The study findings support the hypothesis that maternal folic acid supplementation may reduce the risk of childhood AL. The findings also suggest that the genotype homozygous for any of the MTHFR variants and carrying both MTRR variants could be a risk factor for AL.

Introduction In order to describe relapsed B‐cell non‐Hodgkin lymphoma and mature acute leukemia in children/adolescents treated with the Lymphomes Malins B (LMB) regimen and their outcome in the rituximab era, relapses in the French LMB2001 study were reviewed. Methods Between February 2001 and December 2011, 33 patients out of 773 (4.3%) relapsed; 27 had Burkitt lymphoma and six large B‐cell histology. Median age at diagnosis was 10.1 years. One patient was initially treated in risk group A, 21 in group B, and 11 in group C. Results Median time to relapse after diagnosis was 4.5 months (range 2.4‐13.6). Thirty‐two patients received salvage therapy. Twenty‐seven received rituximab mainly in addition to high‐dose cytarabine and etoposide (n = 18) and/or ifosfamide, carboplatin, and etoposide (n = 7). First‐line salvage chemotherapy response rate was 66% with 47% being complete remission (CR). Twenty‐one patients received high‐dose chemotherapy (HDC) followed by autologous (n = 13) or allogeneic (n = 8) transplant. With a median follow‐up of 6.8 years, the 5‐year survival rate after relapse was 36.4% (95% confidence interval [CI] 22‐53%). Twelve patients were still alive; all but one (group A) received consolidation treatment. Achieving CR before consolidation was significantly associated with better survival, with a 5‐year survival rate of 75% (95% CI 46.8‐91.1%) for patients in CR before HDC, 33% (95% CI 9.7‐70%) for patients in partial remission, and 0% for nonresponders (P = .033). Conclusion Survival of children/adolescents with mature B‐cell lymphoma/leukemia remains poor after relapse with no apparent improvement with rituximab. Response rates to salvage chemo‐immunotherapies are insufficient and new drugs are urgently needed to improve disease control.

PURPOSE A dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) regimen has been shown to deliver excellent survival for adults with primary mediastinal large B-cell lymphoma (PMLBL) without the use of radiotherapy. No international prospective evaluation of this regimen has previously been reported in children and adolescents. PATIENTS AND METHODS We conducted an international single-arm phase II trial involving patients younger than age 18 years with PMLBL who were to receive six courses of DA-EPOCH-R. The primary end point was event-free survival (EFS). Overall survival and toxicity were also assessed. This trial was registered (ClinicalTrials.gov identifier: NCT01516567 ). RESULTS Analyses were based on 46 patients. The median age was 15.4 years (interquartile range 14-16 years). The median follow-up was 59.0 months (interquartile range: 52.6-69.2 months). Fourteen events were observed (eight relapses or progressions (including three parenchymal CNS relapses), four residual lymphoma, and two second malignancies). The 4-year EFS was 69.6% (95% CI, 55.2 to 80.9), which did not differ from the rate observed historically ( P = .59). Seven deaths occurred (six disease-related and one second malignancy). The overall survival was 84.8% (95% CI, 71.8 to 92.4). Twenty-two patients (48%) reached dose levels ≥ 4. Nonhematologic adverse events grade ≥ 3 or cardiac adverse events grade ≥ 2 occurred in 47 of 276 (17%) courses and 30 of 46 patients (65%). CONCLUSION DA-EPOCH-R did not improve the EFS compared with a historical control in this first prospective multisite international study of children and adolescents with PMLBL. Further studies are required to determine the optimum therapy for children and adolescents with this lymphoma.

Bouttefroy, Nicolas André, and Virginie Gandemer participated in the study and data collection, and read and approved the manuscript as submitted.

To study the management of acute appendicitis in neutropenic patients, we retrospectively reviewed cases of acute appendicitis in neutropenic children treated for cancer. The patients' demographics, medical records, and outcomes were tracked. We compared nonoperative treatment versus emergency or delayed surgery. The cases of 30 patients with a mean age of 8.8 years in 12 French departments of Pediatric Hematology/Oncology between 1995 and 2013 were studied. Most patients (90%) were treated for hematological malignancies. Seven of the 30 children were successfully treated with exclusive medical treatment. Early surgery was performed in 6 patients, and the remaining 17 underwent combined management with a first-line antibiotic treatment and delayed appendectomy. Treatments were successful in all cases with transitory complications in only 3 patients. No death linked to infection was reported. Surgery was well tolerated even in the neutropenic period. Appendix perforation was a major risk factor of prolonged hospitalization. Histologic as well as bacteriologic and mycologic/parasitologic analyses were required in case of surgery. Analysis of diagnostic assessments showed the major importance of imaging (ultrasonography and tomography) on diagnosis confirmation. We could not come to a conclusion in the few numbers of reviewed cases because of a significant difference in management strategies, but we can conclude that early surgery after adequate supportive care is an acceptable modality of treatment and must be chosen in the face of life-threatening conditions.