Comparison of outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal GIST: An inverse probability of treatment weighting analysis.

BACKGROUND AND OBJECTIVES: This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients. METHODS: Eighty-five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis. RESULTS: The response rate to neoadjuvant imatinib was 65.9%. After the IPTW-adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence-free survival (DRFS) and disease-specific survival (DSS) compared with those who underwent upfront surgery (5-year DRFS 97.8 vs. 71.9%, hazard ratio [HR], 0.15; 95% CI, 0.03-0.87; p = 0.03; 5-year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01-0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5-year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03-1.15). CONCLUSIONS: In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor-related deaths when compared to upfront surgery and adjuvant imatinib alone.

Effect of Inhibitors on Hydrogen Bond Reduction and Kaolinite Dissolution for Enhanced CO2 Adsorption in Coal.

The application of an inhibitor to the remaining coal in the goaf not only prevents spontaneous combustion of the coal seam in the mining area but also greatly enhances the capacity of coal to adsorb CO2. To investigate the mechanism by which inhibitors improve the CO2 adsorption capacity of the coal seam in the goaf, we conducted swelling experiments, infrared spectroscopy, scanning electron microscopy, and X-ray diffraction analyses to examine the microstructural changes in the adsorption of CO2 before and after inhibition. The results indicate that after inhibition, the number of hydrogen bonds between coal macromolecules decreased, and the samples exhibited approximately 5% swelling. This swelling of the coal macromolecular structure and the increased distance between coal particles create additional space for CO2 sequestration, which is a critical factor contributing to the enhanced CO2 adsorption capacity of coal. The mineral composition of coal consists of 75.6% kaolinite, and inhibition leads to a reduction in kaolinite content by 0.8-7.9%. After inhibition, the swelling and disintegration of kaolinite cause uneven stress, resulting in changes to the pore structure. Closed pores filled with kaolinite transform into open pores, and the original pores crack, forming new pores and pore channels. The dissolution of kaolinite particles increases the porosity of the coal, further facilitating gas adsorption. Among the three inhibitors tested, the most effective in enhancing CO2 sequestration by bituminous coal in the mining area was the urea solution. This study holds significant importance in improving the CO2 sequestration capacity of residual coal in goaves.

Significance of myeloid antigen expression in precursor T lymphoblastic lymphoma.

BACKGROUND AND OBJECTIVE: Precursor T lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma. Myeloid antigen expression was found in some of the patients, and its clinical significance is worth studying. This study was to compare the clinical features, short-term efficacy and survival of T-LBL patients with or without myeloid antigen expression so as to evaluate its prognostic significance. METHODS: Forty-five T-LBL patients, with a median age of 14 years, were treated at Sun Yet-sen University Cancer Center between January 2000 and July 2008. These patients were divided into myeloid antigen-positive group (My(+) group) and myeloid antigen-negative group (My(-) group) based on the flow cytometric (FCM) analysis in bone marrow or pleural fluid. Myeloid antigen expression and its correlation with the short-term efficacy and overall survival were assessed in the two groups. RESULTS: There were 18 patients (40.0%) in the My(+) group and 27 (60.0%) in the My(-) group. The myeloid antigen expression was negatively correlated with the initial level of lactate dehydrogenase (LDH), but not with other clinical features. The remission rate was lower in the My(+) group than in the My(-) group (38.8% vs. 70.3%, P = 0.028). The 2-year overall survival rate was lower in the My(+) group than in the My(-) group (51.9% vs. 78.7%, P = 0.036). By age subgroup analysis, there were no differences in response and survival rate among children and adolescents with or without myeloid antigen expression. But the remission rate and the 2-year overall survival rate were significantly lower in adult patients with myeloid antigen expression than in patients without it. Univariate and multivariate analysis demonstrated that age and myeloid antigen expression were adverse prognostic factors. CONCLUSION: Myeloid antigen expression is a predictor of a poor response to chemotherapy, and adverse prognostic factor in adult T-LBL, but not in children with T-LBL.

Nomogram for predicting pathological complete response and tumor downstaging in patients with locally advanced rectal cancer on the basis of a randomized clinical trial.

