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Introduction: Despite the rapid uptake of emicizumab in the paediatric haemophilia A (HA) population, real‐world data on the safety and efficacy is limited. Aim: To report on bleeding and safety in paediatric patients receiving emicizumab prophylaxis. Methods: Data were extracted from the multicentre prospective observational PedNet Registry (NCT02979119). Children with haemophilia A, and ≥50 FVIII exposures or inhibitors present receiving emicizumab maintenance therapy were analysed. Data were summarized as medians with interquartile range (IQR, P25–P75). Mean (95% confidence interval (CI)), annualized (joint) bleeding rate (A(J)BR) during emicizumab and ≤2 years before emicizumab prophylaxis were modelled and compared using negative binomial regression. Results: Total of 177 patients started emicizumab at median 8.6 years (IQR 4.8–13.1), most had no FVIII inhibitors (64%). Follow up before emicizumab was median: 1.68 years (IQR: 1.24–1.90) and during emicizumab: 1.32 years (IQR:.94–2.11). In patients without inhibitors, mean ABR reduced after starting emicizumab from 2.41 (CI 1.98–2.95) to 1.11 (CI.90–1.36, p <.001), while AJBR reduced from.74 (CI.56–.98) to.31 (CI.21–.46, p <.001). Concordantly, in patients with inhibitors, mean ABR reduced from 5.08 (CI 4.08–6.38) to.75 (CI.56–1.01, p <.001), while AJBR reduced from 1.90 (CI 1.42–2.58) to.34 (CI.21–.56, p <.001). Five emicizumab‐related adverse events were reported (3% of the cohort), including one patient with antidrug antibodies. Conclusion: This study showed improved bleeding control compared to previous treatment and a favourable safety profile during emicizumab therapy in paediatric haemophilia A patients. [ABSTRACT FROM AUTHOR]

Introduction: Of newly diagnosed cases of haemophilia B, the proportion of sporadic cases is usually 50% of severe cases and 25% of moderate/mild cases. However, cases presumed to be sporadic due to family history may not always be sporadic. Few case reports have been published on mosaicism in haemophilia B. Aim: The present study aimed to trace the origin of the pathogenic variant in a well‐defined cohort of sporadic cases of haemophilia B by haplotyping markers. It also aimed to determine the frequency of mosaicism in presumed non‐carrier mothers. Methods: The study group was 40 families, each with a sporadic case of haemophilia B analysed in two‐to‐three generations by Sanger sequencing, haplotyping and using the sensitive droplet digital polymerase chain reaction (ddPCR) technique. Results: In 31/40 (78%) of the families, the mother carried the same pathogenic variant as her son, while Sanger sequencing showed that 9/40 (22%) of the mothers did not carry this variant. Of these variants, 2/9 (22%) were shown to be mosaics by using the ddPCR technique. 16/21 carrier mothers, with samples from three generations available, had a de novo pathogenic variant of which 14 derived from the healthy maternal grandfather. Conclusion: The origin of the pathogenic variant in sporadic cases of haemophilia B is most often found in the X‐chromosome derived from the maternal grandfather or, less often, from the maternal grandmother. Mosaic females seem to be found at the same frequency as in haemophilia A but at a lower percentage of the pathogenic variant. [ABSTRACT FROM AUTHOR]

Background Patients and Methods Results Conclusions The authors report the prospective evaluation of reduced dose alkylator chemotherapy combined with radiotherapy for European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) standard risk nonalveolar rhabdomyosarcoma (NA‐RMS).Localized node negative Intergroup Rhabdomyosarcoma Study (IRS) II/III NA‐RMS at favorable sites (subgroup C), <25 years old, received five cycles of ifosfamide, vincristine, and dactinomycin (IVA) chemotherapy (30 g/m2 ifosfamide) and four cycles of vincristine and dactinomycin (if receiving radiotherapy), or nine cycles of IVA (54 g/m2 ifosfamide) ± radiotherapy. Delayed primary tumor excision was considered for IRS III tumors. The primary end points were event‐free survival (EFS) and overall survival (OS).From October 2005 to December 2016, 359 evaluable patients were recruited: orbit, 164 (45.7%); head and neck nonparameningeal, 77 (21.4%); and genitourinary non–bladder/prostate, 118 (32.9%). EFS and OS were 77.4% (95% confidence interval [CI], 72.5–81.6) and 93.5% (95% CI, 90.1–95.8), respectively. Lower dose alkylator chemotherapy and radiotherapy achieved 5‐year OS of 93.7% but the difference with higher dose alkylator chemotherapy +/‐ radiotherapy was not significant (p = 0.8003). Adjuvant radiotherapy improved EFS with 5‐year estimates of 84.7% versus 65.2% for nonirradiated (p < .0001), but not OS (p = .9298). Omitting radiotherapy for orbital tumors reduced OS (5‐year was 87.1% vs. 97.3% for irradiated, p = .0257). Following R0 resection (n = 60), radiotherapy did not significantly improve EFS or OS.Radiotherapy for local tumor control allows for reduction of cumulative dose of alkylators in EpSSG standard risk subgroup C RMS patients. The omission of radiotherapy did not affect OS in all patients except those with orbital RMS and was associated with inferior EFS. [ABSTRACT FROM AUTHOR]