Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis / 中华病理学杂志

To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children's Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (0.759, 0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (0.011, 0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (0.006, 0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% . 94.7%, (2)=4.123, 0.042) and PFS (5-year estimate, 66.7% . 94.7%, (2)=5.822, 0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group ((2)=4.881, 0.027); however, there was no statistical significance in 5-year PFS rate (0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% . 95.7%, (2)=6.285, 0.012; PFS: 65.5% . 91.3%, (2)=5.405, 0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

Comparison of the efficacy of CCCG-97 and BFM-90 protocols in the treatment for children with mature B-cell non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the efficacy and toxicity of the CCCG-97 and BFM-90 protocols in the treatment of pediatric patients with B-cell non-Hodgkin's lymphoma (B-NHL) retrospectively, and to explore the optimal therapeutic strategy.</p><p><b>METHODS</b>Forty-five consecutive untreated patients (age of 18 years or less) with newly diagnosed B-NHL (including Burkitt Lymphoma and diffuse large B-cell lymphoma), treated in our hospital between July 1999 and December 2008 were enrolled in this study. The patients were classified into 2 groups by different protocols. From July 1999 to December 2004, twenty-one 3- to 13.8-year-old children were enrolled in the CCCG-97 group, with 1 in stage I/II, and 20 in stage III/IV(St Jude staging). From January 2005 to December 2008, twenty-four 2.8- to 14.1-year-old cases were enrolled in the BFM-90 group, with 3 in stage I/II, and 21 in stage III/IV (St Jude staging). The survival rates were evaluated by Kaplan-Meier analysis.</p><p><b>RESULTS</b>Forty of the 45 patients (88.9%) reached complete response (CR) after 2 courses of chemotherapy. In the CCCG-97 group, the CR rate was 95.2% (20/21 pts), while that in the BFM-90 group was 83.3% (20/24 pts). At a median follow-up time of 62 (17 to 131) months, the 5-year event-free survival (EFS) was 71.8% for all patients, and 69.1% for Stage III/IV, respectively. In the CCCG-97 group, the 3-year EFS was 76.2%. In the BFM-90 group, it was 75.0%. There was no significant difference in survival rates between the CCCG-97 and BFM-90 groups (P=0.975). Unfavorable events recorded were as follows: Death of progression before achieving CR during induction therapy in 4 cases, and relapse after achieving CR in 6 cases. The relapse rates were 19.0% (4/21 pts) in the CCCG-97 group and 8.3% (2/24 pts) in the BFM-90 group, with a non-significant statistical difference (P=0.292). Major toxicities were myelosuppression and mucositis, especially in the BFM-90 group, but were tolerable and manageable. five patients in the BFM-90 group received rituximab, 2 patients (Stage III) achieved CR, while the other 3 patients (Stage IV) had progressive disease or relapse.</p><p><b>CONCLUSIONS</b>Short-pulse and intensive chemotherapy, stratified according to stage of disease, can improve the survival rate of pediatric mature B-NHL. The efficacy of the CCCG-97 protocol and BFM-90 protocol is comparable and the toxicity is tolerable.</p>

