Prophylactic rFIXFc, administered every 1 to 2 weeks, resulted in low annualized bleeding rates in patients with hemophilia B. (Funded by Biogen Idec; ClinicalTrials.gov number, NCT01027364.).

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To explore the effects of immunotherapy in the International Society of Paediatric Oncology Europe Neuroblastoma Group SIOPEN high-risk neuroblastoma 1 trial (HR-NBL1 trial), two cohorts were studied: one prior to and one after the introduction of dinutuximab beta. All patients received standard induction and high-dose therapy (HDT) with autologous stem cell rescue (ASCR); the local control comprised surgery and radiotherapy to the primary tumour site, followed by isotretinoin. A landmark timepoint of 109 days, resulting from the median time between ASCR and initiation of immunotherapy, was used to define patients’ eligibility in the pre-immunotherapy analysis cohort. Median follow-up was 5.8 years (inter-quartile range (IQR): 4.2–8.2 years) for 844 eligible patients balanced for risk factors, such as age, sex, stage 4, MYCN amplification and response prior to HDT. The five-year event-free and overall survival (95% confidence interval (CI) of 466 patients not receiving immunotherapy was 42% (38–47%) and 50% (46–55%) but was 57% (51–62%) and 64% (59–69%) for 378 patients receiving immunotherapy (p < 0.001). A multivariate analysis identified absence of immunotherapy (p = 0.0002, hazard ratio (HR) 1.573); type of HDT (p = 0.0029, HR 1.431); less than complete response prior to maintenance therapy (p = 0.0043, HR 1.494) and >1 metastatic compartment at diagnosis (p < 0.001, HR 2.665) as risk factors for relapse or progression. Results suggest an important role for dinutuximab beta-based immunotherapy within the treatment concepts applied in HR-NBL1/SIOPEN.

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Summary Mesenchymal stem cells (MSCs) are an important cellular component of the bone marrow microenvironment for supporting haemopoiesis. However, their response to high‐dose chemotherapy remains unknown. We assessed the acute direct effects of individual chemotherapeutic agents on human MSCs (hMSCs). Using an in vitro culture system, the chemosensitivity of hMSCs was determined by XTT (2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulphophenyl)‐5‐[(phenylamino) carbonyl]‐2H‐tetrazolium hydroxide) assay in comparison with that of NB‐4 cells, a leukaemic cell line, and normal peripheral blood mononuclear cells. The recovery of cell numbers following exposure to chemotherapeutic agents and chemotherapy‐induced apoptosis of hMSCs were evaluated. Human MSCs were resistant to chemotherapeutic agents commonly used in bone marrow transplantation (BMT) (i.e. busulphan, cyclophosphamide and methotrexate). However, they were relatively sensitive to a panel of cytotoxic agents, such as paclitaxel, vincristine, etoposide and cytarabine. Furthermore, different recovery patterns were noted. There was sustained suppression in hMSCs following 3 d exposure to paclitaxel, cytarabine and etoposide. In contrast, significant recovery was seen in hMSCs treated with dexamethasone and vincristine respectively. Human MSCs have different patterns of response to a panel of chemotherapeutic agents commonly used in BMT or cancer therapy. Understanding this variation is important in optimizing conditioning regimens for BMT.