BACKGROUND: Preoperative fluoropyrimidine with radiotherapy was regarded as the standard of care for locally advanced rectal cancer (LARC). The model for predicting pCR in LARC patients was based on standard treatment only. This study aimed to establish a nomogram with pretherapeutic parameters and different neoadjuvant regimens for predicting pathologic complete response (pCR) and tumor downstaging or good response (ypT0-2N0M0) after receiving neoadjuvant treatment in patients with LARC based on a randomized clinical trial. METHODS: Between January 2011 and February 2015, 309 patients with rectal cancer were enrolled from a prospective randomized study (NCT01211210). All pretreatment clinical parameters were collected to build a nomogram for predicting pCR and tumor downstaging. The model was subjected to bootstrap internal validation. The predictive performance of the model was assessed with concordance index (C-index) and calibration plots. RESULTS: Of the 309 patients, 53 (17.2%) achieved pCR and 132 (42.7%) patients were classified as tumor downstaging with ypT0-2N0M0. Based on the logistic-regression analysis and clinical consideration, tumor length (P = 0.005), tumor circumferential extent (P = 0.036), distance from the anal verge (P = 0.019), and neoadjuvant treatment regimen (P < 0.001) showed independent association with pCR following neoadjuvant treatment. The tumor length (P = 0.015), tumor circumferential extent (P = 0.001), distance from the anal verge (P = 0.032), clinical T category (P = 0.012), and neoadjuvant treatment regimen (P = 0.001) were significantly associated with good tumor downstaging (ypT0-2N0M0). Nomograms were developed to predict the probability of pCR and tumor downstaging with a C-index of 0.802 (95% confidential interval [CI], 0.736-0.867) and 0.730 (95% CI, 0.672-0.784). Internal validation revealed good performance of the calibration plots. CONCLUSIONS: The nomogram provided individual prediction responses to different preoperative treatment for patients with rectal cancer. This model might help physicians in selecting an optimized treatment, but warrants further external validation.

[Modified BFM-90 regimen greatly improves treatment outcomes of chinese childhood and adolescent lymphoblastic lymphoma].

OBJECTIVE: This study was designed to evaluate the efficacy and toxicity of modified BFM-90 regimen originated from Germany authors in the treatment of Chinese childhood and adolescent lymphoblastic lymphoma. METHODS: Thirty-six untreated lymphoblastic lymphoma patients aged from 3 to 18 years were included, with 1 patient in stage II , 9 in stage III and 26 in stage IV. Of these 36 patients, 28 (77.7%) were diagnosed as T cell phenotype, 26 (72. 2%) were found to have mediastinal mass, 21 (58. 3%) had bone marrow involvement. All patients received chemotherapy of modified BFM-90 regimen consisting of induction remission, central nerve system prophylaxis, re-induction remission and maintenance therapy. Total treatment duration was two years. The difference from standard BFM-90 is that we omitted cranial radiotherapy but gave regular high dose methotrexate (MTX) iv infusion and intrathecal MTX therapy during maintenance therapy period. Kaplan-Meier method was used to evaluate survival rate. RESULTS: Of 36 patients, 32 (88%) achieved complete remission (CR) , 1 (2. 7%) partial remission (PR) with an overall response rate of 90.7%. One patient had disease progression ( DP). Two patients received autologous stem cell transplantation at CR1, and two patients received radiotherapy to mediastinum. Totally, 5 patients relapsed, while 2 of them were still alive after salvage chemotherapy. The other 3 died of tumor progression. Two patients died during induction remission, 1 of fungal septicemia, the other of cerebral hemorrhage; one PR and one DP patient died of disease, therefore, totally 7 patients died at last. Median follow-up time was 28 months. Overall three-year survival rate was 78. 3%. The major toxicity was myelosuppression. CONCLUSION: Modified BFM-90 protocol can improve the efficacy and survival of Chinese childhood and adolescent lymphoblastic lymphoma with tolerable toxicity. However, this modified protocol should only be used in experienced cancer center or hematological unit.

Impact of HLA-E gene polymorphism on HLA-E expression in tumor cells and prognosis in patients with stage III colorectal cancer.

Human leukocyte antigen (HLA)-E can contribute to the escape of cancer cells from host immune mechanisms. However, it is unknown whether HLA-E gene polymorphisms might play a role in cancer immune escape. This study aimed to evaluate the correlation between HLA-E gene polymorphisms and HLA-E expression in tumor tissue and determine the effects on clinical outcome of patients with stage III colorectal cancer. Two hundred thirty patients with stage III colorectal cancer were enrolled. HLA-E expression was detected in patient-derived tumor tissues with immunohistochemistry. HLA-E gene alleles in tumor tissues were detected with the polymerase chain reaction-sequence-specific primer method. In colorectal cancer tissue and in the normal tissue adjacent to the tumor, the HLA-E expression rates were 72.2 and 15.1 %, respectively (P < 0.05). Patients with overexpression, low expression, and no expression of HLA-E exhibited disease-free survival of 55.3, 72.9, and 72.1 %, respectively. Patients with HLA-E overexpression exhibited the lowest long-term survival rate. No relationship was observed between the type of HLA-E gene polymorphism and its expression level in tumor tissues; moreover, no polymorphisms appeared to affect the long-term survival of patients with colorectal cancer. The type of HLA-E polymorphism did not have an impact on HLA-E expression in tumors or the prognosis in patients with stage III colorectal cancer. However, the level of HLA-E expression in tumor tissue strongly predicted long-term survival in these patients.

