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Concerns about long-term methotrexate (MTX) neurotoxicity in the 1990s led to modifications in intrathecal (IT) therapy, leucovorin rescue, and frequency of systemic MTX administration in children with acute lymphoblastic leukemia. In this study, neurocognitive outcomes and neuroradiologic evidence of leukoencephalopathy were compared in children treated with intense central nervous system (CNS)-directed therapy (P9605) versus those receiving fewer CNS-directed treatment days during intensive consolidation (P9201). A total of 66 children from 16 Pediatric Oncology Group institutions with "standard-risk" acute lymphoblastic leukemia, 1.00 to 9.99 years at diagnosis, without evidence of CNS leukemia at diagnosis were enrolled on ACCL0131: 28 from P9201 and 38 from P9605. Magnetic resonance imaging scans and standard neuropsychological tests were performed ≥2.6 years after the end of treatment. Significantly more P9605 patients developed leukoencephalopathy compared with P9201 patients (68%, 95% confidence interval 49%-83% vs. 22%, 95% confidence interval 5%-44%; P=0.001) identified as late as 7.7 years after the end of treatment. Overall, 40% of patients scored <85 on either Verbal or Performance IQ. Children on both studies had significant attention problems, but P9605 children scored below average on more neurocognitive measures than those treated on P9201 (82%, 14/17 measures vs. 24%, 4/17 measures). This supports ongoing concerns about intensive MTX exposure as a major contributor to CNS late effects.

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BACKGROUND: Ewing sarcoma (ES) is a rare, primary malignancy of bone that occurs in childhood and early adolescence. Improved methods of diagnosis and treatment have dramatically increased survival over the last 20 years. Treatment mainstays are chemotherapy and surgical tumor resection. ES usually occurs in long bones of the axial skeleton; however, it may rarely arise in facial structures, particularly the mandible. In these cases, resection presents a challenging postsurgical reconstruction. METHODS AND RESULTS: We present the clinical findings and management of a case of ES that developed in the left mandibular condyle of a 15-year-old female. Chemotherapy and segmental mandibulectomy were used to achieve local control. An innovative temporomandibular joint reconstruction was successfully accomplished using a microvascular fibular free flap and conchal cartilage graft. CONCLUSION: Multidisciplinary management in diagnosis, treatment, and restoration of function produced an optimal result that eliminated disease and preserved aesthetics and quality of life.

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Infectious disease histories were evaluated in a population-based case-control study of childhood acute lymphoblastic leukaemia (ALL) as it has been hypothesised that delays in early infections are associated with an increased risk of disease. Allergy histories were also assessed as part of a broader evaluation of the role of immune factors in ALL. Cases (n = 255) were diagnosed between 1980 and 1991 at one of four referral centres in a 31-county area of New York State; controls (n = 760) were a random sample of live births from the same region, frequency matched to cases by sex, race and birth year. Data were collected by mailed questionnaire, completed by case and control parents in 1995. Allergy and infectious histories before the age at leukaemia diagnosis for cases and an equivalent age for controls were evaluated. The adjusted odds ratio and 95% confidence interval [CI] associated with a positive history of any allergy was 0.58 [95% CI 0.38, 0.88] compared with a negative allergy history. The occurrence of several common childhood illnesses before 25 months of age and ALL were assessed, with both weak positive and weak inverse associations observed. Overall, these analyses provide little support for the hypothesis that infection delay in early life is associated with an increased risk of ALL. Children with positive allergy histories reported significantly more infections than those with negative histories; however, effect modification of the infection-ALL associations by child allergy history was not observed. Nonetheless, these observations suggest the importance of assessing both allergy and infectious histories and their possible interactions when evaluating the association between these immune factors and childhood ALL.

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The purpose of this study was to evaluate fluorescence in situ hybridization abnormalities of the 2p23 anaplastic lymphoma kinase (ALK) gene loci in lymphomas with anaplastic morphology. We studied 24 anaplastic large cell lymphomas (ALCL) classified by World Health Organization criteria [17 primary nodal/systemic (10 ALK+, 7 ALK-), seven primary cutaneous], and 17 additional non-Hodgkin's lymphomas [one ALK+ B-lineage lymphoma, 14 ALK- diffuse large B-cell lymphomas (seven anaplastic variants, five nonanaplastic, two secondary CD30+), two follicular lymphomas]. ALK- lymphomas with anaplastic morphology showed extra nonrearranged anaplastic lymphoma kinase gene loci (P=0.004) due to trisomy 2 irrespective of the following factors: B or T/null phenotype (P=0.315), diagnostic categories of systemic or cutaneous ALCL or the above-mentioned B-cell lymphomas (P=0.131), and CD30 positivity by immunohistochemistry (P=1.000). Trisomy 2 was absent in all ALK+ lymphomas (P=0.009), which showed rearranged ALK gene loci (P<0.001). Whether trisomy 2 is a primary or secondary event that leads to ALK- lymphomas cannot be determined from this study. Its presence in secondary B-cell lymphomas suggests that trisomy 2 may be a secondary cytogenetic aberration in lymphomas in general. Further investigation of this finding is necessary to further our understanding of the heterogeneous group of ALK- lymphomas.

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We describe 15 patients (9 children) with precursor B-cell (pB) acute lymphoblastic leukemia (ALL) with surface immunoglobulin (sIg) light chain restriction revealed by flow cytometric immunophenotyping (FCI). The same sIg+ immunophenotype was present at diagnosis and in 3 relapses in 1 patient. In 15 patients, blasts were CD19+ CD10+ (bright coexpression) in 14, CD34+ in 12, surface kappa+ in 12, surface lambda+ in 3; in 8 of 8, terminal deoxyribonucleotidyl transferase (TdT)+; and in 4, surface IgD+ in 2 and surface IgM+ in 1. The 3 CD34- cases included 1 TdT+ case, 1 with t(1;19)(q23;p13), and 1 infant with 70% marrow blasts. One adult had CD10- CD19+ CD20- CD22+ CD34+ TdT+ sIg+ blasts with t(2;11)(p21;q23). Blasts were L1 or L2 in all cases (French-American-British classification). Karyotypic analysis in 12 of 12 analyzable cases was negative for 8q24 (myc) translocation. Karyotypic abnormalities, confirmed by fluorescence in situ hybridization in 6 cases, included hyperdiploidy, t(1;19)(q23;p13), t(12;21)(p13;q22), t(9;22)(q34;q11), t(2;11)(p21;q23), and trisomy 12. The sIg light chain restriction in pB ALL might be present in neoplasms arising from the early, intermediate, and late stages of precursor B-cell maturation; sIg light chain restriction revealed by FCI does not necessarily indicate a mature B-cell phenotype, further emphasizing the importance of a multidisciplinary approach to diagnosing B-lymphoid neoplasms.

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