Trend in the incidence and geographic variations of acute lymphoblastic leukemia in Shanghai, China from 2002 to 2006 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Great advances have been made in the diagnosis, molecular pathogenesis and treatment of acute lymphoblastic leukemia (ALL) in the past decade. Due to the lack of large population-based studies, the recent trends in the incidence and geographic variations of ALL in Shanghai, China have not been well documented. To better understand the incidence and epidemiological features of ALL in Shanghai, we conducted a retrospective survey based on the database from the Shanghai Center for Disease Control and Prevention (CDC) and the medical records in all large-scale hospitals in Shanghai, especially those 30 major hospitals with hematology department.</p><p><b>METHODS</b>According to the data from Shanghai CDC, 544 patients, with a median age of 32 years (ranging 1.2 - 89 years), were diagnosed as de novo ALL from January 1, 2002 to December 31, 2006, and they were followed up until December 31, 2007.</p><p><b>RESULTS</b>The average annual incidence of ALL in Shanghai was 0.81/100 000. The incidence in men (0.86/100 000) was slightly higher than that in women (0.75/100 000). The age-stratified incidence showed that the incidence was 2.31/100 000 in patients ≥ 17 years old, 0.54/100 000 in those 18 - 34 years old, 0.46/100 000 in those 35 - 59 years old, and 0.94/100 000 in those ≥ 60 years old. Moreover, there were substantial geographic variations in the incidence of ALL, with the incidence in Chongming county, an island in the east of Shanghai city being 0.60/100 000, much lower than those of other districts. Both French-American-British (FAB) and World Health Organization (WHO) classification systems were applied in the present study. Eighty-eight patients were diagnosed as L1 (26.2%), 193 L2 (57.4%), and 55 L3 (16.4%). For 302 patients with immunophenotypic results, 242 were identified as B cell origin (80.1%), 59 as T cell origin (19.5%), and 1 as biphenotype (0.4%). The leukemia cells in 61 patients co-expressed one or two myeloid antigen (20.2%). For 269 patients with cytogenetic results, the incidences of t(9;22) in patients aged < 10, 11 - 17, 18 - 44, 45 - 59 and ≥ 60 years old were 4.2%, 11.4%, 19.2%, 23.1% and 5.3%, respectively.</p><p><b>CONCLUSION</b>Compared with the previous data, the incidence of ALL is increased in Shanghai, and has a geographic distribution characteristic.</p>

Clinical characteristics of hepatic veno-occlusive disease in 6 children with hematologic neoplasm treated with 6-thioguanine / 中华儿科杂志

<p><b>OBJECTIVE</b>To improve the treatment of drug related childhood hepatic veno-occlusive disease (HVOD), clinical characteristics of 6 children with hematologic neoplasm from 2 hospitals of China Children's Leukemia Group (CCLG) treated with 6-thioguanine (6-TG) complicated with HVOD were analyzed.</p><p><b>METHOD</b>All the drug related HVOD patients were treated with CCLG acute lymphoblastic leukemia (ALL)-2008 protocol. They were from Children's Hospital of Fudan University and Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from April 2008 to April 2009. The diagnosis was made according to the modified Seattle criteria and Baltimore criteria, including 2 or 3 of the following clinical features: hepatomegaly and upper right abdominal pain, jaundice (bilirubin ≥ 35 µmol/L), ascites or confirmed by pathology. The 6 HVOD patients' clinical manifestations, laboratory finding, imageologic and pathologic data were collected and analyzed.</p><p><b>RESULT</b>Of the 6 patients, 2 were males and 4 females. Mean age of the 6 patients was 3.89 years (range from 3 years 1 month to 4 years 11 months). The original disease was acute lymphoblastic leukemia. HVOD occurred during chemotherapy protocols of CAM (CTX + Ara-C + 6-TG) or maintenance period (MTX + 6-TG). Most of 6 HVOD patients presented with pain in liver area, hepatomegaly on imaging, elevated aminotransferase and bilirubin (often ≥ 35 µmol/L), hydroperitonia was common, one with pleural fluid, illegible hepatic veins. All the patients recovered after being treated with hepatoprotective, jaundice-relieving and supportive therapeutics, some patients were treated with low molecular weight heparin. The prognoses were good.</p><p><b>CONCLUSION</b>HVOD was a serious complication of chemotherapy with 6-TG. Hepatoprotective and jaundice-relieving and low molecular weight heparin could improve the prognosis.</p>

