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Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse

Outcome among high-risk pediatric patients with ALL after hematopoietic stem-cell transplantation was not affected by donor type. Standardized myeloablative conditioning produced a low incidence of treatment-related mortality and effective control of leukemia.

Adding vinblastine during induction and as maintenance for a total treatment duration of 1 year significantly delayed the occurrence of relapses but did not reduce the risk of failure.

BackgroundPediatric follicular lymphoma has recently been recognized as a novel variant of follicular lymphoma in the World Health Organization classification of lymphomas. Given the rarity of the disease, histopathological and genetic data on this type of lymphoma are still scarce. Design and MethodsWe analyzed 25 cases of pediatric follicular lymphoma (patients aged ≤18 years) by morphology, immunohistochemistry and interphase fluorescence in situ hybridization. All patients analyzed were treated within Non-Hodgkin's Lymphoma -Berlin-FrankfurtMünster (NHL-BFM) multicenter trials, and the cohort was representative of the German population. ResultsThe genetic hallmark of adult follicular lymphoma, t(14;18)(q32;q21), was not detectable in any of the pediatric cases, although BCL2 protein was expressed in 55% of the latter cases. No correlation was found between BCL2 protein expression and outcome. Chromosomal breaks in the immunoglobulin heavy chain gene (IGH) and the BCL6 locus were detected in 5 of 17 and 1 of 18 cases, respectively. Patients with pediatric follicular lymphoma had long event-free survival and, in contrast to adult follicular lymphoma, the clinical course was not dominated by relapses. A simultaneous diffuse large B-cell lymphoma was frequently detected at initial diagnosis in children but did not indicate an aggressive clinical course. ConclusionsOur data suggest that pediatric follicular lymphoma is a disease that differs from its adult counterpart both genetically and clinically.Key words: pediatric follicular lymphoma, childhood lymphoma, pediatric diffuse large B-cell lymphoma, t(14;18). NonHodgkin's Lymphoma -Berlin-Frankfurt-Münster (NHL-BFM) multicenter trials. Haematologica. 2010; 95:253-259. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Oschlies I, Salaverria I, Mahn F, Meinhardt A, Zimmermann M, Woessmann W, Burkhardt B, Gesk S, Krams M, Reiter A, Siebert R, and Klapper W. Pediatric follicular lymphoma -a clinico-pathological study of a population-based series of patients treated within thePediatric follicular lymphoma -a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin's Lymphoma -Berlin-FrankfurtMünster (NHL-BFM) multicenter trials

For CNS-negative patients with stage III or IV LBL and sufficient response to induction therapy, treatment without PCRT may be noninferior to treatment including PCRT.

SummaryHaemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome. Haemophagocytic lymphohistiocytosis was considered triggered by the malignancy (M-HLH) in 21 patients, most of whom had T-(n = 12) or B-cell neoplasms (n = 7), with Epstein-Barr virus as a co-trigger in five patients. In eight patients, HLH occurred during chemotherapy (Ch-HLH) for malignancy, mainly acute leukaemias (n = 7); an infectious trigger was found in seven. In Mand Ch-HLH, median overall survival was 1Á2 and 0Á9 years, and the 6 month survival rates were 67% and 63%, respectively. Seven of 11 deceased M-HLH patients exhibited active malignancy and HLH at the time of death, while only two out of five deceased Ch-HLH patients had evidence of active HLH. To overcome HLH, malignancy-and HLH-directed treatments were administered in the M-HLH cohort; however, it was not possible to determine superiority of one approach over the other. For Ch-HLH, treatment ranged from postponement of chemotherapy to the use of etoposide-containing regimens.

Diffuse large B-cell lymphoma is the most frequent type of B-cell lymphoma in adult patients but also occurs in children. Patients are currently assigned to therapy regimens based on arbitrarily chosen age limits only (eg, 18 or 60 years) and not biologically justified limits. A total of 364 diffuse large B-cell lymphomas and related mature aggressive B-cell lymphomas other than Burkitt lymphoma from all age groups were analyzed by comprehensive molecular profiling. The probability of several biologic features previously reported to be associated with poor prognosis in diffuse large B-cell lymphoma, such as ABC subtype, BCL2 expression, or cytogenetic complexity, increases with age at diagnosis. Similarly, various genetic features, such as IRF4 translocations, gains in 1q21, 18q21, 7p22, and 7q21, as well as changes in 3q27, including gains and translocations affecting the BCL6 locus, are significantly associated with patient age, but no cut-offs between age groups could be defined. If age was incorporated in multivariate analyses, genetic complexity lost its prognostic significance, whereas the prognostic impact of ABC subtype and age were additive. Our data indicate that aging is a major determinant of lymphoma biology. They challenge current concepts regarding both prognostic biomarkers and treatment stratification based on strict age cut-offs. (Blood. 2012;119(8): 1882-1887)