RESUMO
BACKGROUND: Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients were randomized to receive single or double reinduction courses. The patients enrolled before 2009 received CrRT, while those enrolled later did not. The Kaplan-Meier method was used to estimate survival rates and the difference between two groups was compared by the two-sided log-rank test. RESULTS: In 1,366 eligible patients, the 5-year overall survival (OS) was 81.6 ± 1.1% (standard error) and 5-year event-free survival (EFS) was 74.3 ± 1.2%. In SR patients, the 5-year OS for one and two reinduction courses was 91.6 ± 2.1% and 93.7 ± 1.8%, respectively, and the 5-year EFS was 85.2 ± 2.7% and 89.8 ± 2.3%, respectively. There were no significant differences in survival between these two groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4 and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no significant difference in CNS relapse or survival between the era with or without CrRT. CONCLUSIONS: For SR patients, one-course reinduction was adequate. Triple intrathecal therapy alone successfully prevented CNS relapse.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Irradiação Craniana , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Discontinuation of E. coli l-asparaginase in patients with acute lymphoblastic leukemia (ALL) is unavoidable upon severe allergic reaction. We sought to examine outcomes following E. coli l-asparaginase discontinuation due to severe allergic reactions. PROCEDURE: We evaluated the outcome of children enrolled in Taiwan Pediatric Oncology Group-2002-ALL protocol between 2002 and 2012, who had E. coli l-asparaginase discontinued due to severe allergic reactions, and compared the outcomes of those who continued with Erwinia l-asparaginase (Erwinase) with those who did not. RESULTS: Among 700 patients enrolled in this study, 33 patients had E. coli l-asparaginase treatment discontinued due to severe allergic reactions. Five-year overall survival did not differ significantly among the 648 patients without discontinuation (81 ± 1.6%, mean ± SE), compared to 17 patients with allergic reactions and treated with Erwinase (88 ± 7.8%) and 16 patients with allergic reactions but not treated with Erwinase (87 ± 8.6%). Among 16 patients who did not receive Erwinase, all 10 who received ≥50% of the scheduled doses of E. coli l-asparaginase before discontinuation survived without events. CONCLUSIONS: Erwinase treatment may not be needed for some ALL patients with severe allergy to E. coli l-asparaginase if ≥50% of prescribed doses were received and/or therapy is augmented with other agents.
Assuntos
Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Hipersensibilidade a Drogas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Criança , Pré-Escolar , Intervalo Livre de Doença , Escherichia coli , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidadeRESUMO
PURPOSE: To identify the prognostic factors and evaluate the impact of chemotherapy regimens on the outcomes of pediatric osteosarcoma of the extremities. METHODS: Patients younger than 18 years and diagnosed with high-grade osteosarcoma of the extremities during the period between January 2004 and December 2011 were included for retrospective analysis. Demographic characteristics and tumor features were compared between nonmetastatic and metastatic patients. Univariate analyses of overall survival (OS) and progression-free survival (PFS) were performed to evaluate the efficacy of various chemotherapy regimens. RESULTS: A total of 74 patients (58 with nonmetastatic and 16 with metastatic disease) were enrolled and treated with three protocols consisting of various cycles of high-dose methotrexate, adriamycin (doxorubicin), cisplatin, and high-dose ifosfamide (MACI regimens) during the 8-year study period. Presence of metastasis was inversely correlated with OS and PFS. Alkaline phosphatase levels at diagnosis and histologic response to preoperative chemotherapy were correlated with OS. Tumor size was correlated with PFS. The 5-year OS and PFS were 77 and 70 % for all patients, and 90.4 and 83.3 % for those with nonmetastatic osteosarcoma; and the rates were both 25 % in those with metastatic osteosarcoma. The chemotherapy regimens increased good response rates by 30 % and survival rates by 20 % compared to the outcomes in patients treated before 2004. CONCLUSIONS: Poor prognostic factors for osteosarcoma in pediatric patients were identified under homogeneous surgical and chemotherapy schemes. The four-drug regimens consisting of MACI contributed to the remarkably increased good response rates and consequent improvement in the survival rates.