An epidemiological survey of acute lymphocytic leukemia from 2002 to 2006 in Shanghai / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the epidemiological data of acute lymphoblastic leukemia (ALL) in Shanghai.</p><p><b>METHODS</b>ALL cases in Shanghai from 2002 to 2006 were retrospectively investigated.</p><p><b>RESULTS</b>All together there were 544 newly diagnozed ALL cases. The yearly incidence of ALL was 0.81/10(5), which was slightly higher in men (0.86/10(5)) than in women (0.75/10(5)). The age-stratified incidence showed 2.31/10(5) in patients (pts) </= 17y, 0.54/10(5) in 18 - 34 y, 0.46/10(5) in 35 - 59 y, and 0.94/10(5) in pts > 60 y. The incidences in Chongming County was 0.60/10(5), being the lowest in all districts. The morphological types of ALL was L(1) (26.2%), L(2) (57.4%) and L(3) (16.4%); the immunophenotype was B (80.1%) and T (19.5%). The incidence of ALL with myeloid antigen expression was 20.2%. Genetic examination revealed that chromosome aberration of t(9;22) was the most common one.</p><p><b>CONCLUSIONS</b>The incidence of ALL in Shanghai is 0.81/10(5). Compared with the national standard (1986 - 1998), the incidence in adolescents is obviously increased. Chongming County has the lowest incidence, indicating a role of environment factor in ALL incidence.</p>

Relationship between tumor necrosis factor alpha, interleukin-6 and erythropoietin in children's with chronic anemia and influence of recombinant human tumor necrosis factor alpha on erythropoietin gene expression / 中华儿科杂志

<p><b>OBJECTIVE</b>The anemia of chronic disease (ACD) is usually defined as mild to moderate anemia occurring during the chronic infection, inflammation, neoplasm or trauma. It is the most common anemia among in-hospital adults. The insufficient endogenous erythropoietin (EPO) production is probably one of the pathogenic mechanisms of ACD. Inflammatory cytokines play an important role in the ACD pathogenesis. But nowadays there are few published papers on the childhood ACD in the world. This study aimed to detect the EPO levels in children's ACD, to explore the relationship between EPO and tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) and, to evaluate the effect of recombinant human TNF alpha (rhTNF-alpha) on EPO gene expression.</p><p><b>METHODS</b>Sixty children were divided into ACD group (20 children), non-anemia (NA) group (19 children) and iron deficiency anemia (IDA) group (21 children) according to clinical diagnosis. Serum TNF alpha and IL-6 levels were detected with ELISA method. The EPO level was detected by chemical immulite method. The effect of rhTNF alpha on the expression of EPO gene was studied by culturing Hep G2 cell line and RT-PCR method.</p><p><b>RESULTS</b>Serum EPO levels were different among the 3 groups (F = 44.68, P < 0.01). Serum EPO levels in ACD group were higher than those in NA group, while the hemoglobin levels were similar between the two groups. Serum EPO levels in ACD patients were lower than those in IDA patients. Serum TNF alpha levels were different among the 3 groups (F = 25.15, P < 0.01), and serum IL-6 levels were also different among the 3 groups (F = 13.16, P < 0.01). Serum TNF alpha and IL-6 levels in ACD group were higher than those in NA group. In ACD group, serum levels of both TNF alpha and IL-6 were not correlated to the serum level of EPO (r = -0.35, P > 0.05 and r = -0.05, P > 0.05, respectively). In vitro, rhTNF alpha inhibited the expression of EPO mRNA in hypoxia, and the inhibitory effects became stronger with the increase of rhTNF alpha (F = 64.20, P < 0.01).</p><p><b>CONCLUSION</b>EPO levels increased incompensatively in ACD children, which may be a cause of ACD. TNF alpha may cause anemia by inhibiting EPO production.</p>

Association of HLA-DPB1 alleles with chronic myelogenous leukemia in southern Chinese Hans / 中国实验血液学杂志

To clarify the association between HLA-DPB1 alleles and chronic myelogenous leukemia (CML) in South Chinese, the allelic types of HLA-DPB1 were detected by sequence based typing (SBT) in 86 patients with CML and 82 healthy individuals from Southern China. The results showed that the frequencies of HLA-DPB1 * 1301 and DPB1 * 20011 were higher in patients with CML in comparison with those of healthy individuals. It is concluded that positive association may exist between certain HLA-DPB1 alleles and CML.