Benefits of the intermittent use of 6-mercaptopurine and methotrexate in maintenance treatment for low-risk acute lymphoblastic leukemia in children: randomized trial from the Brazilian Childhood Cooperative Group--protocol ALL-99.

PURPOSE To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MTX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. PATIENTS AND METHODS Between October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n = 544) were randomly allocated to receive either continuous 6-MP/MTX (group 1, n = 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MTX (200 mg/m(2) every 3 weeks; group 2, n = 272). RESULTS The 5-year overall survival (OS) and EFS were 92.5% +/- 1.5% SE and 83.6% +/- 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% +/- 2.2% SE (group 1) and 93.6% +/- 2.1% SE (group 2; P = .28) and EFS 80.9% +/- 3.2% SE (group 1) and 86.5% +/- 2.8% SE (group 2; P = .089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P = .027), while no difference was seen for girls (87.0% v 88.8% SE; P = .78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P = .002), and 772 and 636 for hematologic episodes (P = .005). Deaths on maintenance were: seven (group 1) and one (group 2). CONCLUSION The intermittent use of 6-MP and MTX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.

Number of involved anatomic areas as a risk predictor in pediatric Hodgkin's lymphoma: a retrospective study.

OBJECTIVES: To determine if the number of involved anatomic areas can modify the standard risk groups in pediatric Hodgkin's lymphoma, identifying children who would benefit from a reduction in treatment intensity. METHODS: Retrospective study evaluating age, sex, histology, Ann-Arbor stage, presence of B symptoms, number of involved anatomic areas, risk grouping (favorable vs. unfavorable), and laboratory exams. All patients received doxorubicin-containing chemotherapy. Patients in complete remission for 5 years or longer were evaluated as for late effects. RESULTS: Sixty-nine patients (2-18 years) were included, 68% belonged to the unfavorable risk group. Overall survival and event-free survival were 94 and 87%, respectively. Late effects were screened in 46 cases. Advanced stage and > or = four involved anatomic areas had negative impact on event-free survival, while only the number of involved anatomic areas retained statistical significance when using Cox analysis (hazard ratio = 6.4, 95%CI = 1.08-38.33; p = 0.04). Risk groups were adjusted by number of involved anatomic areas (< four/> or = four involved anatomic areas), with a significant reallocation of patients (p = 0.008). Of the 30 patients with late effects, 21 were in the original unfavorable risk group and 14 (66.6%) could have been reallocated to the favorable risk group based on the number of involved anatomic areas. CONCLUSIONS: If re-stratification had been applied, a considerable number of children would have received less intensive treatment and, consequently, could have had lower chances of late effects. A prospective study could define if adjustment of risk group by number of involved anatomic areas would have any impact on survival rates.

Número de áreas anatômicas envolvidas como preditor de risco no linfoma de Hodgkin em crianças: um estudo retrospectivo / Number of involved anatomic areas as a risk predictor in pediatric Hodgkin's lymphoma: a retrospective study

OBJETIVO: Determinar se o número de áreas anatômicas envolvidas pode modificar os grupos de risco padrão no linfoma de Hodgkin pediátrico, identificando as crianças que poderiam se beneficiar de uma redução da intensidade do tratamento. MÉTODOS: Estudo retrospectivo com avaliação de idade, sexo, histologia, classificação de Ann-Arbor, presença de sintomas B, número de áreas anatômicas envolvidas, grupos de risco (favorável versus desfavorável) e exames laboratoriais. Todos os pacientes receberam quimioterapia com doxorrubicina. Os pacientes em remissão completa por 5 anos ou mais foram avaliados para a detecção de efeitos tardios. RESULTADOS: Sessenta e nove pacientes (2-18 anos) foram incluídos, sendo que 68 por cento pertenciam ao grupo de risco desfavorável. A sobrevida global e a sobrevida livre de eventos foram de 94 e 87 por cento, respectivamente. Os efeitos tardios foram detectados em 46 casos. Estágio avançado e > quatro áreas anatômicas envolvidas tiveram impacto negativo sobre a sobrevida livre de eventos, enquanto que o número de áreas anatômicas envolvidas apresentou significância estatística de acordo com a análise de Cox (razão de risco = 6,4; IC95 por cento = 1,08-38,33; p = 0,04). Os grupos de risco foram ajustados por número de áreas anatômicas envolvidas (< quatro/> quatro áreas anatômicas envolvidas), com uma significativa realocação de pacientes (p = 0,008). Dos 30 pacientes com efeitos tardios, 21 estavam no grupo de risco desfavorável original, e 14 poderiam ter sido realocados para o grupo de risco favorável com base no número de áreas anatômicas envolvidas. CONCLUSÃO: Se uma reestratificação tivesse sido aplicada, um número considerável de crianças teria recebido tratamento de menor intensidade e, consequentemente, poderia ter tido menores chances de apresentar efeitos tardios. Um estudo prospectivo poderia definir se o ajuste de grupos de risco pelo número de áreas anatômicas envolvidas teria algum impacto sobre ...

