ATG-Fresenius S combined with cyclosporine a: an effective immunosuppressive therapy for children with aplastic anemia.

For the first time, we conducted a 2-center retrospective study to show the efficacy of antithymocyte globulin (ATG)-Fresenius S plus cyclosporine treatment of children with severe aplastic anemia. From March 1997 to May 2011, a total of 124 patients (median age, 7.5 y; range, 1.5 to 16 y) from 2 centers with acquired AA treated with an immunosuppressive therapy (IST) regimen, consisting of ATG-Fresenius S (5 mg/kg per day for 5 d) and cyclosporine, were enrolled. The response rate was 55.6%. The median time between IST and response was 6 (0.5 to 18) months. After a median follow-up time of 29 (6 to 153) months, the rates of relapse and clonal evolution were 3.2% and 0.8%, respectively. Overall, 17 patients (13.7%) died in this study: 14 resulted from sepsis, 1 resulted from intracranial hemorrhage, 1 occurred after hematopoietic stem cell transplantation, and 1 resulted from clonal disease progression. The 5-year overall survival rate for the entire cohort was 74.7%. IST responders had a better survival rate (100%) than nonresponders (70.7%). The use of ATG-Fresenius S plus cyclosporine as a first-line immunosuppressive treatment appeared to be effective for children with severe aplastic anemia in our study. ATG-Fresenius S could be another option in the treatment arsenal, especially in countries where the other ATG products are harder to acquire.

Clinical outcome of childhood lymphoblastic lymphoma in Shanghai China 2001-2010.

BACKGROUND: This retrospective cohort study analysed the clinical characteristics and outcomes of patients with childhood lymphoblastic lymphoma (LBL) treated in Shanghai, China. PROCEDURE: From 2001 to 2010, 108 evaluable patients ≤16 years of age who were newly diagnosed with biopsy-proven LBL were treated with one of three treatment protocols: CCCG-99, SCMC-T-NHL-2002, or LBL-CHOF-2006. RESULTS: Two patients had Stage I disease, 5 had Stage II, 55 had Stage III, and 46 had Stage IV. The immunophenotype was T-cell LBL in 92 patients (85.2%) and precursor B-cell LBL in 16 (14.8%). The abandonment rate was 11.5%. Twenty-five patients (23.2%) suffered from resistant disease, including 1 with isolated central nervous system (CNS) relapse. At a median follow-up of 40.4 months (range, 0-114 months), the 5-year probability of event-free survival (pEFS) was 63.9 ± 4.6% in all patients. The 5-year pEFS for patients with pB-LBL was better than for patients with T-LBL (100% vs. 61.3 ± 5.1%, P = 0.007). Patients who had achieved complete remission on day 33 of induction had significantly better pEFS than those who had not (78.8 ± 4.6% vs. 28.2 ± 9.0%, P = 0.000). Three of 25 patients who experienced resistant disease were alive at the end of the study period. CONCLUSIONS: The abandonment rate was lower for patients with LBL than for patients with acute lymphoblastic leukemia. Prophylactic cranial radiation can be omitted for patients with LBL even when advanced-stage disease is present, as intensive systemic chemotherapy with intrathecal therapy is sufficient to prevent CNS relapse. The survival of patients with resistant disease was very poor.

Risk-adapted chemotherapy without procarbazine in treatment of children with Hodgkin lymphoma.

BACKGROUND: Because procarbazine is not available in the mainland of China, a risk-adapted chemotherapy without the drug was adopted for children with Hodgkin lymphoma (HL) in two tertiary referral centers for childhood cancer in Shanghai. The objective of the present study was to obtain the results comparable with those of previous studies. METHODS: From January 1998 to December 2009, patients below 18 years with newly diagnosed, untreated HL were enrolled in the study. The patients were stratified into risk groups R1 (early stage), R2 (intermediate stage) and R3 (advanced stage). All the patients who had attained a complete remission were not given involved field radiotherapy. RESULTS: Fifty-six patients were eligible for the study. The 4-year event-free survival (EFS) rate was 100%, 80.3%±7.2%, and 62.5%±12.1% for the risk groups R1, R2, and R3, respectively. There was statistically significant difference in EFS between patients with and those without B symptoms (P<0.001). In group R2, the EFS rate was higher for patients treated with chemotherapy combined with radiation (100% vs. 75%±8.8%). But no statistical difference was observed (P=0.177). At the time of evaluation (December 31, 2010), secondary malignancy was not observed. CONCLUSIONS: A significant fraction of children with early stage or intermediate stage HL can be cured with a chemotherapy regimen without procarbazine. Complete response to chemotherapy seems not to be a determinant to omit radiotherapy.

Improved outcome for children with non-high risk acute lymphoblastic leukaemia after using an ALL IC-BFM 2002-based protocol in Shanghai, China.

We report the outcome of 92 non-high risk children with acute lymphoblastic leukaemia (ALL) following a Berlin-Frankfürt-Münster (BFM) Intercontinental ALL -based protocol. Compared with a matched historical control group, we found a lower incidence of treatment-related early death (1·2% vs. 10·9%, P = 0·015), a higher 6-year event-free survival (75·4 ± 4·9% vs. 58·2 ± 6·7%, P = 0·02), reduced total in-hospital costs per person (US $) (10267·0 vs. 18331·0, P < 0·001) and fewer total in-hospital days (164 vs. 296, P < 0·001). This ALL-BFM based protocol was quite tolerable in our institution and will be extended to high-risk patients.

