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1.
Cancer Med ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31994344

RESUMO

BACKGROUND: Septicemia is an important cause of treatment-related mortality and treatment failure in pediatric acute lymphoblastic leukemia (ALL) in developing countries. A multicenter CCCG-ALL-2015 study was conducted in China and factors associated with septicemia and mortality were studied. METHODS: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included. Patients with documented septicemia were identified from the Data Center and additional data were collected. RESULTS: A total of 4080 patients were recruited in the study and 527 patients with septicemia were identified (12.9%, 95% CI 11.9%-13.9%). The intermediate risk (IR)/high risk (HR) group had significantly higher incidence of septicemia as compared with low risk (LR) group, 17.1% vs 9.1% (OR 2.07, 95% CI 1.71-2.49, P < .001). Induction phase was the period with majority of septicemia episodes happened, 66.8% in LR and 56.1% in IR/HR groups. Gram-positive bacteria accounted for 54.1%, gram-negative bacteria 44.5%, and fungus 1.4% of positive cultures. Multidrug-resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.4% (95% CI 1.9%-4.9%). Multiple logistic regression identified female gender, comorbid complications, and fungal infection as risk factors associated with mortality. Gram-negative septicemia was associated with higher mortality, 4.9% vs 1.4% (OR 0.28, 95% CI 0.09-0.88, P = .02). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%. CONCLUSION: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to the reports of western countries. The septicemia-related mortality rate was low. There was marked variation in the incidence of septicemia among the centers.

2.
JAMA Oncol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31944221

RESUMO

Importance: A randomized clinical trial is needed to determine whether the second-generation Abl-tyrosine kinase inhibitor dasatinib is more effective than the first-generation inhibitor imatinib mesylate for childhood Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). Objective: To determine whether dasatinib given at a daily dosage of 80 mg/m2 is more effective than imatinib mesylate at a daily dosage of 300 mg/m2 to improve event-free survival of children with Philadelphia chromosome-positive ALL in the context of intensive chemotherapy without prophylactic cranial irradiation. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial was conducted at 20 hospitals in China. Enrollment occurred from January 1, 2015, through September 18, 2018, and randomization was stopped on October 4, 2018, when the early stopping criterion of the trial was met. Patients aged 0 to 18 years were recruited. Of the 225 patients with the diagnosis, 35 declined participation and 1 died before treatment, leaving 189 patients available for analysis. Data were analyzed from January 1 through August 4, 2019. Interventions: Patients were randomized to receive daily dasatinib (n = 92) or imatinib (n = 97) continuously for the entire duration of ALL therapy from the time of diagnosis made during remission induction to the end of continuation therapy. Main Outcomes and Measures: The primary outcome was event-free survival, analyzed based on intention to treat. The secondary outcomes were relapse, death due to toxic effects, and overall survival. Results: Among the 189 participants (136 male [72.0%]; median age, 7.8 [interquartile range (IQR), 5.2-11.3] years) and a median follow-up of 26.4 (IQR, 16.3-34.1) months, the 4-year event-free survival and overall survival rates were 71.0% (95% CI, 56.2%-89.6%) and 88.4% (95% CI, 81.3%-96.1%), respectively, in the dasatinib group and 48.9% (95% CI, 32.0%-74.5%; P = .005, log-rank test) and 69.2% (95% CI, 55.6%-86.2%; P = .04, log-rank test), respectively, in the imatinib group. The 4-year cumulative risk of any relapse was 19.8% (95% CI, 4.2%-35.4%) in the dasatinib group and 34.4% (95% CI, 15.6%-53.2%) in the imatinib group (P = .01, Gray test), whereas the 4-year cumulative risk of an isolated central nervous system relapse was 2.7% (95% CI, 0.0%-8.1%) in the dasatinib group and 8.4% (95% CI, 1.2%-15.6%) in the imatinib group (P = .06, Gray test). There were no significant differences in the frequency of severe toxic effects between the 2 treatment groups. Conclusions and Relevance: Intensive chemotherapy including dasatinib at a dosage of 80 mg/m2 per day yielded superior results in the treatment of Philadelphia chromosome-positive ALL compared with imatinib mesylate at a dosage of 300 mg/m2 per day and provided excellent control of central nervous system leukemia without the use of prophylactic cranial irradiation. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-14005706.

