Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Vincristine and dexamethasone pulses in addition to maintenance therapy among pediatric acute lymphoblastic leukemia (GD-ALL-2008): An open-label, multicentre, randomized, phase III clinical trial.

The efficacy and safety on the addition of vincristine (VCR) and dexamethasone (DEX) pulses to maintenance therapy among childhood acute lymphoblastic leukemia (ALL) remain uncertain. Herein, we perform an open-label, multicentre, randomized, phase III clinical trial that was conducted at nine major medical centers in Guangdong Province, China. Patients were randomly assigned either the conventional maintenance therapy (control group, n = 384) or the VCR/DEX pulse (treatment group, n = 375). When limited to the SR cohort, 10-year EFS was 82.6% (95% CI: 75.9-89.9) in the control group and 80.7% (95% CI: 74-88.1) in the treatment group (pnon-inferiority  = .0002). Similarly, patients with IR also demonstrated non-inferiority of the treatment group to the control group in terms of 10-year EFS (73.6% [95% CI: 67.6-80] vs. 77.6% [95% CI: 71.8-83.9]; pnon-inferiority  = .005). Among the HR cohort, compared with the control group, patients in the treatment group experienced a significant benefit in terms of 10-year EFS (61.1% [95% CI: 47.7-78.2] vs. 72.6% [95% CI: 55.6-94.7], p = .026) and a trend toward higher 10-year OS (73.8% [95% CI: 61.6-88.4] vs. 87.9% [95% CI: 579.2-97.5], p = .068). In the HR cohort, the total rate of drug-induced liver injury and Grade 3 chemotherapy-induced anemia were both lower for patients in the treatment group than in the control group (55.6% vs. 100%, p = .033; 37.5% vs. 60%, p = .036). Conversely, the total prevalence of chemotherapy-induced thrombocytopenia was higher for patients in the treatment group than in the control group (88.9% vs. 40%, p = .027). Pediatric acute lymphoblastic leukemia with high risk is suitable to VCR/DEX pulse during maintenance phase for the excellent outcome, while the standard-to-intermediate-risk patients could eliminate the pulses.

Prognostic significance of CNSL at diagnosis of childhood B-cell acute lymphoblastic leukemia: A report from the South China Children's Leukemia Group.

Objectives: The prognostic significance of acute lymphoblastic leukemia (ALL) patients with central nervous system leukemia (CNSL) at diagnosis is controversial. We aimed to determine the impact of CNSL at diagnosis on the clinical outcomes of childhood B-cell ALL in the South China Children's Leukemia Group (SCCLG). Methods: A total of 1,872 childhood patients were recruited for the study between October 2016 and July 2021. The diagnosis of CNSL depends on primary cytological examination of cerebrospinal fluid, clinical manifestations, and imaging manifestations. Patients with CNSL at diagnosis received two additional courses of intrathecal triple injections during induction. Results: The frequency of CNLS at the diagnosis of B-cell ALL was 3.6%. Patients with CNSL at diagnosis had a significantly higher mean presenting leukocyte count (P = 0.002) and poorer treatment response (P <0.05) compared with non-CNSL patients. Moreover, CNSL status was associated with worse 3-year event-free survival (P = 0.030) and a higher risk of 3-year cumulative incidence of relapse (P = 0.008), while no impact was observed on 3-year overall survival (P = 0.837). Multivariate analysis revealed that CNSL status at diagnosis was an independent predictor with a higher cumulative incidence of relapse (hazard ratio = 2.809, P = 0.016). Conclusion: CNSL status remains an adverse prognostic factor in childhood B-cell ALL, indicating that additional augmentation of CNS-directed therapy is warranted for patients with CNSL at diagnosis.

Comparison of Long-Term Outcomes and Sequelae Between Children and Adult Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy.

