No abstract

BL-class fusions other than BCR-ABL1 characterize around 2-3% of precursor B-cell acute lymphoblastic leukemia. Case series indicated that patients suffering from these subtypes have a dismal outcome and may benefit from the introduction of tyrosine kinase inhibitors. We analyzed clinical characteristics and outcome of 46 ABL-class fusion positive cases other than BCR-ABL1 treated according to AIEOP-BFM (Associazione Italiana di Ematologia-Oncologia Pediatrica-Berlin-Frankfurt-Münster) ALL 2000 and 2009 protocols; 13 of them received a tyrosine kinase inhibitor (TKI) during different phases of treatment. ABL-class fusion positive cases had a poor early treatment response: minimal residual disease levels of ≥5x10 -4 were observed in 71.4% of patients after induction treatment and in 51.2% after consolidation phase. For the entire cohort of 46 cases, the 5-year probability of event-free survival was 49.1+8.9% and that of overall survival 69.6+7.8%; the cumulative incidence of relapse was 25.6+8.2% and treatment-related mortality (TRM) 20.8+6.8%. One out of 13 cases with TKI added to chemotherapy relapsed while eight of 33 cases

To study the prognostic relevance of rare genetic aberrations in acute myeloid leukemia (AML), such as t(16;21), international collaboration is required. Two different types of t(16;21) translocations can be distinguished: t(16;21)(p11;q22), resulting in the fusion gene; and t(16;21)(q24;q22), resulting in RUNX1-core binding factor (). We collected data on clinical and biological characteristics of 54 pediatric AML cases with t(16;21) rearrangements from 14 international collaborative study groups participating in the international Berlin-Frankfurt-Münster (I-BFM) AML study group. The AML-BFM cohort diagnosed between 1997 and 2013 was used as a reference cohort. (n = 23) had significantly lower median white blood cell count (12.5 × 10/L, = .03) compared with the reference cohort. rearranged AML (n = 31) had no predominant French-American-British (FAB) type, whereas 76% of had an M1/M2 FAB type (M1, M2), significantly different from the reference cohort ( = .004). Four-year event-free survival (EFS) of patients with was 7% (standard error [SE] = 5%), significantly lower compared with the reference cohort (51%, SE = 1%, < .001). Four-year EFS of was 77% (SE = 8%, = .06), significantly higher compared with the reference cohort. Cumulative incidence of relapse was 74% (SE = 8%) in , 0% (SE = 0%) in compared with 32% (SE = 1%) in the reference cohort ( < .001). Multivariate analysis identified both and as independent risk factors with hazard ratios of 1.9 ( < .0001) and 0.3 ( = .025), respectively. These results describe 2 clinically relevant distinct subtypes of pediatric AML. Similarly to other core-binding factor AMLs, patients with RUNX1-CBFA2T3 rearranged AML may benefit from stratification in the standard risk treatment, whereas patients with FUS-ERG rearranged AML should be considered high-risk.

Tremendous progress in the therapy of pediatric acute lymphoblastic leukemia (ALL) has been achieved through combination cytotoxic chemotherapy, leading to high cure rates, at the cost of significant life-threatening toxicity. The bispecific T-cell engager blinatumomab, recently approved for relapsed/refractory ALL, has a unique nonmyelotoxic toxicity profile. As blinatumomab causes B-cell depletion, the safety of its use during severe chemotherapy-induced toxicity is unclear. We report 11 pediatric patients with ALL, treated with blinatumomab following overwhelming chemotherapy-associated toxicity, with recovery of all patients and successful bridging to further antileukemia therapy. Blinatumomab can be considered for rare patients who cannot tolerate cytotoxic therapy. K E Y W O R D S blinatumomab, childhood acute lymphoblastic leukemia, immunotherapy, treatment-related toxicity Abbreviations: ALL, acute lymphoblastic leukemia; B-ALL, B-cell precursor acute lymphoblastic leukemia; DS, Down syndrome; MRD, minimal residual disease; R/R, relapsed/refractory.