[Show abstract][Hide abstract] ABSTRACT: Graft failure and survival are major problems for aplastic anemia patients undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti-HLA antibodies negatively impact graft failure in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic-HSCT at a single institution between 2006 and 2012 investigated the influence of anti-HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti-HLA antibodies. Pre-existing anti-HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti-HLA class I antibodies. Anti-HLA antibodies were associated with worse 5-year survival (78.6% vs 100%, p=0.021) and higher treatment-related mortality (21.4% vs 0%, p=0.028) compared with antibody-negative patients. Anti-HLA class I antibody-positive patients had poorer 5-year survival (75.0%) than anti-HLA class I&II antibody-positive and -negative patients (87.5% and 100.0% respectively, p=0.039). Presence of anti-HLA class I antibodies (p=0.024) and older age (10yrs or more) (p=0.027) significantly increased the risk of post-HSCT mortality. Pre-existing anti-HLA antibodies negatively affect the outcome of HSCT in pediatric aplastic anemia patients. Routine testing for anti-HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Pediatric Hematology/Oncology 05/2014; · 0.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (131I) against the human vascular endothelial growth factor (hVEGF).
hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment.
I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control.
EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging.
BMC Cancer 02/2014; 14(1):114. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this work, four kinds of cellulose aliphatate esters, cellulose acetate (CA), cellulose propionate (CP), cellulose butyrate (CB) and cellulose acetate butyrate (CAB) are synthesized by the homogeneous acylation reactions in cellulose/AmimCl solutions. These cellulose aliphatate esters are used to prepare gas separation membranes and the effects of molecular structure, such as substituent type, degree of substitution (DS) and distribution of substituents, on the gas permeability are studied. For CAs, as the DS increases, their gas permeabilities for all five gases (O2, N2, CH4, CO and CO2) increase, and the ideal permselectivity significantly increases first and then slightly decreases. At similar DS value, the homogenously synthesized CA (distribution order of acetate substituent: C6 > C3 > C2) is superior to the heterogeneously synthesized CA (distribution order of acetate substituent: C3 > C2 > C6) in gas separation. With the increase of chain length of aliphatate substituents from acetate to propionate, and to butyrate, the gas permeability of cellulose aliphatate esters gradually increases. The cellulose mixed ester CAB with short acetate groups and relatively long butyrate groups exhibits higher gas permeability or better permselectivity than individual CA or CB via the alteration of the DS of two substituents.
Chinese Journal of Polymer Science 01/2014; 32(1). · 1.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute Myeloid Leukemia (AML), a cancer of the myeloid line of blood cells, progresses rapidly and is typically fatal within weeks or months if left untreated. Asparaginases are a class of enzymatic anti-leukemia agents that induce apoptosis in leukemia cell lines; however, the role of L-asparaginase in the induction of apoptosis in AML cells has not been investigated. In this study, we investigated the apoptosis-inducing effect of L-asparaginase and its underlying mechanism in AML U937 cells. The results showed that L-asparaginase significantly inhibited the proliferation of U937 cells by inducing apoptosis. Furthermore, the low baseline expression level of asparaginase synthase (ASNS) demonstrated the sensitivity of U937 cells and AML M5, a rare subtype of AML, to L-asparaginase. Apoptosis induced by L-asparaginase is mediated by apoptosis-inducing factor (AIF). Our findings show the potential of L-asparaginase as an effective approach in treating AML via the induction of apoptosis mediated by AIF.