[Prophylaxis and treatment of modified BFM-90 regimen for lymphoblastic lymphoma in children and adolescents accompanied with infection].

BACKGROUND AND OBJECTIVE: Modified BFM-90 regimen has significantly improved the outcome of lymphoblastic lymphoma in children and adolescents. Infection is the main side effect of this regimen, which may affect the treatment efficacy and prognosis without proper intervention. This study was to summarize the characteristics of the modified BFM-90 regimen related infection, and explore effective approaches to treat the infection. METHODS: The infection rate, site, pathogen were reviewed for the infections of 104 children and adolescents suffering from lymphoblastic lymphoma at different phases of the modified BFM-90 regimen. The relationship between chemotherapy, bone marrow suppression and infection was analyzed. The value of procalcitonin (PCT) in identifying the infection type and the outcome of anti-infection treatment was evaluated. RESULTS: The infection rates in reduction phases Ia, Ib and re-reduction phases IIa, IIb were 52.5%, 60.7% and 48.6%, 28.2%, respectively. The infection rate in consolidation chemotherapy for patients with low to intermediate risk and high risk were 17.2% and 100%, respectively. In total 302 infections occurred. One hundred and sixty-seven cases (55.3%) had documented infection sites, most of which happened to the respiratory tract. Ninety-five cases (31.5%) had documented pathogens, most of which were Gram-negative bacteria. Infections of 262 cases (86.8%) were secondary to bone marrow suppression. The sensitivity and specificity of PCT in diagnosing sepsis were 83.3% and 70.2%, but it failed to identify the infection type. After the anti-infection treatment, 296 cases were cured, four cases gave up further treatment due to financial difficulties, two cases died of sepsis. CONCLUSIONS: Infections caused by modified BFM-90 regimen for lymphoblastic lymphoma in children and adolescents are closely correlated to bone marrow suppression. The positive diagnosis rate of the pathogen is too low to identify most of the infection type. The treatment still mainly depends on experience.

[Correlation between peripheral blood CD4+CD25high CD127low regulatory T cell and clinical characteristics of patients with non-Hodgkin's lymphoma].

BACKGROUND AND OBJECTIVE: Non-Hodgkin's lymphoma (NHL) is a malignant disease originating from immune system. Studies of the possible relationship between NHL and immune suppression status are of great concern. Regulatory T cell (Treg) is a subtype of T cells that exert an immunosuppressive function. However, the relationship between Treg and lymphoma is controversial. The study was to detect peripheral blood levels of Treg in patients with NHL and healthy adults, and to explore the possible relationship between peripheral blood Treg level and NHL. METHODS: By using flow cytometry with surface staining fluorochrome-conjugated antibodies for CD4, CD25, CD127, the percentages of CD4+CD25highCD127low Treg in peripheral blood of 31 healthy adults and 99 newly diagnosed NHL patients, hospitalized in Sun Yet-sen University Cancer Center from December 2006 to March 2008, were detected and analyzed. RESULTS: The average peripheral blood CD4+CD25highCD127low Treg levels were 8.07+/-1.90 and 11.20+/-4.40 in healthy adults and newly diagnosed NHL patients, respectively. The difference of peripheral blood Treg levels between them was statistically significant (P<0.001,95% CI:2.02-4.23). The peripheral blood level of Treg was significantly higher in the male NHL patients than in the female patients (P=0.030,95% CI:0.19-3.77). Patients with bad habits (smoking, addict to drink, or both) had significantly higher peripheral blood Treg level than patients without bad habits (P=0.045,95%CI:0.04-3.84). It was no significant relation between peripheral blood Treg level and age, stage, IPI, B symptom, bulky disease, LDH level, pathologic subtype, short term response, HBV infection, and so on. The analysis in diffuse large B-cell lymphoma (DLBCL) subtype showed the same results. CONCLUSIONS: Newly diagnosed NHL patients are in an immunosuppressive statue. Patients with bad habits (smoking, addict to drink, or both) have higher peripheral blood Treg level. Peripheral blood Treg level is irrelevant to the status of disease.

[Efficacy and survival of 92 cases of Ewing's sarcoma family of tumor initially treated with multidisciplinary therapy].

