While survival has improved for Burkitt lymphoma patients, potential differences in outcome between pediatric and adult patients remain unclear. In both age groups, survival remains poor at relapse. Therefore, we conducted a comparative study in a large pediatric cohort, including 191 cases and 97 samples from adults. WhileTP53andCCND3mutation frequencies are not age related, samples from pediatric patients showed a higher frequency of mutations inID3,DDX3X, ARID1AandSMARCA4, while several genes such asBCL2andYY1AP1are almost exclusively mutated in adult patients. An unbiased analysis reveals a transition of the mutational profile between 25 and 40 years of age. Survival analysis in the pediatric cohort confirms thatTP53mutations are significantly associated with higher incidence of relapse (25 ± 4% versus 6 ± 2%, p-value 0.0002). This identifies a promising molecular marker for relapse incidence in pediatric BL which will be used in future clinical trials.

With the aim of describing the long-term follow-up and to define the prognostic role of the clinical/pathological/molecular characteristics at diagnosis for childhood, adolescent and young adults affected by anaplastic large cell lymphoma (ALCL), we analyzed 420 patients aged up to 22 years homogeneously treated within the international ALCL99 trial. The 10-year progression free survival (PFS) was 70% and overall survival was 90%, rare late relapses occurred but no secondary malignancies were reported. Among clinical/pathological characteristics, only patients presenting a small cell/lymphohistiocytic (SC/LH) pattern were independently associated with risk of failure (hazard ratio = 2.49). Analysis of minimal disseminated disease (MDD), available for 162 patients, showed that both SC/LH pattern (hazard ratio = 2.4) and MDD positivity (hazard ratio = 2.15) were significantly associated with risk of failure in multivariate analysis. Considering MDD and SC/LH results, patients were separated into three biological/pathological (bp) risk groups: a high-risk group (bpHR) including MDD-positive patients with SC/LH pattern; a low-risk group (bpLR) including MDD-negative patients without SC/LH pattern; and an intermediate-risk group (bpIR) including remaining patients. The 10-year PFS was 40%, 75% and 86% for bpHR, bpIR and bpLR, respectively (p < 0.0001). These results should be considered in the design of future ALCL trials to tailor individual treatments.

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations.

Children with refractory or relapsed Burkitt lymphoma have a poor chance to survive. We describe characteristics, outcome, re-induction and transplantation-approaches and evaluate risk factors among children with progression of a Burkitt lymphoma/leukemia included in NHL-BFM studies between 1986 and 2016. Treatment recommendation was re-induction including rituximab from the early 2000s followed by blood stem cell transplantation. The 3-year survival of the 157 children was 18.5{plus minus}3%. Survival significantly improved from 11{plus minus}3% before to 27{plus minus}5% after 2000 (p<.001) allowing for risk factor analyses among the latter 75 patients, of whom 28 had disease progressive during initial therapy. Survival of 14 patients with relapse after initial therapy for low risk disease (R1/R2) was 50{plus minus}13% compared to 21{plus minus}5% for 61 patients progressing after R3/R4-therapy (p<.02). 25 of 28 patients with progression during first-line therapy, 31 of 32 with progression during re-induction, 15 of 16 not reaching a complete remission before transplantation, 9 of 10 treated with rituximab front-line and all 13 patients not receiving rituximab during re-induction died. 46 patients received stem cell transplantation (20 autologous, 26 allogeneic). Survival after a regimen combining Rituximab with continuous-infusion chemotherapy followed by allogeneic transplantation was 67{plus minus}12% compared to 18{plus minus}5% for all other regimen and transplantations (p=.003). Patients with relapsed Burkitt lymphoma/leukemia have a poor chance to survive after current effective front-line therapies. Progression during initial or re-induction chemotherapy and initial high-risk disease are risk-factors in relapse. Time-condensed continuous-infusion re-induction followed by stem cell transplantation forms the basis for testing new drugs.

Pediatric‐type follicular lymphoma (PTFL), pediatric nodal marginal zone lymphoma (pnMZL), and large B‐cell lymphoma (LBCL) with IRF4 rearrangement have been introduced into the current World Health Organization (WHO) classification. They account for 5% to 10% of mature B‐cell lymphomas in children and adolescents. Both PTFL and pnMZL predominantly affect male adolescents and usually present with localized lymphadenopathy in the head and neck region. The cells within the follicles of PTFL typically show high‐grade cytology, IGH monoclonality and lack the t(14;18) chromosomal alteration. In contrast, pnMZL is characterized by progressive transformation of germinal center (PTGC)‐like features and interfollicular proliferation of the cells with expansion of the marginal zones with diffuse areas. Watch and wait after complete resection seems an adequate therapy with chemotherapy restricted to incompletely resected disease. All children with PTFL and pnMZL reported, so far, survived. B‐cell lymphomas presenting in the Waldeyer's ring are characterized by the expression of IRF4/MUM1 and often associated with IRF4 rearrangements. Because of the frequent diffuse component, treatment often follows current protocols for mature B‐NHL. The prognosis is excellent.