Clinical outcomes of hypomethylating agents and venetoclax in newly diagnosed unfit and relapsed/refractory paediatric, adolescent and young adult acute myeloid leukaemia patients.

Venetoclax (VEN) combined with hypomethylating agents (HMA) decitabine or azacitidine is used for adult acute myeloid leukaemia (AML), but its application in paediatric, adolescent and young adult (AYA) AML lacks prospective studies. We performed a retrospective chart review of paediatric and AYA AML patients treated with HMA + VEN at Cincinnati Children's Hospital Medical Centre. Twenty-seven patients received 30 HMA + VEN treatment courses for relapsed/refractory (R/R, n = 21) or newly diagnosed (n = 9) AML due to ineligibility for intensive chemotherapy. The R/R cohort had high-risk cytomolecular genetic alterations and prior extensive treatments, with 50% (n = 9) of relapse patients (n = 18) having undergone haematopoietic stem cell transplantation (HSCT). Venetoclax treatment using the 400 mg adult exposure-equivelant dosing (AED) had a median duration of 21 days (range 7-30 days). Grade 3-4 toxicities included neutropenia (90%), anaemia (64%), thrombocytopenia (64%) and febrile neutropenia (44%). The overall complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 73% (77% minimal residual disease [MRD] negativity <0.1%), with 60% undergoing HSCT. Among newly diagnosed patients (n = 9), 89% achieved CR/CRi (78% MRD negativity) and 78% proceeded to HSCT. The R/R cohort (n = 21) showed a 67% CR/CRi rate (71% MRD negativity), with 52% undergoing HSCT. These findings support the safety and efficacy of HMA + VEN in paediatric/AYA AML, indicating it as a viable option for patients unfit for intensive chemotherapy. Further studies are necessary to determine optimal venetoclax dosing, chemotherapy combinations and pharmacokinetics in this population.

IDH-mutant brainstem gliomas in adolescent and young adult patients: Report of three cases and review of the literature.

Isocitrate dehydrogenase (IDH) mutations are rare in pediatric and adolescent gliomas. We recently identified three adolescent/young adult (AYA) patients with IDH-mutant low grade gliomas of the brainstem with several key clinicopathologic and molecular features in common. We discuss these three cases and review the current literature.

Atrial Fibrillation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.

PURPOSE: To examine the incidence and risk factors for de novo atrial fibrillation (AF) after allogeneic hematopoietic cell transplantation (HCT) and to describe the impact of AF on HCT-related outcomes. METHODS: A retrospective cohort study design was used to examine AF and associated outcomes in 487 patients who underwent allogeneic HCT from 2014 to 2016 and to characterize patient- and HCT-related risk factors. A nested case-control study design was used to describe the association between pre-HCT echocardiographic measures and future AF events. RESULTS: The median age at HCT was 52.4 years (18.1-78.6); the median time to AF was 117.5 days (4.0-1,405.0). The 5-year cumulative incidence of AF was 10.6%. Older (≥ 50 years) age (hazard ratio [HR], 2.76; 95% CI, 1.37 to 5.58), HLA-unrelated donor (HR, 2.20; 95% CI, 1.18 to 4.12), dyslipidemia (HR, 2.40; 95% CI, 1.23 to 4.68), and pre-HCT prolonged QTc interval (HR, 2.55; 95% CI, 1.38 to 4.72) were independent risk factors for AF. Despite having comparable left ventricular systolic function, patients who developed AF were significantly more likely to have lower left atrial ejection fraction, left atrial reservoir function, and elevated tricuspid regurgitant jet velocity prior to HCT, compared with patients who did not. The incidence rate of stroke after AF was 143 per 1,000 person-years. In adjusted analyses, AF was associated with a 12.8-fold (HR, 12.76; 95% CI, 8.76 to 18.57) risk of all-cause mortality and 15.8-fold (HR, 15.78; 95% CI, 8.70 to 28.62) risk of nonrelapse mortality. CONCLUSION: The burden of AF after allogeneic HCT population is substantial, and the development of AF is associated with poor survival. We identified important associations between patient demographics, pre-HCT cardiac parameters, HCT-related exposures, and risk of AF, setting the stage for targeted prevention strategies during and after HCT.