BACKGROUND AND OBJECTIVE: Ewing's sarcoma family of tumor (ESFT) is aggressive. The optimal therapy modality for ESFT is still to be found. This study was to explore the clinical characteristics and therapy for ESFT. METHODS: Ninety-two cases of ESFT were collected from January 1995 to April 2008 in Sun Yat-sen University Cancer Center and analyzed retrospectively. RESULT: Of 92 cases, 23 were Ewing's sarcoma of bone, 21 extraosseous Ewing's sarcoma, 43 peripheral primitive neuroectodermal tumor, and 5 Askin tumor. Median follow-up time was 31.5 months (range, 10-137 months). Thirty-eight patients received multidisciplinary therapy and 19 single model therapy in non-metastasis group. Three-year overall survival (OS) and event-free survival (EFS) were significantly different between non-metastatic multidisciplinary therapy group and non-metastatic single model group (63% vs. 20%, 46% vs. 18%, respectively, P<0.001). The patients who received surgery plus chemotherapy and plus radiation or not had longer survival than those treated with chemotherapy plus radiation in non-metastatic multidisciplinary therapy group (Chi2=7.591, 9.212; P=0.006, 0.002). CAV/IE alternative regimen was superior to other regimens in event-free survival, but not in overall survival (Chi2=6.950, 3.530; P=0.008, 0.06). Cox regression analysis suggested therapy model and response to treatment were independent prognostic factors for ESFT. CONCLUSIONS: Our studying showed multidisciplinary therapy could significantly improve non-metastatic ESFT patients' survival. Chemotherapy plus surgery and plus radiation or not were superior to chemotherapy plus radiation in local control for the non-metastatic ESFT. Therapy model and response were independent prognostic factors.

[Efficacy of modified B-NHL-BFM-90 protocol on anaplastic T-cell lymphoma in children and adolescents].

BACKGROUND AND OBJECTIVE: Anaplastic T-cell lymphoma in children and adolescents is an aggressive malignant non-Hodgkin's lymphoma (NHL). The optimal treatment regimen needs to be investigated. This study was to evaluate the efficacy of modified B-NHL-BFM-90 protocol on anaplastic T-cell lymphoma in children and adolescents. METHODS: From October 2002 to January 2008, 18 untreated anaplastic T-cell lymphoma patients aged less than 16 years were enrolled, and treated with modified B-NHL-BFM-90 protocol including cyclophosphamide, vincristine, ifosfamide, etoposide, adriamycin, HD-methotrexate, vindesine, dexamethasone, cytarabine/HD-cytarabine. Intrathecal injection was given every course. RESULTS: Of the 18 patients, 15 (83.3%) achieved complete remission (CR), and three (16.7%) achieved partial remission (PR). The patients were followed up for 4-68 months (median, 31 months). The 3-year event-free survival (EFS) rates were (87.4+/-8.4)% for all patients, 100% for stage II patients, and (85.1+/-9.7)% for stage III/IV patients; 100% for low risk group, (88.9+/-10.5)% for moderate risk group, and (80.0+/-17.9)% for high risk group. Most patients suffered from grade 3-4 myelosuppression and recovered after active support care. One patient with stage IV disease received autologous peripheral blood stem cell transplantation (PBSCT) after CR and was still alive. Two patients had tumor relapsed and died at three and five months after off treatment, respectively. CONCLUSIONS: Modified B-NHL-BFM-90 protocol, with tolerable toxicity, is an effective treatment regimen for anaplastic T-cell lymphoma in children and adolescents. It should be used in experienced cancer centers and hematological units.

[Correlation of tumor vessel function to synergistic antitumor effect of Avastin combined cyclophosphamide].

BACKGROUND & OBJECTIVE: Dysfunction of tumor vessels renders high interstitial pressure, hypoxia and acidosis, causing the barrier of cytotoxic efficacy of chemotherapeutic agents. This study was to observe the dynamic alteration of vessel function in neuroblastoma (NB) after treatment of Avastin, and explore the correlation of tumor vessel function to synergistic antitumor effect of Avastin plus cyclophosphamide (CPM). METHODS: Human NB cells were incubated and transplanted into nude mice to form NB xenografts. Avastin at a dose of 5 mg/kg was administered to the mice through the tail veins. The mice were killed on the 6th hour, 3rd day, 6th day and 9th day after Avastin treatment, separately. Tumor vessel function was tested with fluorescein Hoechst33342 staining. NB-bearing mice were treated with Avastin plus CPM. The synergistic antitumor effects were compared when CPM was administered simultaneously with Avastin (combined regimen I) or at the time the tumor vessel function was mostly improved after Avastin administration (combined regimen II). RESULTS: The tumor vessel function was mostly improved on the 6th day after Avastin treatment. Tumor inhibition rates were 36.4% in Avastin monotherapy group, 38.2% in CPM monotherapy group, 55.9% in combined regimen I group, and 66.8% in combined regimen II group at 3 weeks after treatment. The synergistic antitumor effect was better when CPM was administered on the 6th day after Avastin treatment as compared with it used simultaneously with Avastin (P<0.05). CONCLUSION: The synergistic antitumor effect can be augmented when CPM is administered at the time the tumor vessel function is mostly improved after Avastin treatment.

