Figure 2.
Differences in morphology and kinetics in SRs, NRs, and relapses. (A) Normal mature lymphocytes (top) and persistent blasts (bottom) in NR patient HP-9 (left). Representative CellaVision images at ×500 original magnification. ALC and blast kinetics in NR HP-9 (right). (B) Increase in atypical lymphocytes (left top, days 5-15), as blasts (left bottom) disappeared by day 13 in responder HP-83. Example of an apoptotic cell (with crenellated nucleus) after CAR-infusion is shown in a day-13 image. ALCs and blast kinetics in responder HP-83 (right). (C) Individual ALC curves and mean (black dashed line) in 72 SRs show characteristic ALC proliferation kinetics with initial lag phase, then marked expansion, followed by rapid contraction and persistence. (D) Individual ALC curves and mean in 7 NRs show decreased lymphocyte proliferation. (E) Individual ALC curves and mean in 27 (eventual) CD19-posRs. Dotted black lines indicate mean upper and lower limits of normal ALC. The y-axes are shown in linear scale, similar to ALC graphs in the electronic medical record (EPIC) and to highlight low-level peaks. (F) Violin plots depicting medians, quartile ranges, and distribution of various groups (left) show significantly (*P = .04, Kruskal-Wallis test) higher peak ALCs in SRs than in NRs, but not in SRs vs CD19-posRs (P = .1). Violin plots of ALC AUC1mo in various groups (left) showing significantly higher overall ALC expansion in SRs compared with NRs (***P = .0009) and CD19-posRs (*P = .013). (G) ROC analyses of peak ALC and ALC AUC1mo in SRs and NRs and ALC AUC1mo in SRs and CD19-posRs.

Differences in morphology and kinetics in SRs, NRs, and relapses. (A) Normal mature lymphocytes (top) and persistent blasts (bottom) in NR patient HP-9 (left). Representative CellaVision images at ×500 original magnification. ALC and blast kinetics in NR HP-9 (right). (B) Increase in atypical lymphocytes (left top, days 5-15), as blasts (left bottom) disappeared by day 13 in responder HP-83. Example of an apoptotic cell (with crenellated nucleus) after CAR-infusion is shown in a day-13 image. ALCs and blast kinetics in responder HP-83 (right). (C) Individual ALC curves and mean (black dashed line) in 72 SRs show characteristic ALC proliferation kinetics with initial lag phase, then marked expansion, followed by rapid contraction and persistence. (D) Individual ALC curves and mean in 7 NRs show decreased lymphocyte proliferation. (E) Individual ALC curves and mean in 27 (eventual) CD19-posRs. Dotted black lines indicate mean upper and lower limits of normal ALC. The y-axes are shown in linear scale, similar to ALC graphs in the electronic medical record (EPIC) and to highlight low-level peaks. (F) Violin plots depicting medians, quartile ranges, and distribution of various groups (left) show significantly (*P = .04, Kruskal-Wallis test) higher peak ALCs in SRs than in NRs, but not in SRs vs CD19-posRs (P = .1). Violin plots of ALC AUC1mo in various groups (left) showing significantly higher overall ALC expansion in SRs compared with NRs (***P = .0009) and CD19-posRs (*P = .013). (G) ROC analyses of peak ALC and ALC AUC1mo in SRs and NRs and ALC AUC1mo in SRs and CD19-posRs.

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