[Comparison of the efficacy of CCCG-97 and BFM-90 protocols in the treatment for children with mature B-cell non-Hodgkin's lymphoma].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Trend in the incidence and geographic variations of acute lymphoblastic leukemia in Shanghai, China from 2002 to 2006.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Compared with the previous data, the incidence of ALL is increased in Shanghai, and has a geographic distribution characteristic.

Developmental definition of MSCs: new insights into pending questions.

Mesenchymal stem cells (MSCs) are a rare heterogeneous population of multipotent cells that can be isolated from many different adult and fetal tissues. They exhibit the capacity to give rise to cells of multiple lineages and are defined by their phenotype and functional properties, such as spindle-shaped morphology, adherence to plastic, immune response modulation capacity, and multilineage differentiation potential. Accordingly, MSCs have a wide range of promising applications in the treatment of autoimmune diseases, tissue repair, and regeneration. Recent studies have shed some light on the exact identity and native distribution of MSCs, whereas controversial results are still being reported, indicating the need for further review on their definition and origin. In this article, we summarize the important progress and describe some of our own relevant work on the developmental definition of MSCs.

[Clinical characteristics of hepatic veno-occlusive disease in 6 children with hematologic neoplasm treated with 6-thioguanine].

OBJECTIVE: 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. METHOD: 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. RESULT: 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. CONCLUSION: HVOD was a serious complication of chemotherapy with 6-TG. Hepatoprotective and jaundice-relieving and low molecular weight heparin could improve the prognosis.

[An epidemiological survey of acute lymphocytic leukemia from 2002 to 2006 in Shanghai.].

OBJECTIVE: To analyse the epidemiological data of acute lymphoblastic leukemia (ALL) in Shanghai. METHODS: ALL cases in Shanghai from 2002 to 2006 were retrospectively investigated. RESULTS: 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) 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. CONCLUSIONS: 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.

Prevalence of ETV6-RUNX1 fusion gene in children with acute lymphoblastic leukemia in China.

A series of 92 Chinese children newly diagnosed with acute lymphoblastic leukemia (ALL) were examined for the ETV6-RUNX1 (previously TEL-AML1) fusion gene by using a nested reverse transcriptase-polymerase chain reaction. ETV6-RUNX1 fusion transcripts were detected in 21 of 92 patients (22.8%): 16 with common ALL, 4 with precursor B-cell ALL, and 1 with T-ALL. The prevalence of ETV6-RUNX1 positivity was 24.7% (20/81) in childhood B-lineage ALL. The prevalence of ETV6-RUNX1 in Chinese pediatric ALL patients proved to be similar to that found in other countries.

Treating childhood acute lymphoblastic leukemia in a developing country 1998-2003: the experience of a single children's hospital in China.

PURPOSE: To assess the outcome of children with acute lymphoblastic leukemia (ALL) treating with ALL China-98 in a single children's Hospital in China. PATIENTS AND METHODS: Between 1998 and June 2003, a total of 58 children in our hospital were treated according to ALL China-98. The patients were >or=1 and

[Association of genetic polymorphism of XRCC1 with susceptibility to acute childhood leukemia].

OBJECTIVE: To explore the association between genetic polymorphisms of XRCC1 and susceptibility to acute childhood leukemia. METHODS: A case-control study with 63 childhood leukemia patients and 66 control subjects was conducted to investigate the role of three XRCC1 polymorphisms (c. 194, c. 280 and c. 399 ) on susceptibility to childhood leukemia. Genotyping was performed using Polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) to detect the single nucleotide polymorphisms (SNPs) of XRCC1 gene. RESULTS: There was a 2.235-fold increased risk of childhood leukemia for individuals carrying XRCC1c. 399 Gin allele (95% CI 1.038 - 4.812) compared with subjects carrying Arg/Arg allele, and the OR among boys was 3.110 (95% CI 1.235 - 7.831). No interaction was found between X-ray exposure and XRCC1 polymorphisms using Logistic regression analysis. CONCLUSION: Polymorphism of XRCC1 gene may contribute to the higher risk of childhood leukemia.

[Polymorphism analysis of 5' promotor region of BCR gene].

BACKGROUND & OBJECTIVE: BCR-ABL fusion gene is regarded as the molecular hallmark of chronic myelogenous leukemia (CML), and its expression is controlled by the BCR gene promoter. This study was designed to investigate the polymorphism of the promoter region of BCR gene, and its possible correlation with the disease. METHODS: A 1.13 kb fragment of BCR gene 5' promotor region was amplified and sequenced from 30 CML patients and 19 controls. Transcription factor binding sites and repeat sequences in this region were analyzed using softwares and online tools. RESULTS: Four novel single nucleotide polymorphisms (SNPs) and 3 bases different from the reference sequence were detected in the region studied. Among these 2 novel SNPs and 1 different base were located in or near several bases of binding sites. The gene frequencies of the novel SNPs had no significant difference between CML and control people. CONCLUSION: Sequence polymorphisms were found in the 5' promotor region of BCR gene, most of them being SNPs. No relativity can be validated between the SNPs and the disease. But it appears that some SNPs might have the probability of bringing influence to the transcription and expression of the gene.

[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].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: EPO levels increased incompensatively in ACD children, which may be a cause of ACD. TNF alpha may cause anemia by inhibiting EPO production.

[Association of HLA-DPB1 alleles with chronic myelogenous leukemia in southern Chinese Hans].

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.