[Dynamic changes of serum proteomic spectra in patients with non-Hodgkin's lymphoma (NHL) before and after chemotherapy and screening of candidate biomarkers for NHL].

BACKGROUND & OBJECTIVE: Although the complete response rate of non-Hodgkin's lymphoma (NHL) is 70%-80% using modern comprehensive treatments, its relapse rate is about 40%-50%. The minimal residual disease (MRD) may be the reason of recurrence. This study was to detect dynamic changes of serum proteomic spectra in NHL patients before and after chemotherapy, thus to screen candidate markers for NHL. METHODS: The proteomic spectra from serum of 44 NHL patients before chemotherapy, 44 NHL patients who achieved complete remission (CR) after chemotherapy, and 51 healthy individuals were analyzed by surface-enhanced laser desorption/ ionization time of flight mass spectrometry (SELDI-TOF-MS) and Ciphergen ProteinChip 3.1 software. RESULTS: Compared with the normal group, one protein peak (M11710) was up-regulated in untreated NHL group, while was close to the normal level in CR group (P < 0.05); nine other protein peaks (M3322, M4355, M6445, M6646, M8581, M8708, M8918, M13959, M15149) were down-regulated in untreated NHL group, while were close to normal levels in CR group(P < 0.05). Five candidate biomarkers for NHL were screened using the decision tree model. CONCLUSIONS: Expressions of serum proteomic spectra are different before and after chemotherapy in NHL patients. Protein signatures of NHL may be screened using SELDI mass spectrometry combined with ProteinChip software. Those signatures may be helpful in screening MRD, detecting early recurrence and predicting the response to treatments.

[Treatment outcome of primary central nervous system germ cell tumors after combined therapy: a report of 23 cases].

BACKGROUND & OBJECTIVE: Primary central nervous system (CNS) germ cell tumors (GCTs) are rare malignant neoplasms with various histological types. Excluding pure germinoma and mature teratoma, other types carry a poor prognosis. Previous investigations focused on combined modality treatment including chemotherapy to improve survival. This study was to analyze the efficacy and toxicity of chemotherapy combined with surgery and/or radiotherapy on CNS GCTs. METHODS: A total of 23 patients with CNS GCTs were treated in Cancer Center of Sun Yat-sen University from May 2002 to Jun. 2006. The median age at diagnosis was 16 years. Alpha-fetoprotein (AFP) and/or beta-human chorionic gonadotropin (beta-HCG) levels were elevated in 19 patients (82.6%). All patients were treated with chemotherapy of PEB regimen combined with surgery and/or radiotherapy. PEB regimen was administered every 3 weeks with 20 mg/m(2) cisplatin (DDP) at Days 1-5 or 80-100 mg/m(2) at Day 1, 60-100 mg/m(2) etoposide (VP-16) or teniposide (VM-26) at Days 1-5, 10 mg/m(2) bleomycin (BLM) at Days 1 and 5. RESULTS: Of the 23 patients, 17 newly diagnosed patients received induction chemotherapy followed by radiotherapy or surgery/radiotherapy followed by adjuvant chemotherapy; 6 recurrent patients received salvage chemotherapy, of which 3 patients with disseminated tumor received salvage chemotherapy followed by craniospinal irradiation. The 23 patients completed a total of 61 cycles of PEB regimen with a median of 3 cycles. Chemotherapy alone gained a response rate of 87.0% and a complete remission rate of 30.4%. Craniospinal irradiation was performed in 14 patients and focal irradiation in 8 patients. One patient did not receive irradiation. Incomplete tumor resection or biopsy was performed in 13 patients. Fourteen patients (60.9%) were alive without evidence of diseases after combined modality treatment. With a median follow-up of 24 months, the 2-year survival rate was 67.4%. Main adverse events were late irradiation injury including aplastic anemia and hypothalamus syndrome (1 case), irradiation encephalopathy (1 case), and hypopituitarism (2 cases). CONCLUSIONS: The combined modality treatment including PEB regimen is highly effective in treating CNS GCTs patients, especially in the patients with elevated tumor markers. However, the long-term toxicities which related with craniospinal irradiation should not be ignored.

Intensive chemotherapy improved treatment outcome for Chinese children and adolescents with lymphoblastic lymphoma.

