Summary Background Children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma achieve an event-free survival at 5 years of about 90% after treatment with vincristine, etoposide, prednisone, and doxorubicin (OEPA) followed by cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) and radiotherapy, but long-term treatment effects affect survival and quality of life. We aimed to investigate whether radiotherapy can be omitted in patients with morphological and metabolic adequate response to OEPA and whether modified consolidation chemotherapy reduces gonadotoxicity. Methods Our study was designed as a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial, and was carried out at 186 hospital sites across 16 European countries. Children and adolescents with newly diagnosed intermediate-stage (treatment group 2) and advanced-stage (treatment group 3) classical Hodgkin lymphoma who were younger than 18 years and stratified according to risk using Ann Arbor disease stages IIAE, IIB, IIBE, IIIA, IIIAE, IIIB, IIIBE, and all stages IV (A, B, AE, and BE) were included in the study. Patients with early disease (treatment group 1) were excluded from this analysis. All patients were treated with two cycles of OEPA (1·5 mg/m 2 vincristine taken intravenously capped at 2 mg, on days 1, 8, and 15; 125 mg/m 2 etoposide taken intravenously on days 1–5; 60 mg/m 2 prednisone taken orally on days 1–15; and 40 mg/m 2 doxorubicin taken intravenously on days 1 and 15). Patients were randomly assigned to two (treatment group 2) or four (treatment group 3) cycles of COPP (500 mg/m 2 cyclophosphamide taken intravenously on days 1 and 8; 1·5 mg/m 2 vincristine taken intravenously capped at 2 mg, on days 1 and 8; 40 mg/m 2 prednisone taken orally on days 1 to 15; and 100 mg/m 2 procarbazine taken orally on days 1 to 15) or COPDAC, which was identical to COPP except that 250 mg/m 2 dacarbazine administered intravenously on days 1 to 3 replaced procarbazine. The method of randomisation (1:1) was minimisation with stochastic component and was centrally stratified by treatment group, country, trial sites, and sex. The primary endpoint was event-free survival, defined as time from treatment start until the first of the following events: death from any cause, progression or relapse of classical Hodgkin lymphoma, or occurrence of secondary malignancy. The primary objectives were maintaining 90% event-free survival at 5 years in patients with adequate response to OEPA treated without radiotherapy and to exclude a decrease of 8% in event-free survival at 5 years in the embedded COPDAC versus COPP randomisation to show non-inferiority of COPDAC. Efficacy ana...

Anthracyclines have contributed significantly to the increased cure rate in pediatric oncology. Cardiac toxicity is an important late effect after anthracycline treatment and is thought to occur by reactive oxygen species mediated cardiac damage. We hypothesized that deactivating variants of superoxide dismutase II (SOD2) [rs4880 (-9Val > Ala)], catalase (CAT) [rs1001179 (-262C > T) and rs10836235 (c.66 + 78C > T)], GSTT1, and GSTM1 may increase the risk of developing cardiac toxicity, in patients exposed to anthracyclines. The hypothesis was tested in a cohort of 76 long-term survivals of acute lymphoblastic leukemia in childhood. Cardiac damage was evaluated as an attributive variable and compared to gene polymorphisms. In our study group, we show statistically significant correlation between CC homozygosity for CAT (rs10836235 (c.66 + 78C > T)) and cardiac damage after anthracycline exposure (p = 0.020). We found no statistically significant correlation between cardiac damage after anthracycline exposure and deactivating variants of SOD2 [rs4880 (-9Val > Ala)], CAT [rs1001179 (-262C > T), GSTT1, and GSTM1.

l-asparaginase is an effective antineoplastic agent used in chemotherapy of acute lymphoblastic leukemia. The drug effect may be compromised by an elicited immune response, resulting in the production of anti-asparaginase antibodies causing an anaphylactic reaction or silent inactivation of the enzyme. To elucidate possible genetic predisposition for inter-individual differences in asparaginase hypersensitivity, we studied single nucleotide polymorphisms (SNPs) in the GRIA1 gene in 146 pediatric patients treated with l-asparaginase. Allergic reaction to l-asparaginase occurred in 49.3% of patients. We observed a statistically significant association between SNPs in the GRIA1 gene and the occurrence of asparaginase allergy: rs4958351 with p = 0.003, rs4958676 with p = 0.005, rs6889909 with p = 0.005, rs6890057 with p = 0.005 and rs10070447 with p = 0.006. We found a statistically significant correlation between asparaginase allergy and event-free survival (p-value 0.005).

As hMPV can cause severe pneumonia in immunocompromised patients and due to the reports of effective treatment with ribavirin, clinical studies to elucidate the role of ribavirin in treatment of hMPV pneumonia may be needed.

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