OBJECTIVE: To determine if the number of involved anatomic areas can modify the standard risk groups in pediatric Hodgkin's lymphoma, identifying children who would benefit from a reduction in treatment intensity. METHODS: Retrospective study evaluating age, sex, histology, Ann-Arbor stage, presence of B symptoms, number of involved anatomic areas, risk grouping (favorable vs. unfavorable), and laboratory exams. All patients received doxorubicin-containing chemotherapy. Patients in complete remission for 5 years or longer were evaluated as for late effects. RESULTS: Sixty-nine patients (2-18 years) were included, 68 percent belonged to the unfavorable risk group. Overall survival and event-free survival were 94 and 87 percent, respectively. Late effects were screened in 46 cases. Advanced stage and > four involved anatomic areas had negative impact on event-free survival, while only the number of involved anatomic areas retained statistical significance when using Cox analysis (hazard ratio = 6.4, 95 percentCI = 1.08-38.33; p = 0.04). Risk groups were adjusted by number of involved anatomic areas (< four/> four involved anatomic areas), with a significant reallocation of patients (p = 0.008). Of the 30 patients with late effects, 21 were in the original unfavorable risk group and 14 (66.6 percent) could have been reallocated to the favorable risk group based on the number of involved anatomic areas. CONCLUSION: If re-stratification had been applied, a considerable number of children would have received less intensive treatment and, consequently, could have had lower chances of late effects. A prospective study could define if adjustment of risk group by number of involved anatomic areas would have any impact on survival rates.

Neuroblastoma intrarenal mimetizando tumor de Wilms / Intrarenal neuroblatoma mimics Wilms' tumor

No presente trabalho, os autores relatam o caso de uma criança com neuroblastoma intrarenal, que foi, inicialmente,diagnosticado como tumor de Wilms. Pré-escolar, sexo feminino, com um ano e três meses, apresentava uma tumoração endurecida que ocupava o hipocôndrio esquerdo e se estendia até a região do mesogástrio, acompanhada de febre e palidez. O ultra-som do abdome total revelou massa intrarenal. A biópsia por agulha fina, em vários pontos de acesso tumoral, revelou um tumor de Wilms. Entretanto, não foi possível naquele momento realizar a imunohistoquímica (IHQ), face à escassez de material. Diante da gravidade da paciente, foi iniciado o protocolo SIOP por quatro semanas. Como não houve resposta clínica, foi indicada uma laparotomia exploradora, com ressecção parcial do tumor, sendo também, nesse momento, realizada punção aspirativa de medula óssea (MO). O exame histopatológico revelou neoplasia maligna de pequenas células mal diferenciadas. A IHQ foi negativa para WT-1 e positiva para NB-84, cromogranina e sinaptofisina. A biologia molecular revelou amplificação de N-myc. O mielograma identificou infiltração medular por pequenas células redondas. O neuroblastoma intrarenal é um tumor raro que se assemelha clínica e radiologicamente ao tumor de Wilms. Esse trabalho procura enfatizar a importância do emprego de análises imunohistoquímica e moleculares para o diagnóstico do neuroblastoma intrarenal.

This work reports the case history of a child with intrarenal neuroblastoma, initially diagnosed as Wilms' tumor.The patient, a one year and three months old girl, presented a hard abdominal mass on the left flank that extended to the mesogastric region, plus fever and paleness. The ultrasound of the entire abdomen revealed an intrarenal mass. Biopsy with fine needle in many points of the tumor revealed Wilms' tumor. The scarcety of the material, however, made immunohistoquemistry impossible at that moment. Because of the child's severe condition the SIOP protocol was started. As no clinical response was observed, an exploratory laparatomy was indicated with partial resection of the tumor and bone marrow aspiration (MO). The histopathologic study revealed a malignant neoplasia of small cells, poorly differentiated. IHQ was negative for WT-1 and positive for NB-84, synaptofisin, cromogranine. N-myc amplification was observed by molecular biology. The bone marrow aspiration identified matastatic small round cells infiltration. Intrarenal neuroblastoma is a rare entity that clinically and radiographicallyresembles Wilms' tumor. The objective of this case report is to show the importance of immunohistochemical andmolecular analysis in the diagnosis of intrarenal neuroblastoma.

t(4; 11) (q21; q23) in acute myeloid leukemia-M0 following treatment [EW92 Protocol] for Ewing's sarcoma / Leucemia mielóide aguda-M0 com t(4;11) (q21;q23) após tratamento para sarcoma de Ewing com o protocolo EW92

Nós descrevemos o caso clínico de uma criança do sexo feminino, com 7 anos de idade, portadora de sarcoma de Ewing, que evoluiu com leucemia aguda mielóide pouco diferenciada (LMA-M0) após vinte meses de tratamento utilizando o protocolo EW92. Ela recebeu uma dose total de 1.500 mg de etoposídio, irradiação tumoral na dose total de 35G, e fator de estimulação de colônia granulocítica (G-CSF) conforme programação do protocolo terapêutico. Os exames laboratoriais, por ocasião do diagnóstico da segunda malignidade, mostraram células blásticas imaturas caracterizadas pela expressão de CD34+/CD33-/aMPO+ e a translocação t(4;11) (q 21;q23). A exclusão do G-CSF nos esquemas terapêuticos que associam etoposídio e irradiação tumoral se justifica devido a esta séria complicação no tratamento do sarcoma de Ewing.