BACKGROUND: Lymphoblastic lymphoma (LBL) is a highly aggressive lymphoma, for which intensive chemotherapy is necessary. This study was designed to evaluate the efficacy and toxicity of a modified acute lymphoblastic leukemia (ALL)-Berlin-Frankfurt-Münster (BFM)-90-based protocol in Chinese children and adolescents with LBL. METHODS: From March 1998 to November 2006, 60 untreated patients with LBL (age <18 years) from a single institution were enrolled. All patients were treated with the modified ALL-BFM-90 protocol, and prophylactic cranial radiotherapy was omitted. RESULTS: The median age of the patients was 10 years (range, 2.5-18 years). Forty-eight (80%) patients had T-cell LBL, and 59 (98.3%) of the patients were stage III/IV. At the end of induction remission Ia (day 33), 3 patients had died of treatment-related toxicity. In the remaining 57 patients, complete remission (CR) or CR undetermined (CRu) had occurred in 47 (82.45%), who were designated as the moderate-risk group and partial remission (PR) had occurred in 10 patients (17.54%), who were designated the high-risk group. All patients experienced grade 3-4 hematological toxicity. At a median follow-up of 35 months, event-free survival was 78.81%+/-0.05 for all patients; the figure was 88.34%+/-0.05 for the moderate-risk group (90.91%+/-0.08 for stage III, 87.68%+/-0.06 for stage IV, 100% for those with B-cell LBL, 84.78%+/-0.06 for those with T-cell LBL, and 82.94%+/-0.08 for stage IV patients with more than 25% blast cells in bone marrow [BM]). The event-free survival in the high-risk group was 60%+/-0.15. CONCLUSION: This modified ALL-BFM-90 protocol is an effective regimen and it greatly improved the survival rate of Chinese children and adolescents with LBL compared with the ALL protocols used previously.

[Clinical analysis of 69 cases of Burkitt's lymphoma].

BACKGROUND & OBJECTIVE: Burkitt's lymphoma is a kind of highly aggressive B-cell lymphoma. Its clinical characteristics are different between the endemic areas in Africa and the sporadic areas in America and Europe. There is no large-scale report concerning Burkitt's lymphoma in China yet. This study was to summarize the characteristics of Burkitt's lymphoma in China. METHODS: Clinical data of 69 Burkitt's lymphoma patients, treated from May 1985 to May 2007 in Cancer Center of Sun Yat-sen University, were analyzed. RESULTS: Of the 69 patients, 44 were men and 25 were women, with a median age of 7 (range, 2-72); 5 were at stage I, 9 at stage II, 21 at stage III, and 34 at stage IV, advanced stage (stages III and IV) accounted for 55 (79.7%) patients. Abdomen (63.8%), cervical lymph nodes (68.1%) and faciomaxillary-oropharynx (34.8%) were the most common involved sites. Bone marrow (21.9%) and central nervous system (17.4%) could also be involved. B symptoms were found in 34 patients. Serum lactate dehydrogenase (LDH) level was elevated in 42 of 58 patients, while serum uric acid level was elevated in 13 of 56 patients. Hepatitis B virus (HBV) infection was found in 6 of 57 patients, Epstain-Barr virus (EBV) infection in 7 of 13 patients, human immunodeficiency virus (HIV) infection in 0 of 51 patients. Short-term and high intensive chemotherapy with central nervous system prophylaxis could improve the prognosis. CONCLUSION: The clinical characteristics of these 69 Burkitt's lymphoma patients are much similar to those from sporadic areas, but the median age is lower, and the most common involved sites are cervical lymph nodes, abdomen and faciomaxillary-oropharynx.

[Bone marrow immunophenotypes of 112 cases of lymphoid system malignant diseases].

BACKGROUND & OBJECTIVE: Diagnosis of lymphocytic leukemia and non-Hodgkin's lymphoma (NHL) is based on bone marrow morphology. Immunophenotyping will make diagnosis more precise through analyzing the origin and differentiation status of tumor, which is necessary for treatment and prognosis prediction. This study was to analyze the immunophenotypic characteristics of lymphocytic leukemia and NHL with bone marrow involvement using flow cytometry (FCM). METHODS: Bone marrow specimens from 112 patients with lymphocytic leukemia or NHL with bone marrow involvement were detected by FCM using antibodies of T, B and myeloid cell series. Using CD45/SSC gating strategy, the samples were analyzed with 5 parameters (FSC, SSC, McAb1-FITC, McAb2-PE, CD45-cytochrome). RESULTS: In 45 cases of precursor B lymphoblastic leukemia/lymphoma (B-ALL/LBL), the antigens were mainly CD19, CD10, TdT, CD34, HLA-DR, and CD20. In 32 cases of precursor T lymphoblastic leukemia/lymphoma (T-ALL/LBL), the antigens were mainly CD7, CD5, cytoplasmic (Cy)CD3, TdT, CD34, surface CD3 (sCD3), and HLA-DR. Of the 77 cases of precursor ALL/LBL, 28(36.4%) expressed myeloid-associated antigens, such as CD13 and CD33; 9 (20.0%) cases of B-ALL/LBL coexpressed CD20 and CD34; 28(87.5%) cases of T-ALL/LBL coexpressed cyCD3 and TdT. Among the 35 cases of mature B-cell malignancies, 17 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) mainly expressed CD19, CD20, CD5, HLA-DR, with coexpression of CD19 and CD5; 4 cases of diffuse large B-cell lymphoma (DLBCL) mainly expressed CD19, CD20, CD10, and HLA-DR; 3 cases of Burkitt's lymphoma (BL) mainly expressed CD19, CD10, CD20, and sIgM; 1 case of mantle cell lymphoma (MCL) expressed CD5, CD19, CD20, and HLA-DR. Among the 10 mature T-cell malignancies, 5 cases of unspecialied peripheral T-cell lymphoma (PTCL) mainly expressed sCD3, CD5 and CD7, CD4 or CD8; 1 case of anaplastic large cell lymphoma (ALCL) expressed sCD3 and HLA-DR; 4 cases of NK/T-cell malignancies expressed CD56 and HLA-DR, CD4 or CD8 or CD7. Mature lymphoid system malignancies didn't express early antigens, such as CD34 and TdT, but expressed myeloid-associated antigens, especially CD13 and CD33. CONCLUSION: Multiparameter FCM can not only provide data of cell lineage and differentiation status but also detect phenotypic aberrancies, which is helpful for minimal residual disease detecting.