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/mortalidade , Extremidades/patologia , Neoplasias Pulmonares/mortalidade , Recidiva Local de Neoplasia/mortalidade , Osteossarcoma/mortalidade , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Metotrexato/administração & dosagem , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , TaiwanRESUMO
BACKGROUND: Both ETV6-RUNX1 (TEL-AML1) fusion and hyperdiploidy (>50 chromosomes) in transformed lymphoblasts are favorable genetic features in childhood acute lymphoblastic leukemia (ALL). PROCEDURE: Among 433 Taiwanese children with ALL diagnosed at our hospitals between 1997 and 2007, the ETV6-RUNX1 fusion was found in 15.8%, and hyperdiploidy (>50 chromosomes) in 14.1% of the patients. These frequencies were lower than those reported in the West, leading us to conduct a meta-analysis of ETV6-RUNX1 fusion and hyperdiploidy frequencies in childhood ALL based on published reports. RESULTS: The frequency of ETV6-RUNX1 fusion in the Far East (Japan, Korea, China, Hong Kong, Chinese in Singapore, and Taiwan) was 13.4% (177/1,321, range: 9-23%, median 13%), significantly lower than the 22.8% (1,664/7,291, range: 19-26%, median 23%) in the West (West Europe and the United States) (P < 0.001, odds ratio = 2.0, 95% CI: 1.7-2.4). Similarly, the frequency of hyperdiploidy in Japan and Taiwan was 14.3% (333/2,334, range: 12-20%, median 16%), significantly lower than the 25.2% in the West (5,173/20,510, range: 18-34%, median 23.5%; P < 0.001, odds ratio = 2.0, 95% CI: 1.8-2.3). CONCLUSIONS: This meta-analysis demonstrates lower frequencies of ETV6-RUNX1 fusion and hyperdiploidy among leukemia patients in the Far East compared with the West. The integral relationship of these genetic features with a favorable outcome in childhood ALL warrants further study of potentially important epidemiologic factors, including placental exposure to leukemogenic agents, and host pharmacogenetics.
Assuntos
Diploide , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Povo Asiático/genética , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core , Intervalo Livre de Doença , Europa (Continente) , Ásia Oriental , Humanos , Lactente , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Taxa de Sobrevida , Estados Unidos , População Branca/genéticaRESUMO
Improved treatment of childhood acute lymphoblastic leukemia (ALL) depends on the identification of new molecular markers that are able to predict treatment response and clinical outcome. The development of impaired apoptosis in leukemic cells is one factor that may influence their response to treatment. We investigated the expression of three apoptosis related genes, BCL2L13, CASP8AP2, and Livin, as well as their prognostic significance, in a retrospective study of 90 pediatric ALL patients diagnosed between 1996 and 2007 in Taiwan. Univariant analysis revealed that high expression of BCL2L13 was associated with inferior event-free survival and overall survival (p<0.001 and 0.005, respectively). Multivariate analysis for EFS and OS demonstrated that high expression of BCL2L13 was an independent prognostic factor for childhood ALL in this ethnic group.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Apoptose/genética , Proteínas de Ligação ao Cálcio/genética , Proteínas Inibidoras de Apoptose/genética , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVES: This retrospective study evaluates the role of pharmacogenomic determinants in the treatment of childhood acute lymphoblastic leukemia (ALL) in the Taiwanese population. METHODS: A total of 105 childhood ALL patients received combined chemotherapy of different intensities based on risk-directed Taiwan Pediatric Oncology Group (TPOG)-ALL-93 protocols. Seventeen genetic polymorphisms in 13 pharmacogenomic targets were analyzed by PCR-based restriction fragment length polymorphism (RFLP) and sequence-specific oligonucleotide (SSO) probe hybridization. Pharmacogenomic polymorphisms were correlated with event-free survival (EFS) of patients, with confounding effects adjusted by multivariate regression. RESULTS: Three polymorphic alleles in the multi-drug resistance 1 (MDR1) ABCB1 gene, and homozygotic MDR1 2677GG, 3435CC, and 2677G-3435C genotypes were highly associated with a significant reduction in EFS in those patients treated by the standard risk (SR) protocol (TPOG-ALL-93-SR). The hazard ratios were 6.8 (p = 0.01), 21.7 (p = 0.009), and 6.8 (p = 0.01), respectively. CONCLUSIONS: Independent pharmacogenomic determinants associated with treatment outcome were identified in subsets of Taiwanese ALL patients.