Frontiers in Bioscience 01/2014; 19:515-27. · 4.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We retrospectively analysed the outcomes of 127 children with acquired severe aplastic anaemia (SAA) who had received haematopoietic stem cell transplantation (HSCT) between 2000 and 2011 in one of the 10 Asia Pacific institutions. Fifty-three were matched sibling donor (MSD) and 74 were alternative donor (AD), including 22 matched unrelated donor, 32 mismatched unrelated donor and 20 mismatched related donor. With a median follow up 45·5 months (13-139) and when compared to the MSD group, AD recipients had more grade II-IV acute graft-versus-host disease (aGVHD; 14·3% vs. 32·8%, P = 0·029), but similar grade III-IV aGVHD (10·2% vs. 12·5%, P = 0·774), graft failure (GF) (15·1% vs. 15·5%, P = 0·658) and 5-year overall survival (90·6% vs. 83·7%, P = 0·251). As a source of stem cell, peripheral blood stem cells (PBSC) resulted in less GF (18% vs. 9·1% P = 0·013), similar grade II-IV aGVHD (28·1% vs. 17·4%, P = 0·258), chronic GVHD (25·8% vs. 29·3%, P = 0·822) and similar outcomes (89·7% vs. 82·4%, P =0 ·665) when compared to bone marrow (BM). In univariate analysis, GF (P < 0·001) and grade II-IV aGVHD (P = 0·009) were predictors of poor survival. In multivariate analysis, only GF was associated with poor survival (P = 0·012). The outcome of AD and PBSC HSCT were comparable to that of MSD and BM HSCT in the Asia Pacific region.
British Journal of Haematology 06/2013; · 4.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To analyze outcomes and prognostic factors of children with B-cell non-Hodgkin lymphoma (B-NHL). METHODS: One hundred and four newly diagnosed B-NHL children were enrolled in protocol of B-NHL 2001. The statistics were performed by SPSS 13.0. RESULTS: Of 104 children (79 males, the median age of 7.1 years), 60, 32 and 4 patients were diagnosed with Burkitt lymphoma, diffuse large B-cell lymphoma and unclassifiable B-cell lymphoma, respectively. Four patients were in stage Ⅰ, 27 stage Ⅱ, 55 stage Ⅲ and 18 stage Ⅳ; 1, 26 and 77 patients were allocated into R1, R2 and R3 risk groups, respectively. Three patients never got complete remission (CR), 9 patients relapsed after CR with the duration of relapse from 1 to 7 months after chemotherapy. The estimated 5-year EFS of 104 patients was (86.7±3.5)%. Univariable analyses identified that risk factors for recurrence were of higher staging, elevated LDH, serum ferritin and poor early response. Age, sex, pathologic diagnosis, original tumor, bone or marrow involvement, C-MYC and risk group were not found to be associated with the risk of failure to treatment. Multivariable COX regression models confirmed serum ferritin as a significant independent prognostic marker. CONCLUSION: B-NHL 2001 protocol was reasonable for B-NHL children. Higher staging, elevated LDH, serum ferritin and poor early response increased risk for recurrence.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 05/2013; 34(5):399-403.
[Show abstract][Hide abstract] ABSTRACT: Breast cancer is the second leading cause of cancer death in women today. Once breast cancer metastasizes to bone, mortality increases. Thus, there is an urgent need to identify patients with high risk of bone metastasis, and to find predictive factors for the occurrence of bone metastasis at an earlier stage of breast cancer. Three hundred and sixty patients with pathologically proved breast cancer visiting the Department of Nuclear Medicine for whole body bone scan from January 2006 and January 2009 were investigated in this study. Clinicopathological information was obtained, which consisted of age, menopausal status, clinical staging, lymph node stage, histological grade, the expression of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2). Correlation between bone metastasis and the associated factors was tested by using the Chi-square test. A Cox multivariate analysis was used to assess the factors which independently contributed to survival after bone metastasis in breast cancer patients. Survival curves were drawn for metastasis-free interval and the independent factors which contributed to survival, using the Kaplan-Meier method. Twenty-four patients were excluded from subsequent analysis. Three hundred and thirty-six enrolled patients ranged in age from 22 to 77 years (mean, 47.8 years). ER/PR status [ER(+) vs. ER(-), χ (2)=4.328, P=0.037; ER(+)PR(+) vs. ER(+)PR(-), χ (2)=4.425, P=0.035] and histological grade (χ (2)=7.131, P=0.028) were significantly associated with bone metastasis. ER status (x (2)=8.315, P=0.004) and metastasis-free interval (χ (2)=6.863, P=0.009) were independent prognostic factors for survival in breast cancer patients with bone metastasis. Our study suggested that ER/PR status and histological grade are risk factors for the development of bone metastasis in breast cancer patients. However, ER status and metastasis-free interval are independent prognostic factors for survival in breast cancer patients with bone metastasis. Breast cancer bone metastasis has its unique characteristics, which is helpful to choose the appropriate treatment for breast cancer patients with bone metastasis.