PURPOSE: Our purpose was to compare long-term survival outcomes and sequelae between child and adult nasopharyngeal carcinoma (NPC) in the era of intensity modulated radiation therapy. METHODS AND MATERIALS: Data on 285 patients with NPC aged ≤18 years at diagnosis and treated with intensity modulated radiation therapy between January 2004 and November 2016 were retrospectively reviewed. A propensity score matching method was adopted to screen matched adult patients with NPC at a ratio of 1:3. Survival outcomes and treatment-related toxicities between child and adult groups were compared. RESULTS: In total, 159 children and 477 adult patients with NPC were included in this study. The 5-year overall survival, distant metastasis-free survival, locoregional relapse-free survival, and disease-free survival between children and adults were 89.2% versus 83.6% (P = .144), 88.7% versus 83.5% (P = .124), 96.4% versus 89.1% (P = .013), and 86.5% versus 77.3% (P = .021), respectively. Subgroup analyses revealed that the young age was an independent prognostic factor of overall survival, distant metastasis-free survival, and locoregional relapse-free survival in the advanced N stage (N2-3) group and disease-free survival in the advanced T stage (T3-4) group and N2-3 and stage III-IVA groups. The most common sequela was ototoxicity (68.9%) in child patients and xerostomia (70.8%) in adult patients. Adult survivors had a significantly higher incidence of grade 3 to 4 late toxicities in xerostomia (17.6% vs 8.9%; P = .004), skin dystrophy (9.3% vs 3.7%; P = .022), neck fibrosis (8.3% vs 4.4%; P < .001), and radiation encephalopathy (0.8% vs 0; P = .006). Child survivors were more likely to develop grade 3 to 4 growth retardation and endocrine insufficiency (3.0% vs 0.3%; P = .014). CONCLUSIONS: Child patients with NPC achieved significantly better survival outcomes but fewer late toxicities than adult patients. However, we should pay great attention to growth problems of child survivors.

Brain metastasis in children with stage 4 neuroblastoma after multidisciplinary treatment.

INTRODUCTION: Brain metastasis is common in relapsed neuroblastoma patients, but the characteristics of brain metastasis remain largely unknown. This study aimed to investigate the status of brain metastasis with neuroblastoma in South China. METHODS: In this retrospective case-based study, 106 patients with stage 4 neuroblastoma from the Department of Pediatric Oncology in Sun Yat-sen University Cancer Center between January 2004 and May 2013 were included. The incidence, risk factors, and survival status of these patients were reviewed and analyzed. RESULTS: Of the 106 patients, 11 (10.4%) developed brain metastasis, accounting for 20.0% of 55 patients with relapse or progression. The age at initial diagnosis of the 11 patients ranged from 2 to 10 years (median 4 years), which was younger than that of the patients without brain metastasis (median 5 years, range 1-10 years, P=0.073). The male to female ratio of the 11 patients was 8:3, which was not significantly different from that of the patients without brain metastasis (P=0.86). Patients with brain metastasis had higher lactate dehydrogenase levels than those without brain metastasis, but the differences were not significant (P=0.076). Eight patients died, and 3 patients survived. The median interval from the initial diagnosis to the development of brain metastasis was 18 months (range 6-32 months). The median survival was 4 months (range 1 day to 29 months) after the diagnosis of brain metastasis. The median interval from the manifestation of brain metastasis to death was 3 months (range 1 day to 11 months). CONCLUSIONS: High-risk factors for brain metastasis in cases of neuroblastoma include bone marrow involvement and a younger age at initial diagnosis. Nevertheless, multiple treatment modalities can improve disease-free survival.

Survival analysis of children with stage II testicular malignant germ cell tumors treated with surgery or surgery combined with adjuvant chemotherapy.

For children with stage II testicular malignant germ cell tumors (MGCT), the survival is good with surgery and adjuvant chemotherapy. However, there is limited data on surgical results for cases in which there was no imaging or pathologic evidence of residual tumor, but in which serum tumor markers either increased or failed to normalize after an appropriate period of half-life time post-surgery. To determine the use of chemotherapy for children with stage II germ cell tumors, we analyzed the outcomes (relapse rate and overall survival) of patients who were treated at the Sun Yat-sen University Cancer Center between January 1990 and May 2013. Twenty-four pediatric patients with a median age of 20 months (range, 4 months to 17 years) were enrolled in this study. In 20 cases (83.3%), the tumors had yolk sac histology. For definitive treatment, 21 patients underwent surgery alone, and 3 patients received surgery and adjuvant chemotherapy. No relapse was observed in the 3 patients who received adjuvant chemotherapy, whereas relapse occurred in 16 of the 21 patients (76.2%) treated with surgery alone. There were a total of 2 deaths. Treatment was stopped for 1 patient, who died 3 months later due to the tumor. The other patient achieved complete response after salvage treatment, but developed lung and pelvic metastases 7 months later and died of the tumor after stopping treatment. For children treated with surgery alone and surgery combined with adjuvant chemotherapy, the 3-year event-free survival rates were 23.8% and 100%, respectively (P = 0.042), and the 3-year overall survival rates were 90.5% and 100%, respectively (P = 0.588). These results suggest that adjuvant chemotherapy can help to reduce the recurrence rate and increase the survival rate for patients with stage II germ cell tumors.

The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors.

Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.

[Outcome of children and adolescents with Burkitt lymphoma and diffuse large B cell lymphoma treated with a modified NHL-BFM-90 protocol].

