival outcomes of primary cutaneous T-cell lymphoma in HIV-infected patients: a national population-based study

This study aimed to investigate clinical characteristics and survival outcomes of primary cutaneous T-cell lymphoma (CTCL) in HIV-infected and non-HIV-infected patients. All data were from the Surveillance, Epidemiology, and End Results program, 1973–2013, of the U.S. National Cancer Institute. Data of 318 HIV-infected patients and 1272 non-HIV-infected patients with primary CTCL were analyzed. Endpoints were overall survival and cancer-specific mortality. Independent variables included demographics, pre-existing malignancy, treatments, and environmental factors. Among 8823 patients with CTCL, 318 (3.60 per cent) were HIV-infected and 8505 (96.40 per cent) were not. 318 HIV-infected patients and 1272 non-HIV-infected patients selected by matching diagnosis dates were analyzed, including 941 (59.2 per cent) males and 649 (40.8 per cent) females with mean age 58.8 years. HIV-infected patients with CTCL had higher survival and significantly lower risk of overall mortality than non-HIV-infected patients (adjusted HR 0.37, 95 per cent CI 0.24 to 0.59, P<0.001). Non-HIV-infected, age and black race were significant risk factors for overall mortality. Age and race are independent risk factors for overall mortality in primary CTCL individuals, and HIV-infected status is an independent protective factor, suggesting that advanced antiretroviral therapy restores immunity and prolongs survival in HIV-infected patients with CTCL.

Distribution of lymphoid neoplasms in Northwest China: Analysis of 3244 cases according to WHO classification in a single institution

To explore the distribution of lymphoid neoplasms in Northwest China, the clinical and pathological data of lymphoma patients from 2006 to 2014 were analyzed according to the WHO classification in Xijing Hospital. Of the 3244 cases, mature B-cell neoplasms occupied 60.7%, while mature T/NK-cell neoplasms and Hodgkins lymphomas (HL) occupied 26.2% and 8.1%, respectively. The most common subtype of lymphoma was diffuse large B-cell lymphoma (35.0%), followed by extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (12.9%) and marginal zone B-cell lymphoma (7.8%). Mixed cellularity (34.0%) was the most common subtype of HL. The especially high proportion of ENKTCL was the most outstanding feature of our study in comparison to previous reports. The mean age of all lymphoid neoplasms cases was 51years and most subtypes showed male predominance, with an average male-female ratio of 1.6. Extranodal lymphomas took up about 60% of all cases and gastrointestinal tract was the most frequently involved site. In conclusion, the distribution of lymphoid neoplasms of Northwest China showed some features similar to previous reports of China and other countries, but some subtypes presented distinct features.

A Study to Compare the Efficacy and Safety of Obinutuzumab + Venetoclax versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia (CLL14)

This open-label, multicenter, randomized phase III study is designed to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax versus obinutuzumab + chlorambucil in patients with chronic lymphocytic leukemia (CLL) and coexisting medical conditions. The anticipated time on study treatment will be approximately 1 year and the follow-up period will be up to 5 years.

Optimale Mobilisierungsstrategien für den individuellen Patienten

Die autologe Stammzelltransplantation ist eine etablierte Therapie bei Patienten mit multiplem Myelom oder Lymphomen. Für einen optimalen Therapieerfolg ist eine ausreichende Stammzellmobilisierung essentiell. Ist die Mobilisierung mit dem Granulozyten-Kolonien stimulierenden Faktor (G-CSF) nach Induktionschemotherapie nicht erfolgreich, kann die Stammzellernte mit zusätzlicher PlerixaforGabe gesteigert werden. Bei einem von der Firma Sanofi gesponserten Workshop gingen Prof. Dr. Kai Hübel, Uniklinik Köln, und Dr. Patrick Wuchter, Universitätsklinikum Heidelberg, im Rahmen des COSTEM (Controversies in Stem Cell Transplantation and Cellular Therapies)-Kongresses auf aktuelle Fragen der Stammzellmobilisierung ein.