Journal of Huazhong University of Science and Technology 02/2013; 33(1):122-5. · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To investigate the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with chronic myelogenous leukemia (CML), and to analyze the possible prognostic factors.Methods
The clinical data of 20 children with CML who had received allo-HSCT was analyzed retrospectively to investigate possible prognostic factors, including age, sex, interval between diagnosis and transplantation, HLA matching between donors and recipients, illness status on transplantation and acute and chronic graft-versus-host disease (GVHD).ResultsAt the end of follow-up, 13 of the 20 treated children had disease-free survival (DFS) and the rest (7 cases) died. Four died of severe acute GVHD, two of chronic GVHD and its complications, and one of relapse after transplantation. The three-year DFS was (64.6±1.1%). As shown by the univariate analysis, age was the most important prognostic factor in children with CML who had received allo-HSCT (P<0.05), and in children over 10 years, the prognosis was poor. No other of the above factors had a significant impact on prognosis (P>0.05). The multivariate logistic regression analysis also confirmed age as the only prognostic factor (P<0.01). Severe acute and/or chronic GVHD was the most important cause of patient death. 10/10 HLA-matched donors could improve the transplantation outcome.Conclusions
Allo-HSCT is an effective treatment for children with CML. To improve the prognosis and treatment outcome, children with CML aged over 10 years should receive allo-HSCT as early as possible. 10/10 HLA-matched donors are preferred in allo-HSCT and GVHD should be prevented.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 01/2013; 15(1):19-24.
[Show abstract][Hide abstract] ABSTRACT: 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.
World Journal of Pediatrics 12/2012; · 1.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute lymphoblastic leukemia includes T-cell acute lymphoblastic leukemia (T-ALL) and B-cell acute lymphoblastic leukemia (B-ALL). In children, T-ALL usually has a worse prognosis than B-ALL, although childhood T-ALL prognoses have improved remarkably. The varying outcomes among T-ALL cases suggest that an unrecognized biological heterogeneity may contribute to chemo-resistance. Deep exploration of T-lymphocyte development in recent years has found a subgroup of patients with a phenotype that resembles early T-cell precursor, which confers a much poorer prognosis than any other form of T-ALL. This novel subtype of T-ALL was called early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Flow cytometry data from T-ALL patients enrolled in Shanghai Children's Medical Center between July 2002 and October 2010 were assessed according to Dr. Campana's protocol. Among total 89 T-ALL cases, 74 cases had enough immunophenotype data available to differentiate between ETP (CD1a(-), CD8(-), CD5(dim), at least one marker of stem cell or myeloid lineage) and non-ETP. From these 74 subjects, 12 ETP-ALL cases (16.2%) were identified. The event-free survival (EFS) rate at 66.8 months was 11.1% ± 10.1% for ETP-ALL and 57.6% ± 5.6% for non-ETP-ALL (P = 0.003). The overall survival rates were 13.3% ± 11.0% for ETP-ALL and 64.7% ± 6.3% for non-ETP-ALL (P = 0.002). Our findings demonstrate that early T-cell precursor leukemia is a very high-risk subtype of acute lymphoblastic leukemia with poor prognosis.
[Show abstract][Hide abstract] ABSTRACT: To explore the incidence, clinical characteristics and prognosis of children and adolescents over 10 years of age with acute lymphoblastic leukemia (ALL).
From May 1, 2005 to April 30, 2009, 67 newly diagnosed ALL children and adolescents over 10 years of age were enrolled in protocol of ALL-2005. All of the clinical characteristics of the patients were analyzed. The statistics was done by SPSS 13.0.
