Vera Lúcia Lins de Morais

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.

MTR polymorphic variant A2756G and retinoblastoma risk in Brazilian children

Polymorphisms in the genes of folate and methionine metabolism enzymes have been associated with some forms of cancer by affecting DNA synthesis, repair, and methylation.

Carboplatin in the treatment of Ewing sarcoma: Results of the first Brazilian Collaborative Study Group for Ewing Sarcoma Family Tumors—EWING1

Large cooperative group studies have shown the efficacy of risk‐adapted treatment for Ewing sarcoma. However, validation and local adaptation by National cooperative groups is needed. A multicenter protocol to determine the efficacy and safety of a risk‐adapted intensive regimen was developed by the Brazilian cooperative group.

Número de áreas anatômicas envolvidas como preditor de risco no linfoma de Hodgkin em crianças: um estudo retrospectivo

OBJECTIVES To determine if the number of involved anatomic areas can modify the standard risk groups in pediatric Hodgkins 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.

Diagnosing lymphoma in a setting with a high burden of infection: a pediatric case of Epstein-Barr virus-associated aggressive B-cell lymphoma with t(8;14) (q23;q32) and extensive necrosis mimicking tuberculosis

The association of lymphoma with necrotic granuloma can pose diagnostic challenges and delay treatment, especially in settings with a high burden of infection. In these settings, the timely use of cytogenetic and molecular methods is most relevant. Here, we report a case of B-cell lymphoma with t (8;14) in a 5-year-old male child. The lymphoma was associated with necrotic granuloma and was initially misdiagnosed as tuberculosis. Polymerase chain reaction was used to detect clonal lymphoproliferation and to rule out Mycobacterium tuberculosis infection. Tumor cells harbored Epstein-Barr virus and expressed CD20, CD10, BCL6, and Ki67 (30%), leading to the diagnosis of B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

Myeloproliferative syndrome of monosomy 7: a brief report

We report the case of a five-month-old black male infant who had recurrent episodes of respiratory infections and also presented anemia and enlargements of the spleen, liver and lymphnodes. Hematological analysis revealed morphological abnormalities with megaloblastic dyserythropoiesis, while fetal hemoglobin assaying showed normal levels. Conventional and molecular cytogenetic analysis revealed monosomy of chromosome 7. Despite all therapeutic efforts during allogenic bone marrow transplantation, the child died due to generalized infection. The clinical and genetic distinctions between monosomy 7 syndrome and myelodysplastic disorders in childhood are discussed.