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistência a Medicamentos/genética , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Povo Asiático/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Farmacogenética , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , TaiwanRESUMO
Cancer occurring in infants often has clinical and biological properties that are different from those of the same histologic type of cancer occurring in older children. The histologic distribution of cancers in infants and that in older children are also different. We collected infant cases diagnosed as having cancer from the database of the Cancer Registry in our Medical Center between 1995 and 2004. One hundred and twenty infants (66 males and 54 females), including 17 neonates, were diagnosed with cancer over this 10-year period. The top five cancer subtypes were: leukemia in 34 infants (28.3%), retinoblastoma in 19 (15.8%), neuroblastoma in 16 (13.3%), germ cell tumor in 15 (12.5%), and brain tumor in 14 (11.7%). The overall disease-free survival rate was 54. 2% (65/120) with a median follow-up duration of 7.6 years for the survivors. From the cancer registry in our hospital during the same period, 1995-2004, infant cases accounted for 9.5% of the total 1,269 children with cancer diagnosed at the age younger than 15 years. The percent distribution of the major types of cancer was different in the infant and the childhood group. According to the Taiwan Pediatric Oncology Group's data analysis, the infant cancer incidence rate in Taiwan is 207.6 per million infants for years 1995-2004. Our study confirmed that the prognosis is very poor for infant leukemia and rhabdoid tumor, while that is good for embryonal tumors and germ cell tumors occurring in the infancy.
Assuntos
Neoplasias/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Neoplasias/mortalidade , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Tumor Rabdoide/epidemiologiaRESUMO
Cancer occurring in infants often has clinical and biological properties that are different from those of the same histologic type of cancer occurring in older children. The histologic distribution of cancers in infants and that in older children are also different. The aim of this study was to find these differences between infants and older children, and to compare the percent distribution of infant cancer subtypes with that reported by other countries. The authors collected infant cases diagnosed as having cancer from the database of the Cancer Registry in our Medical Center between 1995 and 2001. Subjects were selected subjects from inpatient logs, and their medical records were reviewed. Eighty-two infants (40 males and 42 females), including 12 neonates, were diagnosed with cancer over this 7-year period. Acute leukemia was diagnosed in 21 infants (25.6%; acute myeloid leukemia in 12, and acute lymphoblastic leukemia in 9), retinoblastoma in 14 (17.1%), neuroblastoma in 12 (14.6%), brain tumor in 9 (11.0%), germ cell tumor in 8 (9.8%), renal cancer in 8 (Wilms tumor 3, mesoblastic nephroma 1, renal sarcoma 1, rhabdoid tumor 3), hepatoblastoma in 5 (6.1%), and soft tissue sarcoma in 5 (rhabdomyosarcoma 1, fibrosarcoma 3, other sarcoma 1). The overall disease-free survival rate was 61.0% (50/82) with a median follow-up duration of 6.8 years for the survivors. The 4 most common types of cancer occurring in infants are the same in the present series and in most larger childhood cancer series reported by other countries; but rank differently. In this study there were more infants with acute leukemia and retinoblastoma, and less with neuroblastoma. The prognosis is poor for infant leukemia and rhabdoid tumor, while it is good for embryonal tumors and germ cell tumors occurring in infancy.
