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Additional data on blast phase (BP) chronic myeloid leukaemia (CML) in children and adolescents is essential for improving diagnostic and therapeutic approaches of this rare but serious condition. Here, we describe distinct clinical and genetic characteristics of 18 paediatric patients with de novo (n = 10) and secondary (n = 8) BP CML enrolled in the CML-PAED-II trial and registry. Our findings suggest that paediatric patients exhibit a diverse cytogenetic profile compared to adults with BP CML. In addition, patients with de novo BP CML in this cohort presented at a younger age, whereas patients with secondary BP CML more often harboured complex karyotypes.

Ponatinib has proven to be effective in adults with Philadelphia chromosome-positive leukaemias, but data in paediatrics are scarce. Among paediatric patients with chronic myeloid leukaemia (n = 9) or acute lymphoblastic leukaemia (n = 12) treated with varying doses of ponatinib in 13 centres, 71% showed a decrease in disease burden after a median of three months. Ponatinib was well tolerated, with grade 3 toxicities occurring in 29% of patients. Toxicities were similar to those reported in adults, with the exception of arterial thrombotic events, which were not observed. Ponatinib has a favourable safety profile in this paediatric cohort, but dose-finding studies are needed.

Instituto Gonc alo Moniz- Fundacao Oswaldo Cruz (IGM-FIOCRUZ) and the Hospital da Crianc a das Obras Sociais Irma Dulce (HCOSID) approved this study, with protocol number 0016.0.225.000-09.

Summary This multicenter study used the Shanghai Children's Medical Center (SCMC)-ALL-2005 protocol for treatment of young patients (

Keywords: stem cell transplantation; paediatric patients; idiopathic severe aplastic anaemia

Summary Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a rare subtype associated with FLT3-internal tandem duplication (ITD) and poor outcomes. The clinical outcomes of paediatric patients with t(6;9) with and without FLT3-ITD treated on six consecutive cooperative trails were evaluated. In contrast to patients without t(6;9), those with t(6;9) had a significantly lower complete remission rate, higher relapse rate (RR), and poor overall survival (OS). Within t(6;9) patients, those with and without FLT3-ITD had an OS of 40% and 27% respectively (P > 0·9), demonstrating that t(6;9) is a high-risk cytogenetic feature in paediatric AML and its clinical impact is independent of the presence of FLT3-ITD.

SummaryTo evaluate the role of intravenous immunoglobulin (IVIg) in plateletapoptosis in paediatric immune thrombocytopenia, we investigated theplatelets of 20 paediatric patients with acute immune thrombocytopenia(ITP), before and after IVIg treatment. Healthy children with platelet countsin the normal range and children with thrombocytopenia due tochemotherapy were enrolled as controls. All ITP patients presented withplatelet counts 20 · 10 9 /l in all patients. ITPpatients had significantly increased proportions of platelets with activatedcaspase-3, -8 and -9, with PS exposure, and with decreased DWm, anddemonstrated increased microparticle formation. Except for DWm, thesemarkers for apoptosis were reduced by IVIg treatment. Platelets of childrenwith thrombocytopenia after chemotherapy also demonstrated increasedmicroparticle formation and decreased DWm, but no activation of caspases 3,8 and 9 or PS exposure. In conclusion, in acute paediatric ITP, enhancedplatelet apoptosis is seen at diagnosis that normalizes after IVIg treatment.Keywords: childhood ITP, IVIg, platelet apoptosis, caspase-3, phosphatidyl-serine exposure

The prognostic role of CD20 expression and Epstein-Barr virus (EBV) positivity in post-transplant lymphoproliferative disease (PTLD) after solid organ transplantation (SOT) in paediatric patients is poorly understood. We retrospectively examined the relationship of CD20 and EBV with the time interval from SOT to PTLD diagnosis, and PTLD-related event-free (EFS) and overall survival (OS) in 45 consecutive PTLD patients (≤25 years) following SOT. These 45 paediatric SOT patients (28 heart, 11 liver, six kidney) were diagnosed with PTLD 45 months (mean; SD 43; range 4-153; median 24·5) after SOT, with PTLD diagnosis at 118 months (mean) (SD 77; range 14-287) of age. Of 40 evaluable tumours (11 monomorphic, 19 polymorphic, five early lesions, five rare subtypes), 32 (80%) had detectable EBV and 28 (70%) were classified as CD20(+) . Patients whose PTLD expressed CD20 or EBV had shorter intervals between SOT and PTLD onset (28 vs. 64 or 77 months for CD20 and EBV respectively) (P < 0·02), even after adjusting for age at SOT. Patients with CD20(+) tumours had higher 5-year PTLD-related EFS (83·7% vs. 28·6%, P < 0·001) and OS (95·8% vs. 56·3%, P = 0·01). EBV expression was unrelated to PTLD-related EFS or OS. CD20 expression is associated with timing of development of PTLD and predicts survival in PTLD diagnosed following paediatric SOT.