There were 40 males (59.7%) and 27 females (40.3%). The mean age at diagnosis was 12.3 ± 1.7 (10.0 to 17.8) years with median age of 12.2 years. Of 67 patients, 48 were in medium risk group, and 19 in high risk group. During induction therapy, 83.6% and 86.6% patients had good response to prednisone and bone marrow blasts ≤ 5% at day 19, respectively. The overall hematologic response rate in these 67 patients was 88.1% (59) in complete remission (CR) after induction therapy, 15 patients relapsed with mean continuous CR period of (14.9 ± 9.9) months. The five-year event-free survivals (EFS) and overall survivals (OS) were (64.4 ± 6.3)% and (74.1 ± 6.1)%, respectively. According to univariate analysis, elevated serum ferritin, bcr-abl translocation, poor response to prednisone, high bone marrow blasts at day 19 or after induction therapy, and high minimal residual disease (MRD) after induction therapy increased risk for recurrence. Multivariate analysis indicated that high MRD after induction therapy was associated with recurrence (RR = 2.20, 95%CI 1.26 - 3.84, P < 0.01).
Survival has improved for children and adolescents with ALL by ALL-2005 protocol. Analysis of serum ferritin and bcr-abl translocation at diagnosis, early responses to treatment and MRD detection during therapy are powerful prognostic indicators.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 12/2011; 32(12):840-3.
[Show abstract][Hide abstract] ABSTRACT: Superparamagnetic iron oxide (SPIO) nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility. A variety of studies have shown the exciting potential of functionalized SPIO nanoparticles, such as surface-coated, targeted ligandconjugated, and/or drug-loaded SPIO nanoparticles, as powerful tools for targeted imaging and therapy. Moreover, the applications of SPIO nanoparticles that integrate diagnosis and therapy in SPIO nanoparticles facilitate the monitoring of therapeutic efficacy during treatment. In the present review, we primarily concentrate on the recent advancements in the field of SPIO nanoparticles in terms of synthesis, targeted therapy, and cancer imaging.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
Compared with the previous data, the incidence of ALL is increased in Shanghai, and has a geographic distribution characteristic.
Chinese medical journal 08/2011; 124(16):2406-10. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study quantitatively examined signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels in peripheral blood of children with acute lymphoblastic leukemia (ALL) at different stages in order to evaluate the role of sjTRECs in predicting severe infection postchemotherapy.
sjTRECs levels in peripheral blood were measured by fluorescent quantitation-polymerase chain reaction in 30 children with newly diagnosed ALL, 36 children with ALL who accepted chemotherapy but were not infected, 30 children with ALL who had severe infection after chemotherapy, and 50 normal children.
Blood sjTRECs levels in the normal group (394 ± 270 copies/103 MNC) were significantly higher than those in the other three groups (P<0.05). Blood sjTRECs levels in the chemotherapy group without infection (96 ± 78 copies/103 MNC) were significantly lower than those in the newly diagnosed ALL group (210 ± 219 copies/103 MNC) (P<0.05). The chemotherapy group with severe infection showed the lowest blood sjTRECs levels (48 ± 40 copies/103 MNC) in the four groups.
The measurement of blood sjTRECs levels might be helpful for predicting the occurrence of severe infection postchemotherapy in children with ALL.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 06/2011; 13(6):466-70.
[Show abstract][Hide abstract] ABSTRACT: Postoperative chylous leakage is a rare complication that results from disruption of either mediastinal or retroperitoneal lymphatic channels during dissection or from obstruction by original lesions such as a malignancy. There is lack of clinical experience in pediatric patients about how to manage the leakage and what the result will be.
We retrospectively analyzed the clinical outcomes of 5 children with neuroblastoma (NB) (stage 4 in 4 children and stage 1-2 in 1 child) who had received non-surgical treatment of chylothorax and/or chylous ascites after retroperitoneal/posterior mediastinal extensive radical resection of NB for complete tumor removal. Conservative therapy with low-fat diet, medium-chain triglyceride and/or total parenteral nutrition was the mainstay treatment for chylous leakage.