Assuntos
Bases de Dados Factuais , Neoplasias/epidemiologia , Neoplasias/mortalidade , Sistema de Registros , Feminino , Humanos , Incidência , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND AND PURPOSE: Taiwan Pediatric Oncology Group (TPOG)-W-91 is the first multi-institutional Wilms' tumor study for children in Taiwan. This clinical trial used a multidisciplinary approach, based on and similar to the National Wilms' Tumor Study 4. The study was conducted to evaluate the epidemiological characteristics and analyze the outcome of Wilms' tumor patients treated with this protocol. METHODS: Ninety eight children with Wilms' tumor (WT) were analyzed for distributions of age, gender, associated congenital anomalies, tumor sites, histology, tumor weights, and clinical stages. Patients received individualized multimodality treatment based upon the histology of the tumor and clinicopathologic stage. The treatment included surgery, radiotherapy and 2-, 3-, and 4-agent active chemotherapeutic agents. Seventy patients were eligible for analysis of treatment outcome. The endpoints were progression-free and overall survival (PFS, OS). Patients were divided into various subgroups according to the chemotherapy regimen used, tumor stage, age at diagnosis, gender, and tumor weight. The prognostic factors were evaluated and the survival rates of various clinical subgroups were compared using log-rank test. RESULTS: The average annual incidence rate of WT was 2.9 per million children under 15 years of age. The M/F ratio was 1.04. The mean age at diagnosis was 3.7 years. All bilateral tumors occurred in females. Congenital anomalies were present in 17.3% of patients. Anaplastic histology was found in 6 of 98 cases (6.1%). The stage distribution was: I, 43.2%; II, 19.3%; III, 23.9%; IV, 6.8%; and V, 6.8%. The median follow-up time was 89.1 months (range, 1.8 to 128.1 months). The 5-year PFS rate was 0.7841 (SE, 0.0494; 53 of 70 patients) and the 5-year OS rate was 0.886 (SE, 0.038; 63 of 70 patients). Gender was found to be the only significant prognostic variable. CONCLUSIONS: This study evaluated the epidemiological characteristics, clinical features, multimodality therapy regimens, and treatment outcome of WT in Taiwan. Data obtained from this study may lead to further improvement in the prognosis of pediatric malignant solid tumor.
Assuntos
Neoplasias Renais/terapia , Tumor de Wilms/terapia , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Neoplasias Renais/epidemiologia , Masculino , Modelos de Riscos Proporcionais , Análise de Sobrevida , Taiwan/epidemiologia , Resultado do Tratamento , Tumor de Wilms/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: The superiority of changing postoperative chemotherapy of osteosarcoma based on histological response of the primary tumor over non-tailored chemotherapy has not been confirmed. This multicenter study evaluated the effectiveness of an intensive unstratified chemotherapy regimen in Taiwanese children with osteosarcoma. METHODS: Fifty patients younger than 18 years of age with previously untreated non-metastatic osteosarcoma of the extremities were enrolled. Patients were treated with pre- and postoperative chemotherapy, and surgery. Definitive surgery was scheduled in week 7 and postoperative chemotherapy was uniform without stratification regardless of histologic response. RESULTS: Chemotherapy toxicities were considerable, but manageable. Treatment delay and decreased dose-intensity were common. There was one treatment-related mortality. Forty three patients (86%) received limb salvage surgery and 14 patients (33%) had a good histologic response to preoperative chemotherapy. With a median follow-up of 47.1 months, the 7-year event-free and overall survival rates were 51.6% and 67.6%, respectively. CONCLUSIONS: This was the first multicenter study on the treatment of osteosarcoma from Taiwan. The results suggest that a non-tailored regimen may serve as an alternative treatment strategy in the management of osteosarcoma, particularly when histologic assessment of the tumor response is not available.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Extremidades , Osteossarcoma/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Estatísticas não Paramétricas , Análise de Sobrevida , Taiwan , Resultado do TratamentoRESUMO
From 1995-1999, a nation-wide study of Langerhans cell histiocytosis (LCH) in children less than 15 years old was conducted by the Taiwan Pediatric Oncology Group. The demographic and clinical data of 55 cases were analyzed. Thirty-two cases presented from the beginning of 1997 to the end of 1998, when the most severe El Niño in the century occurred. The incidence was higher than expected during this El Niño period (32 cases versus 22 cases, p = 0.003). During 1997-98, most LCH was diagnosed in summer (n = 15), autumn (n = 8), and winter (n = 8) but rarely in spring (n = 1); coincidentally, rainfall was least in winter but peaked in summer. During 1997-98, the most significant increase occurred in the polyostotic LCH subcategory (p = 0.017), with younger ages at diagnosis (p = 0.039). The incidence of LCH cytopenia, fever, and diseases of the skin, liver, spleen or other organs did not differ significantly. Local treatment modality, disseminated diseases and diagnosis during the El Niño of 1997-98 were independent risk factors predicting the recurrence or progression of LCH. Our findings suggest that particular infections or other environmental factors associated with El Niño might be related to the etiology of childhood LCH.