3.
Blood ; 135(1): 41-55, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697823

RESUMO

To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial samples in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes (NR3C1, NR3C2, TP53, NT5C2, FPGS, CREBBP, MSH2, MSH6, PMS2, WHSC1, PRPS1, and PRPS2) involved in drug response. Their prevalence was 17% in very early relapse (<9 months from diagnosis), 65% in early relapse (9-36 months), and 32% in late relapse (>36 months) groups. Convergent evolution, in which multiple subclones harbor mutations in the same drug resistance gene, was observed in 6 relapses and confirmed by single-cell sequencing in 1 case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently a 2-step process in which a persistent clone survived initial therapy and later acquired bona fide resistance mutations during therapy. In contrast, very early relapses arose from preexisting resistant clone(s). Two novel relapse-specific mutational signatures, one of which was caused by thiopurine treatment based on in vitro drug exposure experiments, were identified in early and late relapses but were absent from 2540 pan-cancer diagnosis samples and 129 non-ALL relapses. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy-induced drug resistance mutations facilitate a subset of pediatric ALL relapses.

4.
Arch Dis Child ; 104(6): 522-529, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30705079

RESUMO

OBJECTIVES: Before 2003, most children with acute lymphoblastic leukaemia (ALL) abandoned treatment, with only approximately 30% treated in China. With the development of national insurance for underprivileged patients, we assessed the current frequency and causes of treatment abandonment among patients with ALL who were enrolled in the Chinese Children's Cancer Group ALL protocol between 2015 and 2016. METHODS: Demographic, clinical and laboratory data on patients who abandoned treatment, as well as economic and sociocultural data of their families were collected and analysed. General health-related statistics were retrieved from publicly accessible databanks maintained by the Chinese government. RESULTS: At a median follow-up of 119 weeks, 83 (3.1%, 95% CI 2.5% to 3.8%) of the 2641 patients abandoned treatment. Factors independently associated with abandonment included standard/high-risk ALL (OR 2.62, 95% CI 1.43 to 4.77), presence of minimal residual disease at the end of remission induction (OR 3.57, 95% CI 1.90 to 6.74) and low-income economic region (OR 3.7, 95% CI 1.89 to 7.05). According to the family members, economic constraints (50.6%, p=0.0001) were the main reason for treatment abandonment, followed by the belief of incurability, severe side effects and concern over late complications. CONCLUSIONS: The rate of ALL treatment abandonment has been greatly reduced in China. Standard/high-risk ALL, residence in a low-income region and economic difficulties were associated with treatment abandonment. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IPR-14005706, pre-results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , China , Feminino , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasia Residual , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Indução de Remissão , Estudos Retrospectivos , Fatores Socioeconômicos
5.
Int J Cancer ; 144(1): 117-124, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30098202

RESUMO

Langerhans cell histiocytosis (LCH) is the most common histiocytosis with constitutive activation of the RAS-RAF-MEK-ERK (MAPKinase) cell signaling pathway. We analyzed 89 cases of BRAF and MAP2K1 mutations by Sanger sequencing, of which 18 cases showed that these two gene mutations are negative. Whole genome sequencing of suitable specimens in these negative cases revealed a translocation from the 3 intron of PLEKHA6 to the 13 intron of NTRK3 in one case. We identified that this translocation could cause a novel fusion mutation, PLEKHA6-NTRK3. Overexpression of the PLEKHA6-NTRK3 mutant in NIH 3T3 cells enhanced MAPKinase pathway activation, promote cell growth. Our result suggested that a new mutation need be included in LCH molecular screening panel to better define its prevalence in LCH.


