Frey NV, Shaw PA, Hexner EO, et al. - Given children with relapsed or chemotherapy refractory (r/r) B-cell acute lymphoblastic leukemia (ALL) have demonstrated 81% response rate when treated with anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel (CTL019), and cytokine release syndrome (CRS) represents life-threatening treatment-associated toxicity that limits the complete treatment potential in adults, so, researchers assessed results for adults with r/r ALL managed with an optimized CTL019 dosing and CRS management strategy. In 1 of 2 trials, CTL019 was administered to adults with r/r B-cell ALL. The participants were managed with lymphodepletion followed by CTL019 as either a one-time infusion or fractionated infusions split over 3 days (day 1, 10%; day 2, 30%; day 3, 60%), which permitted for day 2 and day 3 doses to be held for early CRS. A 33% complete remission (CR) rate and manageable toxicity were observed in the low-dose cohort (n = 9), which received single or fractionated dosing. Three patients attained CR in the high-dose single infusion cohort. A 90% CR rate and manageable CRS was observed in 20 patients in the high-dose fractionated (HDF) cohort. The highest survival was experienced by the HDF cohort, with a 2-year overall survival and event-free survival of 73% and 49.5%, respectively. Overall, the use of fractionated dosing of CTL019 with intrapatient dose modification enabled the optimization of safety without compromising efficacy in adults with r/r ALL.