OBJECTIVE: To evaluate the efficacy of a modified NHL-BFM-90 protocol in childhood and adolescence with Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 138 de novo patients with BL and DLBCL were enrolled. All patients were stratified into low (R1), intermediate (R2) and high risk (R3) groups based on the stage, chemotherapy response and LDH level, and treated with a modified NHL-BFM 90 protocol. RESULTS: Of the 138 patients, 105 were boys and 33 girls, with a median age at diagnosis of 7.5 yr (range 1.5 to 20.0 yr). Eighty-two cases were BL, 56 cases DLBCL. The patients with stage III/IV accounted for 76.1%. Thirty-one patients were assigned to group R1, 38 patients group R2, and 69 patients group R3. Complete remission (CR) after chemotherapy was 90.6%. At a median follow-up of 50 months(1-158 months), a total of 19 patients died of disease. The 5-year event free survival (EFS) and overall survival (OS) for the entire group were 85.8%, 85.8% respectively. 5-year EFS was 97.1% for stage I/II, 82.1% for stage III/IV respectively (P=0.039); and 96.7%, 86.8% and 80.2% for groups R1, R2 and R3 respectively (P=0.135); and 85.2% and 86.9% for BL and DLBCL respectively (P=0.635). Major toxicity was myelosuppression, which was tolerant and manageable. CONCLUSION: That the modified NHL-BFM-90 protocol was highly effective for children and adolescents with BL and DLBCL, and especially improved the survival of the advanced patients.

Lymphoma and cerebral vasculitis in association with X-linked lymphoproliferative disease.

Lymphoma is seen in up to 30% of patients with X-linked lymphoproliferative disease (XLP), but cerebral vasculitis related with XLP after cure of Burkitt lymphoma is rarely reported. We describe a case of a 5-year-old boy with XLP who developed cerebral vasculitis two years after cure of Burkitt lymphoma. He had Burkitt lymphoma at the age of 3 years and received chemotherapy (non-Hodgkin's lymphoma-Berlin-Frankfurt-Milan-90 protocol plus rituximab), which induced complete remission over the following two years. At the age of 5 years, the patient first developed headache, vomiting, and then intellectual and motorial retrogression. His condition was not improved after anti-infection, dehydration, or dexamethasone therapy. No tumor cells were found in his cerebrospinal fluid. Magnetic resonance imaging showed multiple non-homogeneous, hypodense masses along the bilateral cortex. Pathology after biopsy revealed hyperplasia of neurogliocytes and vessels, accompanied by lymphocyte infiltration but no tumor cell infiltration. Despite aggressive treatment, his cognition and motor functions deteriorated in response to progressive cerebral changes. The patient is presently in a vegetative state. We present this case to inform clinicians of association between lymphoma and immunodeficiency and explore an optimal treatment for lymphoma patients with compromised immune system.

Safety of in vitro amplified HLA-haploidentical donor immune cell infusions for childhood malignancies.

In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children. Therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×10(8) immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies.

Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma: a report of 76 cases.

Pediatric diffuse large B-cell lymphoma (DLBCL) is a highly aggressive disease with unique clinical characteristics. This study analyzed the germinal-center type B-cell (GCB) classification and clinical characteristics of Chinese pediatric DLBCL. A total of 76 patients with DLBCL newly diagnosed in Sun Yat-sen University Cancer Center between February 2000 and May 2011, with an age younger than 18 years, were included in the analysis. The male/female ratio was 3.47:1. The median age was 12 years (range, 2 to 18 years), and 47 (61.8%) patients were at least 10 years old. Of the 76 patients, 48 (63.2%) had stage III/IV disease, 9 (11.8%) had bone marrow involvement, 1 (1.3%) had central nervous system (CNS) involvement, and 5 (6.6%) had bone involvement. The GCB classification was assessed in 45 patients: 26 (57.8%) were classified as GCB subtype, and 19 (42.2%) were classified as non-GCB subtype. The modified B-NHL-BFM-90/95 regimen was administered to 50 patients, and the 4-year event-free survival (EFS) rate was 85.8%. Among these 50 patients, 31 were assessed for the GCB classification: 17 (54.8%) were classified as GCB subtype, with a 4-year EFS rate of 88.2%; 14 (45.2%) were classified as non-GCB subtype, with a 4-year EFS rate of 92.9%. Our data indicate that bone marrow involvement and stage III/IV disease are common in Chinese pediatric DLBCL patients, whereas the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB subtype. The modified B-NHL-BFM-90/95 protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.

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.

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.

[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.

[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.

[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.

[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.

[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.

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.

[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.