Assuntos
Histiocitose de Células de Langerhans/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Receptor trkC/genética , Proteínas Recombinantes de Fusão/genética , Adolescente , Animais , Proliferação de Células/genética , Criança , Pré-Escolar , Feminino , Histiocitose de Células de Langerhans/patologia , Humanos , Lactente , Masculino , Camundongos , Mutação , Células NIH 3T3
6.
Hematol Oncol ; 36(4): 679-688, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30133806

RESUMO

Long-term follow-up data for childhood acute lymphoblastic leukemia (ALL) are scarce in China because of lacking population-based and hospitalized registry system. This retrospective study, conducted at Shanghai's Children's Medical Center in China (SCMC), aimed to investigate the long-term results of childhood ALL and to identify prognostic factors. The Pediatric Oncology Network Database, designed by St. Jude Children's Research Hospital, USA, were used to collect data for the enrolled patients starting in 2005. From 2005 to 2014, 1085 evaluable patients with ALL aged 1 to 18 years old were enrolled and treated using SCMC-ALL-2005 risk-stratified protocol. Complete remission was achieved in 95.6% of patients. At 5 and 10 years, the event-free survival rate was 68.3 ± 1.4% and 64.6 ± 1.6%, and the overall survival rate was 80.0 ± 1.2% and 76.3 ± 1.6%, respectively. The 5-year event-free survival rates were 81.8 ± 2.0%, 67.0 ± 1.9%, and 14.3 ± 4.0% for patients in low-risk, intermediate-risk, and high-risk groups, respectively. The cumulative risk of relapse was 24.5% at 10 years. Induction failure conferred worse prognosis. Patients younger than 1 year of age at diagnosis, intermediate-risk/high-risk group, male gender, and positive minimal residual disease (MRD) results at day 55, both in the univariate and multivariate analysis, were associated with significantly worse prognosis (P < .05). Patients with positive MRD at both day 35 and day 55 were related to a significantly poor outcome (P < .0001), but not for patients with negitive MRD at day 35. The overall outcomes for ALL patients treated with protocol SCMC-ALL-2005 in SCMC are lower than in developed countries. Factors including age, gender, risk group and MRD results at day 55 were associated with treatment outcomes in childhood ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento
7.
J Cancer Res Clin Oncol ; 143(7): 1327-1335, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28283783

RESUMO

This retrospective study evaluated the long-term outcomes and prognostic indicators of patients with stage 4 neuroblastoma who were older than 18 months at diagnosis. The medical records of 118 such children who were treated at Shanghai Children's Medical Center, China, from June 1998-December 2013 were reviewed. Event-free survival (EFS) and overall survival (OS) were analyzed by log-rank tests. Of the 118 patients, 14 improving patients did not complete treatment because of parental decisions, and 1 patient died during surgery. Of the 103 patients who completed the comprehensive protocols, 60 (58.3%) achieved very good partial remission (VGPR), 26 (25.2%) achieved partial remission (PR) after four courses of chemotherapy, and 17 (16.5%) progressed during treatment. The response to induction (including VGPR + PR) was 83.5%. After a median follow-up of 105 months (range 36-160 months), the 5- and 10-year OS were 21 and 18%, and the EFS was 19 and 13%, respectively. EFS was significantly better for patients with normal levels of urinary vanillylmandelic acid (VMA) at diagnosis, who had complete resection of the primary tumor, who were minimal residual disease- (MRD-) negative in their bone marrow after four courses of chemotherapy, and who achieved VGPR at the end of treatment (P < 0.05). The prognosis remains poor for patients with stage 4 neuroblastoma who are older than 18 months at diagnosis. Elevated VMA level, incomplete tumor resection, persistent MRD in bone marrow, and poor curative effect are associated with worse prognosis.


Assuntos
Neuroblastoma/mortalidade , Neuroblastoma/patologia , Neuroblastoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , China , Intervalo Livre de Doença , Feminino , Citometria de Fluxo , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Neoplasia Residual/mortalidade , Neoplasia Residual/patologia , Transplante de Células-Tronco de Sangue Periférico , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Ácido Vanilmandélico/urina
8.
World J Pediatr ; 11(4): 326-30, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26454437