Assuntos
Clima , Histiocitose de Células de Langerhans/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Histiocitose de Células de Langerhans/etiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estações do Ano , Taiwan/epidemiologia , Fatores de TempoRESUMO
BACKGROUND: Recently, an internal tandem duplication of the FLT3 gene (FLT3/ITD) was found in approximately 20% of adult acute myeloid leukemia (AML) cases and associated with a poor outcome. However, there are few studies on FLT3/ITD in childhood AML, and the clinical significance of FLT3/ITD is thus unclear. METHODS: FLT3/ITD was analyzed in 80 children with de novo AML. The genomic DNA polymerase chain reaction (PCR) assay was performed to identify FLT3/ITD. Genescan analysis to determine the allelic distribution was then performed for those PCR products with aberrant bands. Direct sequencing of PCR products was also carried out in each sample with FLT3/ITD. RESULTS: The incidence of FLT3/ITD was 11.3% (9 out of 80 patients) in AML, with 25% (3 out of 12 patients) in acute promyelocytic leukemia (APL) and 8.8% (6 out of 68 patients) in non-M3 AML. The size of duplicated fragments varied from 21 base pairs (bp) to 75 bp, and the mutant to wild type ratio of FLT3 ranged from 0.28 to 16.60 in the nine patients with FLT3/ITD. The incidence of FLT3/ITD in childhood AML in patients > 10 years of age was 24%, compared to 5% of those patients Assuntos
Leucemia Mieloide Aguda/genética
, Mutação
, Proteínas Proto-Oncogênicas/genética
, Receptores Proteína Tirosina Quinases/genética
, Sequências de Repetição em Tandem
, Adolescente
, Criança
, Feminino
, Humanos
, Masculino
, Prognóstico
, Tirosina Quinase 3 Semelhante a fms
RESUMO
BACKGROUND: The classification of B-lineage acute lymphoblastic leukemia (ALL) by specific chromosomal translocations may have prognostic implications. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay is a useful tool for the detection of fusion transcript resulting from specific chromosomal translocation of the leukemic cells. In general, fusion transcripts are determined individually, a process which is labor intensive in order to detect all major fusion transcripts. PROCEDURE: We use a multiplex RT-PCR assay to detect both the CML- and ALL-type BCR-ABL transcripts of the t(9;22), all described variants of the E2A-PBX1 transcripts of t(1;19), the MLL-AF4 transcripts of t(4;11), and all described variants of TEL-AML1 (also termed ETV6-CBFA2) of the cryptic t(12;21) in 165 leukemic samples at diagnosis. RESULTS: The study yielded a completely concordant result with those obtained by the individual RT-PCR assay. In this cohort of Taiwan children, the relative frequencies of the four translocations of B-lineage ALL were as following: 6% with ALL-type t(9;22)/BCR-ABL, 7% t(1;19)/E2A-PBX1, 3% t(4;11)/MLL-AF4, and 18% t(12;21)/TEL-AML1, comparable to those in the Western countries. CONCLUSION: Multiplex RT-PCR assay is an efficient, sensitive, accurate, and cost-effective diagnostic tool, which will likely improve our ability in accurately and rapidly risk-stratifying children with ALL.