[Correlation Analysis of Peripheral Blood B Cell Count with Clinical Features and Prognosis in Patients Newly Diagnosed with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: The relationship of peripheral blood B cell count with clinical features, laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed. RESULTS: Patients were divided into low B-cell count group (B cell＜0.1×109/L, n=34) and high B-cell count group (B cell≥0.1×109/L, n=33) according to the median B cell count values. Compared with the high B cell count group, the low B cell count group had a higher proportion of patients with Lugano stage III-IV, elevated LDH, elevated ß2-MG and IPI score 3-5 and increased CRP (P =0.033, 0.000, 0.023, 0.001, 0.033). The peripheral CD3+ and CD4+ cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group (P =0.010, 0.017). After initial treatment, overall response rate (ORR) and complete remission (CR) rate in high B cell count group were significantly higher than those in low B cell count group (P =0.032, 0.013). The median follow-up time of patients was 23(2-77) months, progression-free survival (PFS) and overall survival (OS) of patients in the high B cell count group were significantly better than those in the low B cell count group (P =0.001, 0.002). Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS (HR=4.108, P =0.002; HR=8.218, P =0.006). Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS (HR=3.116, P =0.037). CONCLUSION: Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy, which is associated with poor clinical prognosis.

Clinical characteristics and immunological abnormalities of Castleman disease complicated with autoimmune diseases.

PURPOSE: To explore the clinical features and immunological mechanisms of Castleman disease (CD) complicated with autoimmune diseases (AID). METHODS: We explored the prevalence and clinical manifestations of CD complicated with AID by reviewing clinical, pathological, and laboratory data of 40 CD patients retrospectively, and then explored abnormal immune mechanisms in the co-existence of the two entities by monitoring lymphocyte subsets in peripheral blood. RESULTS: Paraneoplastic pemphigus, autoimmune hemolytic anemia, Sjogren's syndrome, myasthenia gravis, and psoriasis were found to be coexisted with CD in 9/40 (22.5%) patients with different sequence of onset. No bias in the clinical and histological type of CD was observed for the occurrence of AID. CD patients with AID were more likely to have skin and/or mucous membrane damage and pulmonary complications, and presented elevated erythrocyte sedimentation rate, hypergammaglobulinemia, and positive autoantibodies than those without AID (p < 0.05). Deregulated cellular and innate immune responses as indicated by decreased CD3+ T cells and increased natural killer cells were observed in peripheral blood of CD patients with AID (p < 0.05). UCD patients with AID were successfully treated with surgery and immunosuppressive therapy. MCD complicated by AID relieved with immunosuppressors, cytotoxic chemotherapy, and rituximab. CONCLUSION: Systemic inflammation/immunological abnormalities and organ dysfunction were associated with the occurrence of AID in CD. Impairment of cellular and innate immunity may be a candidate etiology for the coexistence of the two entities.

Thymic hyperplasia after chemotherapy in adults with mature B cell lymphoma and its influence on thymic output and CD4(+) T cells repopulation.

To investigate the thymic regenerative potential in adults accepting chemotherapy for lymphoma. The dynamics of thymic activity in 54 adults from baseline to 12 mo post-chemotherapy was analyzed by assessing thymic structural changes with serial computed tomography (CT) scans, and correlating these with measurements of thymic output by concurrent analysis of single-joint (sj) T-cell receptor excision circles (sjTREC) and CD31(+) recent thymic emigrants (RTE) in peripheral blood. Furthermore, the consequence of thymic renewal on peripheral CD4(+) T cell recovery after chemotherapy was evaluated. Time-dependent changes of thymic size and thymic output assessed by both sjTREC levels and CD31(+) RTE counts in peripheral blood were observed during and after chemotherapy. Enlargement of thymus over baseline following chemotherapy regarded as rebound thymic hyperplasia (TH) was identified in 20 patients aged 18-53 y (median 33 y). By general linear models repeated measure analysis, it was found that, patients with TH (n = 20) had a faster recovery of sjTREC levels and CD31(+) RTE counts after chemotherapy than patients with comparable age, gender, diagnosis, disease stage, thymic volume and output function at baseline but without TH (n = 18) (p = 0.035, 0.047); besides, patients with TH had a faster repopulation of both naïve CD4(+) T cell and natural regulatory CD4(+) T cell subsets than those without TH (p = 0.042, 0.038). These data suggested that adult thymus retains the capacity of regeneration after chemotherapy, especially in young adults. The presence of TH could contribute to the renewal of thymopoiesis and the replenishment of peripheral CD4(+) T cell pool following chemotherapy in adults.