RESUMO

BACKGROUND: The clinical management of children with renal tumors including Wilms' tumor, clear cell sarcoma, rhabdoid tumor and other renal tumors in our center was designed according to the National Wilms' Tumor Study Group protocols. METHODS: A total of 142 consecutive patients who had been diagnosed as having renal tumors at Shanghai Children's Medical Center were reviewed retrospectively in the period of December 1998 and September 2012. Diagnosis and treatment were decided by a multidisciplinary team including oncologists, surgeons, pathologists and sub-specialized radiologists. RESULTS: The median age of the patients at the time of diagnosis was 27 months. The tumor stages of the patients were as follows: stage I 24.6%, stage II 23.2%, stage III 32.3%, stage IV 14.1%, and stage V 5.6%. Favorable histology was diagnosed in 80.3%, anaplasia in 4.2%, clear cell sarcoma in 9.8%, rhabdoid tumor in 4.9%, and other renal tumors in 0.7% of the patients. The event-free and overall 5-year survival rates were 80% and 83%, respectively. Tumor relapse and progress was seen in 25 patients (17.6%). The median relapse time was 6 months (range: 2-37 months). Seven relapsing patients were retreated and four of them got second complete remission (three in stage II, one in stage I). CONCLUSION: A multi-disciplinary team work model is feasible in developing countries, and the renal tumors protocols basically from developed countries are safe in developing countries.


Assuntos
Neoplasias Renais/terapia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Terapia Combinada , Países em Desenvolvimento , Diagnóstico por Imagem , Feminino , Humanos , Lactente , Neoplasias Renais/epidemiologia , Neoplasias Renais/patologia , Masculino , Estadiamento de Neoplasias , Equipe de Assistência ao Paciente , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Pediatr Dev Pathol ; 18(3): 245-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25734608

RESUMO

We report a renal tumor detected by prenatal ultrasound and resected at 2 months of age. This 9-cm, solid mass was composed of tubular and papillary structures lined by small, uniform epithelial cells. There was local invasion into renal parenchyma and a tumor deposit in a hilar lymph node. The tumor was immunopositive for WT1, pankeratin, and CD10; focally positive for CK7; and negative for EMA and TFE3. Based on morphology and immunophenotype, the favored diagnosis was metanephric adenoma over Wilms tumor, renal cell carcinoma, and nephrogenic rest. However, metanephric adenoma only occasionally occurs in children and has never been reported prenatally. Alternatively, this tumor might be a congenital Wilms tumor that differentiated completely. Although the nature of the tumor remains unconfirmed, resection appears to have been curative; the patient remains disease-free 18 months following surgery alone.


Assuntos
Neoplasias Renais/congênito , Neoplasias Renais/patologia , Adenoma/congênito , Adenoma/patologia , Adenoma/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Neoplasias Renais/cirurgia , Nefrectomia , Tumor de Wilms/congênito , Tumor de Wilms/patologia , Tumor de Wilms/cirurgia
10.
Biomed Res Int ; 2014: 894341, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25147822

RESUMO

Here we investigated the establishment of multicenter cooperative treatment groups in China, as well as radiotherapy compliance and effectiveness among children with renal tumors. Medical records were reviewed for 316 children with renal tumors diagnosed by a multicenter cooperative group from 14 hospitals in China from 1998 to 2012. Median patient age was 29.5 months (range, 2-173 months old), and male-to-female ratio was 1.4 : 1. After a median follow-up of 22 months (range, 1-177 months), five-year event-free survival rates were 72% overall; 76.1% for favorable histology (251 cases); 59% for unfavorable histology (27 cases); and 91%, 75%, 71%, 53%, and 48.5%, respectively for Stages I, II, III, IV, and V. Following standardized criteria, radiation therapy was indicated for 153 patients, among whom five-year event-free survival was 72.8% for the 95 who received radiation and 24% for the 58 patients who did not. Our results are reasonable but can be further improved and show the feasibility of a multicenter cooperative group model for childhood renal tumor treatment in China. Radiation therapy is important for stage III and IV patients but remains difficult to implement in some parts of China. Government management departments and medical professionals must pay attention to this situation. This clinical trial is registered with ChiCTR-PRCH-14004372.


