PURPOSE CD19-targeted chimeric antigen receptor T cells (CD19-CAR) and blinatumomab effectively induce remission in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) but are also associated with CD19 antigen modulation. There are limited data regarding the impact of prior blinatumomab exposure on subsequent CD19-CAR outcomes. PATIENTS AND METHODS We conducted a multicenter, retrospective review of children and young adults with relapsed or refractory ALL who received CD19-CAR between 2012 and 2019. Primary objectives addressed 6-month relapse-free survival (RFS) and event-free survival (EFS), stratified by blinatumomab use. Secondary objectives included comparison of longer-term survival outcomes, complete remission rates, CD19 modulation, and identification of factors associated with EFS. RESULTS Of 420 patients (median age, 12.7 years; interquartile range, 7.1-17.5) treated with commercial tisagenlecleucel or one of three investigational CD19-CAR constructs, 77 (18.3%) received prior blinatumomab. Blinatumomab-exposed patients more frequently harbored KMT2A rearrangements and underwent a prior stem-cell transplant than blinatumomab-naïve patients. Among patients evaluable for CD19-CAR response (n = 412), blinatumomab nonresponders had lower complete remission rates to CD19-CAR (20 of 31, 64.5%) than blinatumomab responders (39 of 42, 92.9%) or blinatumomab-naive patients (317 of 339, 93.5%), P < .0001. Following CD19-CAR, blinatumomab nonresponders had worse 6-month EFS (27.3%; 95% CI, 13.6 to 43.0) compared with blinatumomab responders (66.9%; 95% CI, 50.6 to 78.9; P < .0001) or blinatumomab-naïve patients (72.6%; 95% CI, 67.5 to 77; P < .0001) and worse RFS. High-disease burden independently associated with inferior EFS. CD19-dim or partial expression (preinfusion) was more frequently seen in blinatumomab-exposed patients (13.3% v 6.5%; P = .06) and associated with lower EFS and RFS. CONCLUSION With the largest series to date in pediatric CD19-CAR, and, to our knowledge, the first to study the impact of sequential CD19 targeting, we demonstrate that blinatumomab nonresponse and high-disease burden were independently associated with worse RFS and EFS, identifying important indicators of long-term outcomes following CD19-CAR.

The energy distribution of ballistic electrons in a dc/rf hybrid parallel-plate capacitively coupled plasma reactor was measured. Ballistic electrons originated as secondaries produced by ion and electron bombardment of the electrodes. The energy distribution of ballistic electrons peaked at the value of the negative bias applied to the dc electrode. As that bias became more negative, the ballistic electron current on the rf substrate electrode increased dramatically. The ion current on the dc electrode also increased.

The effect of shear stress on the foaming process has been studied using the Foaming Process Simulator developed previously. The polymer samples were saturated with gas in the test chamber. A rotor was used to apply shear stress to the polymer samples. Foams were obtained by releasing the pressure quickly. Polystyrene. Hled and unfilled, was used as the material. The cell density was analyzed with a scanning electron microscope. It was found that the cell density was s - -cantly increased by introducing shear stress. The higher the shear stress, the more significant the effect. A cell stretch model has been developed to explain the cell nucleation enhancement with shear stress. The nucleation sites are stretched under the shear stress. The stretched nuclei are much easier to expand for cell formation owing to their larger surface areas and non-spherical shapes. The model prediction shows the same tendency of the effect of shear stress observed in the experiment. The key issue with shear stress nucleation is the transformation of mechanical shear energy into surface energy.

Relapse following chimeric antigen receptor (CAR) T-cell therapy directed against CD19 for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) remains a significant challenge. Three main patterns of relapse predominate: CD19 positive (CD19pos) relapse, CD19 negative (CD19neg) relapse, and lineage switch (LS). Development and validation of risk factors that predict relapse phenotype could help define potential pre- or post-CAR T-cell infusion interventions aimed at decreasing relapse. Our group sought to extensively characterize pre-infusion risk factors associated with the development of each relapse pattern via a multicenter, retrospective review of children and young adults with r/r B-ALL treated with a murine-based CD19-CAR construct. Of 420 CAR-treated patients, 166 (39.5%) relapsed, including 83 (50%) CD19pos, 68 (41%) CD19neg, and 12 (7.2%) LS relapses. A greater cumulative number of prior complete remissions was associated with CD19pos relapses, whereas high pre-infusion disease burden, prior blinatumomab non-response, older age, and 4-1BB CAR construct were associated with CD19neg relapses. The presence of a KMT2A rearrangement was the only pre-infusion risk factor associated with LS. The median overall survival following a post-CAR relapse was 11.9 months (95% CI 9-17 months) and was particularly dismal in patients experiencing a LS, with no long-term survivors following this pattern of relapse. Given the poor outcomes for those with post-CAR relapse, study of relapse prevention strategies, such as consolidative hematopoietic stem cell transplant, is critical and warrants further investigation on prospective clinical trials.