[Feasibility to treat pediatric cancer pain with analgesics for adults and their efficacy].

BACKGROUND & OBJECTIVE: Lacking enough knowledge of pediatric cancer pain and pediatric dosage form of analgesics, current treatment of pediatric cancer pain in China is unsatisfactory. This study was to probe the efficacy and safety of treating pediatric cancer pain with analgesics for adults through summarizing the experience of diagnosis and treatment in Cancer Center of Sun Yet-sen University. METHODS: Basing on the components and the endurable dosage of each component for children, we formulated the appropriate dosage and usage of a few analgesics (including sustained release tablets of morphine, oxycodone and transdermal fantanyl) available in China, most of which were used in adults. Cancer pain of 139 children with newly diagnosed tumors were treated according to the World Health Organization (WHO) analgesic ladder, including 19 cases of mild pain, 41 cases of moderate pain and 79 cases of severe pain. Efficacy and adverse events were evaluated. RESULTS: Of the 139 patients, 104 (74.8%) were treated with analgesics of 1 WHO ladder step, 35 (25.2%) were treated with increased WHO ladder steps (ladder 1-->2 or 2-->3) or reduced WHO ladder steps (ladder 3-->2 or 2-->1). The total response rate for pain relief was 100%: 129 (92.8%) patients had complete relief, 7 (5.0%) had obvious relief, 3(2.2%) had moderate relief. The median time for pain control was 5 days (range, 1-12 days). Sustained release tablets of morphine, transdermal fantanyl, and sustained release tablets of oxycodone were used in 20, 28, and 40 patients, respectively. The median ages of the 3 groups were 10 (5-18), 6 (2.3-16), and 5 (2.5-16) years, respectively. The median of maximum dosages of the 3 single drugs were 20 (10-70) mg, 25 (12.5-50) microg/h, and 10 (5-30) mg, respectively. The median doses used in the 3 groups were 100 (20-360) mg, 5 (1.25-7.5) mg, and 60 (10-200) mg, respectively. The non-steroid anti-inflammatory drug-induced adverse events were nausea and vomiting with very low frequencies. The weak opioid and strong opioid drug-induced adverse events included constipation, nausea, vomiting, and somnolence, all of which were reversible. No severe adverse events, including respiratory depression and drug addiction, happened. CONCLUSIONS: The WHO ladder approach for cancer pain is appropriate for children. Currently in China, most analgesics for adults could be used for pediatric cancer pain treatment.

[Efficacy of modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in Chinese children and adolescents].