Assuntos
Neoplasias Renais/patologia , Adolescente , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , China , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Masculino , Estadiamento de Neoplasias/métodos , Resultado do Tratamento
11.
Am J Clin Oncol ; 35(3): 275-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21537148

RESUMO

OBJECTIVE: 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). PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: Persistence of minimal residual disease in BM may work as a chemotherapy response marker and predict the prognosis in advanced NB.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Medula Óssea/diagnóstico , Medula Óssea/patologia , Neoplasia Residual/diagnóstico , Neuroblastoma/terapia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Antígenos CD34/metabolismo , Neoplasias da Medula Óssea/etiologia , Neoplasias da Medula Óssea/mortalidade , Criança , Pré-Escolar , Terapia Combinada , Progressão da Doença , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Neoplasia Residual/etiologia , Neoplasia Residual/mortalidade , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Projetos Piloto , Prognóstico , Taxa de Sobrevida
12.
Chin J Cancer ; 29(12): 1012-7, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21114922

RESUMO

BACKGROUND AND OBJECTIVE: Since the proposal of the tumor stem cell hypothesis, considerable interest has been devoted to the isolation and purification of tumor stem cells. Tumor stem cell enrichment from primary tumor derived cell spheres has been demonstrated in specific, serum-free media. This goal of this study is to establish a method of cultivating floating tumor spheres from neuroblastoma cells and to confirm that neuroblastoma spheres are rich in tumor stem cells. METHODS: Bone marrow aspirates were obtained from pediatric patients diagnosed with stage IV neuroblastoma. Primary tumor cells were isolated and cultivated in serum-free, stem cell-selective medium. Single sphere-forming cells were cultivated under serum-free conditions; their cloning efficiency and monoclonal tumor sphere formation rates were calculated. The expression of stem cell marker genes Oct-4 and Bmi-1 was detected by RT-PCR in sphere-forming cells and parental neurolastoma cells. Sphere-forming cells were injected into the armpit of nude mice with subsequent assessment for tumor growth. Sphere-forming cells were cultivated in differentiation medium containing 5 µmol/L 13-cis retinoic acid; changes in cell morphology were observed. RESULTS: Neuroblastoma cells formed non-adherent neurospheres under serum-free, stem cell-selective conditions after a period of 4 to 6 days. A single cell dissociated from a neurosphere could reform a monoclonal sphere; cloning efficiency and monoclonal sphere formation rates were 55.3% and 26.3%, respectively. RT-PCR results revealed heightened tumor sphere expression of Oct-4 and Bmi-1 as compared with parental tumor cells. Fourteen days after injection of 10(4) sphere-forming cells into nude mice, a neuroblastoma xenograft formed. Treatment of sphere-forming cells with 13-cis retinoic acid induced a gradual differentiation to neuronal cell morphology. CONCLUSIONS: Neuroblastoma derived tumor spheres enrich tumor stem cells and the cultivation of primary neuroblastoma cells in serum-free, stem cell-selective medium is an effective method to dissociate and purify tumor stem cells in vitro.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Neuroblastoma/patologia , Esferoides Celulares/patologia , Animais , Técnicas de Cultura de Células/métodos , Criança , Meios de Cultura Livres de Soro , Humanos , Isotretinoína/farmacologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Neuroblastoma/metabolismo , Proteínas Nucleares/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Complexo Repressor Polycomb 1 , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
World J Pediatr ; 6(1): 43-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20143210

RESUMO

BACKGROUND: Little was known about the therapeutic result of rhabdomyosarcomas (RMSs) and other malignant tumors until the end of the last century in China. Very few prospective clinical research results have been reported. We designed a RS-99 protocol under close cooperation of a multidisciplinary team including surgeons, radiologists, pathologists, and pediatric oncologists at Shanghai Children's Medical Center. This study aimed to improve the prognosis of childhood solid tumors and analyze the results of different tumors with the same protocol, including RMSs, the Ewing sarcoma family of tumors (ESFTs), and ex-cranial germ cell tumors (GCTs). METHODS: Sixty-six patients with malignant solid tumors [RMS (n=30), GCT (n=22), and ESFT (n=14)] were enrolled on the RS-99 protocol from October 1998 to October 2006. They were 34 girls and 32 boys aged 9 to 194 months. The protocol involved surgery, radiotherapy and chemotherapy which included VCP (vincristine, cisdiaminedichloroplatinum, and cyclophosphamide) and IEV (etoposide, vincristine and ifosfamide) for the low-risk group, AVCP (adriamycin, vincristine, cisdiaminedichloroplatinum, and cyclophosphamide) and IEV for the intermediate-risk group and high-risk group. Peripheral blood stem cell transplantation was suggested for the high-risk group. Radiotherapy was only given for RMS and ESFT. Differences in survival between the groups were determined by comparison of entire survival curves and tested by the Kaplan-Meier method and the log-rank tests. RESULTS: The 5-year event-free survival (EFS) for the whole group (RMS, ESFT and GCT) was 60%. The 5-year EFS for children with RMS was 35% (95% CI 16-54), GCT was 79% (95% CI 70-88) and ESFT was 72% (95% CI 58-86). The 5-year EFS showed that the patients with RMS in the retroperitoneum-pelvis did not have a better result than those with tumors in other sites (P=0.604). The histological classification of RMS exerted prognostic influence on the estimated 5-year EFS (P=0.04). Tumor stage and risk group were also contributive to prognosis (P=0.008). For GCT patients, the primary sites of tumors and their histological classification did not influence the therapeutic result (P=0.814). The 5-year EFS was 100% in stage I and II versus 62% in stage III and IV patients (P=0.02). Because of the small number of patients, we did not analyze the prognostic factors for patients with ESFT. No organ failure or functional impairment occurred in the patients enrolled in the RS-99 protocol. One ESFT patient developed a second cancer. CONCLUSIONS: The RS-99 protocol is well tolerated and is reasonable for the 3 different tumors. Risk-based grouping protocol design is needed and the protocol for high risk RMS should be revised.