Long intergenic non-coding RNA 00152 promotes tumor cell cycle progression by binding to EZH2 and repressing p15 and p21 in gastric cancer.

Long noncoding RNAs (lncRNAs) play important regulatory roles in several human cancers. Integrated analysis revealed that expression of long intergenic non-coding RNA 152 (LINC00152) was significantly upregulated in gastric cancer (GC). Further analysis in a cohort of 97 GC patients revealed that LINC00152 expression was positively correlated with tumor invasion depth, lymph node metastasis, higher TNM stage, and poor survival. Gene set enrichment analysis revealed that cell proliferation and cell cycle progression were increased in patients with high LINC00152 expression. In both GC cell lines and xenograft systems, LINC00152 overexpression facilitated GC cell proliferation by accelerating the cell cycle, whereas LINC00152 knockdown had the opposite effect. Moreover, by binding to enhancer of zeste homolog 2 (EZH2), LINC00152 promotes GC tumor cell cycle progression by silencing the expression of p15 and p21. These findings suggest that LINC00152 may play contribute to the progression of GC and may be an effective therapeutic target.

Investigating Factors Associated with Thymic Regeneration after Chemotherapy in Patients with Lymphoma.

The factors involved in thymus regeneration after chemotherapy has not been sufficiently explored. This study was aimed to identify the clinical characteristics and single-nucleotide polymorphisms in the gene (IL7R) encoding IL-7Rα associated with thymus renewal after chemotherapy in Chinese Han individuals with lymphoma. The dynamics of thymic activity in 134 adults with Hodgkin lymphoma (HL) and B cell lymphoma from baseline to 12 months post-chemotherapy were analyzed by assessing thymic structural changes using serial computed tomography scans and correlating these with measurements of thymic output by concurrent analysis of single-joint T-cell receptor excision circles (sjTREC) and CD31+ recent thymic emigrants (RTE) in peripheral blood. The association of clinical variables and IL7R polymorphisms with the occurrence of rebound thymic hyperplasia (TH) and the recovery of thymic output following chemotherapy were evaluated. Thymic regeneration was observed, with the evidence that TH occurred in 38/134 (28.4%) cases, and thymic output, assessed by CD31+ RTE numbers and sjTREC content, recovered to baseline levels within 1 year after the end of therapy. The frequencies of the T allele and TT + GT genotype of rs7718919 located in the promoter of IL7R were significantly higher in patients with TH compared with those without TH (P = 0.031 and 0.027, respectively). In contrast, no significant difference was found between two groups with respect to the distribution of allele and genotype frequencies of rs6897932. By general linear models repeated-measure analysis, rs7718919 and rs6897932 were determined to exert no significant effects on the recovery of thymic output after therapy. Univariate analysis revealed host age under 30, the diagnosis of HL, baseline thymic index and CD31+ RTE counts, and rs7718919 genotype as potential predictors for TH after chemotherapy (P < 0.05); after multivariate adjustment, only host age was independently associated with the occurrence of TH (odds ratios = 4.710, 95% confidence intervals: 1.727-12.845, P = 0.002). These findings indicate that patient age is an independent predictor for thymic regrowth after chemotherapy, which should promote awareness among physicians to make a timely diagnosis of TH in young adults and help physicians to prioritize intervention strategies for thymus rejuvenation in this population.

[Clinical Analysis of Anemia in Castleman Disease].

