Patient outcomes and piggyBac CAR19 T-cell expansion and persistence after infusion of escalating doses. (A) Clinical trial schema. Patients with relapsed or refractory B-cell malignancies post–allogeneic HSCT (Allo HSCT) received up to 3 escalating doses of HLA-matched sibling donor-derived piggyBac CAR19 T cells at least 1 month apart. Trial eligibility was assessed at enrollment and immediately before infusion. Those ineligible for infusion could elect to receive CAR19 T cells under the Therapeutic Goods of Australia Special Access Scheme (SAS) off-trial. (B) Swimmer plot showing disease response to escalating doses of donor-derived piggyBac CAR19 T cells in each patient. (C) Serial PET-CT scan images showing development of CAR19 T-cell lymphoma in 2 patients in CR of B cell malignancy. Patient 2 died of complications of CAR19 T-cell lymphoma and its treatment; patient 8 achieved CR of CAR19 T-cell lymphoma with 4 cycles of augmented CHOP chemotherapy, and remains in CR post–second allogeneic HSCT. Blue arrow, site of original disease for patient 2; red arrows, sites of CAR T-cell lymphoma for each patient. (D) Donor-derived piggyBac CAR19 T-cell expansion and persistence in the peripheral blood of each patient was assessed by flow cytometry. Data for the 2 patients who developed a CAR T-cell lymphoma are highlighted. chemo, chemotherapy; Cyclo, cyclophosphamide; DLBCL, diffuse large B-cell lymphoma; Flu, fludarabine; sCRS, severe CRS.