Four of the 5 children recovered after 6-32 days of conservative treatment, and the last one who did not respond was cured by surgical management for chylous fistula 45 days after primary surgery. Postoperative imaging showed that more than 90% of tumors were resected and all of them showed very good partial remission (VGPR). Among the 4 patients in stage 4, 3 relapsed after radical resection of NB. The patient of stage 1-2 was still in VGPR.
The majority of patients with chylous ascites/chylothorax after extensive radical surgery for posterior mediastinum/retroperitoneum NB could be cured by non-surgical treatment. But the final result of original disease has not been greatly changed by intensive surgery for stage 4 NB.
World Journal of Pediatrics 06/2011; 8(2):151-5. · 1.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in the treatment of acute myeloid leukemia (AML). The purpose of this study was to evaluate the efficacy and toxicity of HHT for de novo pediatric AML. Patients entered in this study were treated with a regimen including HHT 3.5 mg/m(2) day for 9 days for 6-8 cycles after induction and consolidation with cytarabine plus daunorubicin (DA). One hundred and seventy-one eligible patients, with a median age of 7.58 years, were enrolled. Complete response was obtained in 140/171 (81.9%) cases within 60 days (2 cycles) after DA induction. The 5-year event-free survival was 52.75%. Severe myelosuppression was seen in all patients, with an average minimum WBC count of 686/μl. Following the HHT-including regimen, one patient suffered severe pancreatitis, and a second with a history of congenital hepatitis B suffered liver failure. No significant drug-induced hypotension, fluid retention, hyperglycemia, or cardiac toxicity was detected in this study. Other toxicities, including nausea, vomiting, diarrhea, and mucositis, were mild. HHT-including protocols may emerge as useful therapeutic options in future clinical trials.
International journal of hematology 05/2011; 93(5):610-7. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This pilot study focused on whether flow cytometry (FCM) detection of minimal residual disease in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma (NB).
Fifty-seven stage 4 NB patients with BM infiltration were enrolled in this study. All of them received NB-2001 protocol. BM samples were examined for tumor cell contamination by both morphology and FCM with CD45-FITC/CD81-PE/CD56-PECy5 monoclonal antibodies cocktail at diagnosis and after 4 courses of chemotherapy.
BM samples of all patients were positive at diagnosis by FCM, and samples from 30 patients became negative after 4 courses of chemotherapy, 10 patients relapsed (33.3%) in mean 45.5 months, range 7 to 69. Another 27 patients remained positive, and 20 of them relapsed (74.1%) in mean 24.2 months, range 8 to 48. There was a statistically significant difference in event-free survival between the 2 groups (P = 0.002).
Persistence of minimal residual disease in BM may work as a chemotherapy response marker and predict the prognosis in advanced NB.
American journal of clinical oncology 04/2011; 35(3):275-8. · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated the intracellular localization of asparagine synthetase (ASNS) in the relation with chemoresistance in leukemia. pIRES-GFP-ASNS-Flag/Neo expression vector was transiently tansfected into SK-N-MC cells and 297T cells respectively. Immunofluorescence and Western blot analysis were performed for cellular localization of ASNS respectively. U937 cells were treated with L-asparaginase for 48 h and examined for endogenous ASNS expression on plasma membrane by immunofluorescence staining. Immunofluorescence staining showed that the transiently expressed ASNS was partly localized on transfected-SK-N-MC cell surface. Moreover, Western blotting exhibited that ASNS expressed both in cytosol and on plasma membrane of transfected-293T cells. Immunofluorescence staining with anti-ASNS-specific monoclonal antibody revealed that endogenous ASNS was localized on the plasma membrane of U937 cells, except for its distribution in the cytosol. In addition, ASNS exhibited a higher expression on plasma membrane after treatment with L-asparaginase as compared with the untreated cells. It was concluded that the subcellular translocation of ASNS may play an important role in L-asparaginase resistance in leukemia cells.
Journal of Huazhong University of Science and Technology 04/2011; 31(2):159-63. · 0.78 Impact Factor