Differential impact of drugs on the outcome of ETV6-RUNX1 positive childhood B-cell precursor acute lymphoblastic leukaemia : results of the EORTC CLG 58881 and 58951 trials

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Long-Term Survivor with Intrathecal and Intravenous Trastuzumab Treatment in Metastatic Breast Cancer

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Utilisation concomitante du nivolumab et d’immunosuppresseurs chez un patient greffé rénal

International audienceIntroduction: Immune-checkpoint inhibitors have been approved for first and second line treatments of metastatic non-small cell lung cancer based on the results of several phase III trials. Patients with organ transplantation were excluded from these studies because checkpoint inhibitors could activate allo-reactive T cells leading to acute graft rejection.Case report: A 71-year-old Caucasian-male was diagnosed with stage IV pulmonary adenocarcinoma with multiple metastases, without molecular alteration and negative PD-L1 status. He had a left kidney transplant, and his immunosuppressive regimen consisted of sirolimus and mycophenolate mofetil. After failure of two therapeutic lines (carboplatin-paclitaxel and erlotinib) a multidisciplinary oncology meeting with the nephrologist started third line treatment with nivolumab 3mg/kg every 15 days, with no modification of the immunosuppressive treatment. The patient received a total of 14 injections of nivolumab with stable disease but treatment was discontinued due to acute rejection of the transplanted kidney 6 months later, without need for dialysis. The patient died of a chylothorax related to progression of the tumour 12 months after initiation of nivolumab.Conclusion: Immune checkpoint inhibitors are a potential treatment for solid organ transplant patients despite the risk of graft rejection

CNS-3 status remains an independent adverse prognosis factor in children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: Results of EORTC Children Leukemia Group study 58951

International audienceTo evaluate the prognostic significance of initial central nervous system (CNS) involvement of children with acute lymphoblastic leukemia (ALL) enrolled in the EORTC 58951 trial.Patients and methods: From 1998 to 2008, 1930 ALL patients were included in the randomized EORTC 58951 trial. Overall treatment intensity was adjusted according to known prognostic factors including the level of minimal residual disease after induction treatment. CNS-directed therapy comprised four to 11 courses of i.v. methotrexate (5g/m2), and 10 to 19 intrathecal chemotherapy injections, depending on risk group and CNS status. Cranial irradiation was omitted for all patients.Results: The overall 8-year event-free survival (EFS) and overall survival (OS) rates were 81.3% and 88.1%, respectively. In the CNS-1, TPL+, CNS-2, and CNS-3 groups, the 8-year EFS rates were 82.1%, 77.1%, 78.3%, and 57.4%, respectively. Multivariable analysis indicated that initial CNS-3 status, but not CNS-2 or TLP+, was an independent adverse predictor of outcome. The 8-year incidence of isolated CNS relapse was 1.7% and of isolated or combined CNS relapse it was 3.7%. NCI high-risk group, male sex, CNS-2 and CNS-3 status were independent predictors for a higher incidence of any CNS relapse.Conclusions: CNS-3 status remains associated with poor prognosis and requires intensification of both systemic and CNS-directed therapy. This trial was registered at https://clinicaltrials.gov/under/NCT00003728