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Key Points EBF1-PDGFRB fusion accounts for ∼0.5% of B-cell precursor acute lymphoblastic leukemia and 2.7% of the B-other subtype. EBF1-PDGFRB-positive patients are MRD positive and are slow early responders who respond to imatinib.

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9/l. Relapse (14 patients) and adenoviral (six patients) or fungal infections (four patients) were the major causes of death. Haploidentical stem cell transplantation can produce medium term disease-free survival in a proportion of children with high-risk or relapsed acute leukaemia. None of the nine patients with acute myeloid leukaemia not in remission have survived.

Trials with second generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but are associated with risk of cytokine release syndrome (CRS). Instead, we studied the use of donor Epstein-Barr virus-specific T-cells (EBV CTL) transduced with a first generation CD19CAR, relying on the endogenous T-cell receptor for proliferation. We conducted a multi-center phase I/II study of donor CD19CAR transduced EBV CTL in pediatric acute lymphoblastic leukaemia (ALL). Patients were eligible pre-emptively if they developed molecular relapse (>5 × 10) post first stem cell transplant (SCT), or prophylactically post second SCT. An initial cohort showed poor expansion/persistence. We therefore investigated EBV-directed vaccination to enhance expansion/persistence. Eleven patients were treated. No CRS, neurotoxicity or graft versus host disease (GVHD) was observed. At 1 month, 5 patients were in CR (4 continuing, 1 de novo), 1 PR, 3 had stable disease and 3 no response. At a median follow-up of 12 months, 10 of 11 have relapsed, 2 are alive with disease and 1 alive in CR 3 years. Although CD19CAR CTL expansion was poor, persistence was enhanced by vaccination. Median persistence was 0 (range: 0-28) days without vaccination compared to 56 (range: 0-221) days with vaccination (P=0.06). This study demonstrates the feasibility of multi-center studies of CAR T cell therapy and the potential for enhancing persistence with vaccination.

Summary Clofarabine is a second‐generation purine nucleoside analogue, which has shown promising activity in relapsed and refractory paediatric acute lymphoblastic leukaemia (ALL). This report summarizes the early United Kingdom experience of clofarabine for the treatment of paediatric ALL in 23 patients, outside of the context of a clinical trial. Our results demonstrated that clofarabine‐based chemotherapy regimes were effective and well‐tolerated in this heavily pre‐treated group, with an overall response rate of 67% when used in combination regimes. Responses were seen in both B and T cell disease and in patients with adverse cytogenetics.

Patients with an ABL-class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post-induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL-class patients who did and did not receive a TKI in first remission to be compared. ABL-class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0Á009).

We report outcomes for 44 children who underwent stem cell transplantation (SCT) for refractory AML in the UK between 2000 and 2012. Median age at SCT was 11.5 years. Twenty-three patients had primary refractory and 21 relapsed refractory AML. Refractory disease was confirmed by cytogenetics/molecular genetics in 24 cases. Median follow-up of the whole cohort is 6.8 years (2.1-14.9 years). Thirty patients (68%) achieved a CR following SCT. Transplant-related mortality at 1 year was 18%. Acute GVHD incidence was 52% (grade ⩾III 19%), chronic 7%. Relapse was the major cause of treatment failure and occurred in 32% of patients at a median of 61 days post SCT. Five-year overall survival and leukemia-free survival (LFS) were 43% (95% CI 31-61%). All patients with favorable cytogenetics (n=6) are alive in CR. Outcomes in patients with primary refractory disease were equivalent to those with relapsed refractory AML. Blast percentage ⩽30% in the BM pre-SCT, myeloablative conditioning and acute GVHD proved to be favorable prognostic features. We could stratify patients according to age ⩾10 years and >30% blasts in BM pre-SCT. Patients with none/one of these risk factors were highly salvageable (5 years LFS 53%) whereas those with both factors had a very poor prognosis (5 years LFS 10%). This may facilitate decision making on whether it is appropriate to consider transplant in such patients.