BACKGROUND & OBJECTIVE: Burkitt's lymphoma is an aggressive non-Hodgkin's lymphoma (NHL) and often involves bone marrow and central nerve system. The efficacy of CHOP regimen on Burkitt's lymphoma is poor. The optimal chemotherapy regimen needs to be investigated. This study was to evaluate the efficacy of modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in children and adolescents, and observe the survival status. METHODS: From Oct. 1999 to Nov. 2006, 31 untreated Burkitt's lymphoma patients aged less than 20 were enrolled. The median age of these patients was 5 (range, 1.5-20 years old). Of the 31 patients, 20 (64.5%) were male, 11 (35.5%) were female. According to St Jude staging system, 1 (3.2%) was at stage I, 6 (19.4%) at stage II, 8 (25.8%) at stage III, 16 (51.6%) at stage IV; 24 (77.4%) were at stage III/IV. According to clinical stage, lactate dehydrogenase (LDH) level and treatment response, these patients were divided into low, moderate and high risk groups. They received modified B-NHL-BFM-90 protocol: cytotoxic drugs such as cyclophosphamide, vincristine, ifosfamide, etoposide, adriamycin, HD-methotrexate, vindesin, dexamethasone, cytarabinec/HD-cytarabine and intrathecal injection. RESULTS: One patient died of tumor lysis syndrome during prophase. The efficacy was evaluable in 30 patients. Of the 30 patients, 25 (83.3%) achieved complete remission (CR), 3 (10.0%) achieved partial remission (PR), 2 (6.7%) had progressive disease (PD)û 1 had tumor relapse. Grade 3-4 myelosuppression occurred in most patients and were recovered by active support care and did not affect next course of chemotherapy. At a median follow-up of 33 months (range, 3-98 months), the 3-year event-free survival (EFS) rate was 86.0% for all patients, with 100% for stage I/II patients and 82.1% for stage III/IV patients, 100% for low risk group, 92.0% for moderate risk group, and 70.0% for high risk group. CONCLUSIONS: Modified B-NHL-BFM-90 protocol can improve the responses and survival of Burkitt's lymphoma in Chinese children and adolescents, with tolerable toxicity. It should be used in the experienced cancer center and hematological unit.

[Efficacy of chemotherapy regimen using ifosphamide and carboplatin on recurrent or refractory neuroblastoma].

BACKGROUND & OBJECTIVE: About 30% of neuroblastoma patients have poor response to first-line chemotherapy or progress during chemotherapy. Although advanced neuroblastoma patients could achieve complete remission after combined treatment, most of them relapsed finally. This study was to evaluate the efficacy of ifosphamide and carboplatin as a salvage chemotherapy regimen on recurrent or refractory neuroblastoma. METHODS: Nine refractory neuroblastoma patients and 23 recurrent neuroblastoma patients were treated with ifosphamide (1.5 g/m(2) daily for 5 days) and carboplatin (400 mg/m(2) on day 1). Mesna was applied at a dosage of 20% of ifosfamide 3 times at 4-hour intervals after termination of the ifosfamide infusion. Chemotherapy was administered every 2-3 weeks. RESULTS: None of the 32 patients achieved complete remission; 19 (59.4%) achieved partial remission. The median remission time was 4.2 months (1-28 months). After chemotherapy, 8 patients received operation to resect tumors. Main adverse events included grade III-IV neutropenia (44.7%), grade III-IV thrombocytopenia (53.1%), neutropenia accompanied with infection (18.8%), grade I liver dysfunction (12.5%), and hemorrhagic cystitis (9.4%). All adverse events were reversible. CONCLUSIONS: Recurrent and refractory neuroblastoma responds well to chemotherapy regimen of ifosphamide plus carboplatin. The toxicities are tolerable. But the long-term prognosis is poor. More effective strategies are needed to improve its long-term survival.

[Clinical analysis of reactive thymic hyperplasia following chemotherapy for childhood malignant lymphoma].

BACKGROUND & OBJECTIVE: Reactive thymic hyperplasia following chemotherapy for malignant tumors is likely to be misdiagnosed as tumor residue or relapse, therefore, leads to unnecessary treatment. This study was to analyze the clinical features of reactive thymic hyperplasia following chemotherapy for childhood malignant lymphoma. METHODS: Clinical data of 13 children with reactive thymic hyperplasia following chemotherapy for malignant lymphoma, treated from Mar. 1999 to Mar. 2004, were retrospectively analyzed. Of the 13 cases, 5 were Hodgkin's disease (HD), and 8 were non-Hodgkin's lymphoma (NHL). All patients received computed tomography (CT) to evaluate the therapeutic effect. When a new thymic mass emerged, positive electron tomography/computed tomography (PET/CT) was performed to identify its quality. RESULTS: At diagnosis, 10 patients had mediastinal involvement. Reactive thymic hyperplasia occurred following the completion of chemotherapy in 9 cases, or during the maintenance of chemotherapy in 4 cases. CT showed that the longest diameters of the new mediastinal masses were 2.2-6.0 cm (mean 3.7 cm). The interval from last chemotherapy cycle to the occurrence of thymic hyperplasia was 2-12 months (mean 4 months). PET/CT was performed to 5 cases, and showed no vital tumors in the mediastinum. Three cases were misdiagnosed as tumor residue or relapse, and received second-line therapy. All patients were followed-up for 1-6 years (median 4 years), and none suffered tumor relapse. CONCLUSIONS: Reactive thymic hyperplasia may occur following intensive chemotherapy for childhood malignant lymphoma. It should not be misdiagnosed as malignant tumors and overtreated.