OBJECTIVE: This study was to explore the characteristics of anemia in Castleman disease (CD). METHODS: Clinical data were collected retrospectively to analyze the prevalence and characteristics of CD with anemia were analysed retrospectively, and different types of anemia and their therapeutic effects were evaluated. RESULTS: Anemia was observed in 13/33(39%) newly diagnosed CD patients, most of them was mild and normocytic. Incidence of anemia in multicentric CD (MCD) was higher than that in unicentric CD (UCD) (85% vs 10%, P<0.001). Most of CD patients with anemia presented systematic manifestations; moreover, they had higher levels of erythrocyte sedimentation and inflammatory indices, higher incidence of polyclonal hyperimmunoglobulinemia, and higher positive rate of autoantibodies than those without anemia (P<0.05). Except for 2 cases of autoimmune hemolytic anemia (AIHA) and 1 case of anemia secondary to hypersplenism, the anemia in the other 10 patients exhibited features similar to anemia of chronic disease (ACD), whose hemoglobin levels were negatively correlated with the serum levels of C reactive protein and fibrinogen (r -0.917 and -0.717, respectively, P<0.001). Anemia in UCD was cured by the removal of tumor. Yet, anemia in MCD was improved after systemic treatment with immunotherapy and/or chemotherapy. CONCLUSIONS: anemia with an inflammatory and immunologic mechanism presents as a common symptom in MCD, but also can be observed in UCD. In addition to occasional AIHA, anemia associated with CD mainly presents characteristics of ACD. Treatment for anemia in CD is mainly based on the control of primary disease.

Thymic hyperplasia following chemotherapy in adults with lymphoma: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography findings and correlation with T cell repopulation.

Thymic hyperplasia (TH) after chemotherapy is an infrequent phenomenon in adults. This study analyzed the incidence and metabolic activity of TH on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in this population. By reviewing 471 PET/CT recordings of 211 adults with lymphoma, increased FDG uptake within an enlarged thymus regarded as TH was observed in 27 patients aged 18-53 years. FDG uptake in hyperplastic thymus was mild and diffuse, with a maximum standard uptake value (SUVmax) of 2.6±0.9. Its intensity varied with different occurrence times following chemotherapy. In addition, by comparing the recovery of T cell subsets in patients with TH (n=20) and without TH (n=28), no impact of the presence of TH was found on the repopulation of total CD4+and CD8+T cells within the first year after treatment. These data may be helpful to avoid misinterpretation of increased thymic uptake in adults.

[Clinical study of imatinib for treatment of Philadelphia chromosome positive acute lymphoblastic leukemia.].

OBJECTIVE: To explore the efficacy and therapeutic outcome of imatinib combined with chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). METHODS: Thirty patients from Jan 2006 to Mar 2009 were enrolled in this study. All patients received CDOLP induction chemotherapy regimen. Sixteen patients insensitive to chemotherapy were given imatinib simultaneously. Eleven of 30 patients underwent HSCT. The other 19 cases received consolidation therapy including HD-Ara-C, HD-MTX and HD-CTX. Maintenance therapy regimens were VP combined with imatinib. RESULTS: The white blood cell (WBC) count in 17 patients was higher than 30 x 10(9)/L. Of 30 patients, 29 were B cell phenotype and 1 T cell phenotype, 24 had additional chromosomal abnormalities. The overall complete remission (CR) rate was 96.7%. The median CR duration was 9 (2 - 20) months. The 1-year and 3-year overall survival (OS) rates were (64.7 +/- 9.8)% and (30.0 +/- 12.4)%, and the event free survival (EFS) rates were (28.8 +/- 9.5)% and (19.2 +/- 10.1)%, respectively. The bcr-abl transcripts in 13 of 30 patients were continuous negative. The OS rate in patients with negative bcr-abl transcripts was higher than that with positive bcr-abl (70.7% vs 61.3%) (P = 0.189). The EFS rate of patients with continuous negative bcr-abl transcripts was significantly higher than that of patients with continuous positive bcr-abl transcripts (P = 0.01). The median overall survival duration of higher WBC count group and normal WBC count group were 10 (4 - 18) and 29(5 - 36) months, respectively. The patients of higher WBC count had lower OS and EFS rates than that of normal WBC count (46.9% and 15.5% vs 83.5% and 50.8%, respectively) (P = 0.003 and 0.009, respectively). CONCLUSION: Imatinib can significantly improve molecular CR rate and CR duration for Ph(+) ALL patients. Imatinib combined with allo-HSCT is expectable to improve the curative ratio of these patients.