International audience; High-throughput sequencing (HTS) is considered a technical revolution that has improved our knowledge of lymphoid and autoimmune diseases, changing our approach to leukaemia both at diagnosis and during follow-up. As part of an immunoglobulin/T cell receptor-based minimal residual disease (MRD) assessment of acute lymphoblastic leukaemia patients, we assessed the performance and feasibility of the replacement of the first steps of the approach based on DNA isolation and Sanger sequencing, using a HTS protocol combined with bioinformatics analysis and visualization using the Vidjil software. We prospectively analysed the diagnostic and relapse samples of 34 paediatric patients, thus identifying 125 leukaemic clones with recombinations on multiple loci (TRG, TRD, IGH and IGK), including Dd2/Dd3 and Intron/KDE rearrangements. Sequencing failures were halved (14% vs. 34%, P = 0.0007), enabling more patients to be monitored. Furthermore, more markers per patient could be monitored, reducing the probability of false negative MRD results. The whole analysis, from sample receipt to clinical validation, was shorter than our current diagnostic protocol, with equal resources. V(D)J recombination was successfully assigned by the software, even for unusual recombinations. This study emphasizes the progress that HTS with adapted bioinformatics tools can bring to the diagnosis of leukaemia patients.

Summary. The Platelet Function Analyzer (PFA-100®) was used to measure platelet function in paediatric patients with destructive versus underproduction thrombocytopenia. Closure time (CT) and total volume (TV) measurements with standard 150 μm apertures discriminated between patients with similar platelet counts from 30 to 150 × 109/l. However, at platelet counts

The guideline group regarding the diagnosis and management of myelofibrosis was selected to be representative of UK-based medical experts, together with a contribution from a single expert from the USA. MEDLINE and EMBASE were searched systematically for publications in English from 1966 until August 2011 using a variety of key words. The writing group produced the draft guideline, which was subsequently revised by consensus of the members of the General Haematology and Haemato-oncology Task Forces of the British Committee for Standards in Haematology (BCSH). The guideline was then reviewed by a sounding board of UK haematologists, the BCSH and the British Society for Haematology Committee and comments incorporated where appropriate. The criteria used to state levels and grades of evidence are as outlined in the Procedure for Guidelines commissioned by the BCSH; the 'GRADE' system was used to score strength and quality of evidence. The objective of this guideline is to provide healthcare professionals with clear guidance on the investigation and management of primary myelofibrosis, as well as post-polycythaemic myelofibrosis (post-PV MF) and post-thrombocythemic myelofibrosis (post-ET MF) in both adult and paediatric patients. © 2012 Blackwell Publishing Ltd.

Thrombotic thrombocytopenic purpura (TTP) is, in most cases, treatable with plasma exchange therapy (PLEX). Rarely, patients do not respond to PLEX or develop refractory disease despite an initial remission. In these cases, treatment options are limited and the response to established alternative therapies is often disappointing. We report the case of a paediatric patient with TTP who developed refractory disease after an initial response to PLEX. She was subsequently treated with cyclosporine A and showed an immediate and sustained response. CSA may be a safe and effective therapy for patients with refractory TTP and should be studied in randomized, prospective clinical trials.

Summary. In a prospective study, we evaluated the role of early treatment with ganciclovir of human cytomegalvirus (HCMV) pp65-antigenaemia, as well as the risk factors related to the infection in 48 paediatric patients given an allogeneic bone marrow transplantation (BMT). HCMV infection occurred in 24 children, the overall actuarial risk of infection at 120 d being 51%. Development of acute graft-versus-host disease (GVHD), steroid therapy and serological status of both recipient and donor were the most powerful predictors of HCMV infection, none of the six seronegative patient/donor pairs developing HCMV infection. Considering only the seropositive recipients and patients given a seropositive marrow (42 cases), the actuarial risk of developing HCMV antigenaemia in patients with acute GVHD was 76%v 27% in those with or without GVHD (P < 0.005) and 79%v 15% respectively in patients who did or did not receive steroid therapy (P < 0.001). HCMV disease developed in 5/24 children with pp65-antigen-aemia, which was detected before diagnosis in all cases but one. All patients with pp65-positive cells were treated with ganciclovir at a dose of 5 mg/kg twice daily for 14d. In patients without acute GVHD no maintenance therapy was adminis-tered, whereas children with active acute GVHD were given additional therapy with ganciclovir at a dose of 5 mg/kg/d for 14d. Ganciclovir produced complete clearing of viraemia and antigenaemia, with some patients presenting recurrences of antigenaemia, which were treated according to the above-mentioned schedule. Likewise, HCMV disease completely resolved after treatment with ganciclovir and no patients died from HCMV-related interstitial pneumonia. Our results suggest that an early short-term therapy with ganciclovir after demonstration of antigenaemia can be effective in reducing or abolishing HCMV-related mortality. This approach elim-inates the use of ganciclovir in patients not presenting HCMV reactivation and therefore not benefiting from therapy. The administration of ganciclovir limited to the period needed to obtain antigenaemia clearance could also have the advantage of reducing myelotoxicity.