Assuntos
Neoplasias Ósseas/terapia , Neoplasias Embrionárias de Células Germinativas/terapia , Rabdomiossarcoma/terapia , Sarcoma de Ewing/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Epirubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Ifosfamida/uso terapêutico , Lactente , Masculino , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Transplante de Células-Tronco de Sangue Periférico , Prednisolona/uso terapêutico , Prognóstico , Radioterapia Adjuvante , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/patologia , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/patologia , Tamoxifeno/uso terapêutico , Vincristina/uso terapêutico
14.
Pediatr Blood Cancer ; 49(7): 952-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17514736

RESUMO

OBJECTIVE: To determine whether neuroblastoma (NB) minimal residual disease (MRD) in bone marrow (BM) detected by flow cytometry could predict prognosis and whether tumor cell purging by CD34(+) cell selection prior to transplantation will impact on disease-free survival. METHODS: NB MRD in BM was evaluated by flow cytometry with CD45-FITC-/CD81-PE+/CD56-PECy5+ monoclonal antibodies cocktail. Peripheral blood stem cell (PBSC) was enriched via positive CD34(+) cell selection by magnetic-activated cell separation system (MACS). RESULTS: Eleven of 31 patients with CD45(-)/CD81+/CD56+ cells by flow cytometry at diagnosis became negative after an average of four courses of chemotherapy. All 11 patients remained alive without evidence of disease. Thirteen of the 20 patients with positive MRD relapsed and 1 patient died from disease (mean 25.8 months). There was a significant difference between these two groups. MRD in BM was tested before PBSC transplantation (PBSCT) for 19 NB patients. Fourteen was negative, 4 of them relapsed and 10 patients remained alive without evidence of disease. Another 5 patients with positive MRD, all of them relapsed (mean 17 months after PBSCT) with a significant difference between these two groups. Fourteen of 19 PBSC were purged with CD34(+) selection procedure. Six of 14 relapsed (mean 18.43 months after PBSCT). Five patients did not purge for CD34(+) selection, and 3 of them relapsed with no significant difference between these two groups. CONCLUSIONS: Positive MRD in BM after an average of four courses of chemotherapy and before PBSCT is an unfavorable factor for stage IV NB. CD34(+) selection purging for PBSCT may not improve the prognosis for children with neuroblastoma in advanced stage.


Assuntos
Antígenos CD34/análise , Neoplasias Ósseas/diagnóstico , Citometria de Fluxo , Neoplasia Residual/diagnóstico , Neuroblastoma/diagnóstico , Transplante de Células-Tronco de Sangue Periférico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Neoplasias Ósseas/tratamento farmacológico , Criança , Pré-Escolar , Progressão da Doença , Intervalo Livre de Doença , Feminino , Citometria de Fluxo/métodos , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Neoplasia Residual/tratamento farmacológico , Neuroblastoma/tratamento farmacológico , Prognóstico , Recidiva , Sensibilidade e Especificidade , Resultado do Tratamento
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