PMC9744919_01
CAR-T-38 therapy response in the two patients with CML-BP. (A) This part showed the bone marrow morphological feature of patients 1 and 2 before (up) and 2 weeks after CAR-T-38 treatment (upper lower). After CAR-T-38 cell infusion, the patient 1 (left, lower) and 2 (right, lower) achieved CR. (B) The blasts were gated by using a CD45, side scatter (SS), and CD34-based gating strategy, but CD34+ leukemia had lost CD34 expression as the disease progressed to BP in these two patients, and the blasts were gated according to CD45/SS gating strategy (left). The blast (A population, tomato red) rates of bone marrow mononuclear cells (blank, middle and right plots) were 28.8% and 7.3 x 10-4 before and 2 weeks after CAR-T-38 treatment, respectively. This CD34- AML blast fraction expressed CD38, CD117, CD33, CD13, CD123, and HLA-DR. (C) Both E255K and T315I mutation disappeared in bone marrow 2 weeks after CAR-T cell infusion. (D) Dynamic changes of BCR::ABL1 expression level (IS) of patient 1 in the course of the disease. Patient 1 was resistant to multiple TKIs [imatinib (IM), dasatinib (DAS), nilotinib (NIL), and ponatinib (PON)], intensive chemotherapy with idarubicin and cytarabine (IA), and interferon-alpha (IFN). The level of BCR::ABL1 was reduced to 0, 1 week after CAR-T treatment.
fimmu-13-1012981-g001.jpg
PMC9744919_02_fimmu-13-1012981-g001.jpg
f1
One week after CAR-T-38 cell infusion, he achieved a CR ( Figure 1A ) and MRD-negative and BCR::ABL1-negative CR.
Dynamic changes after CAR-T-38 treatment. (A) The copies of CAR-T-38 cells in the peripheral blood measured by qPCR as the number of copies of lentiviral vector sequence per microgram of genomic DNA, which reached peak levels on days 4 and 6, respectively. (B) The neutrophil counts (left Y-axis) in patients 1 and 2 rose above 0.5 x 109 on days 14 and 7, respectively, and platelet counts (right Y-axis) of the two patients rose above 100 x 109 on day 14. (C) This part showed the changes of cytokines including IL-6, IL-10, TNFalpha, and IFNgamma concentrations after CAR-T-38 infusion. (D) This part showed the changes of c-reaction protein (left Y-axis) and ferritin (right Y-axis) concentrations after CAR-T-38 infusion.
fimmu-13-1012981-g002.jpg
PMC9744919_02_fimmu-13-1012981-g002.jpg
f2
CAR-T cell numbers in vivo reached peak on day 6 ( Figure 2A ), and he did not have prominent adverse events ( Figures 2B-D ).
PMC9744919_02
CAR-T-38 therapy response in the two patients with CML-BP. (A) This part showed the bone marrow morphological feature of patients 1 and 2 before (up) and 2 weeks after CAR-T-38 treatment (upper lower). After CAR-T-38 cell infusion, the patient 1 (left, lower) and 2 (right, lower) achieved CR. (B) The blasts were gated by using a CD45, side scatter (SS), and CD34-based gating strategy, but CD34+ leukemia had lost CD34 expression as the disease progressed to BP in these two patients, and the blasts were gated according to CD45/SS gating strategy (left). The blast (A population, tomato red) rates of bone marrow mononuclear cells (blank, middle and right plots) were 28.8% and 7.3 x 10-4 before and 2 weeks after CAR-T-38 treatment, respectively. This CD34- AML blast fraction expressed CD38, CD117, CD33, CD13, CD123, and HLA-DR. (C) Both E255K and T315I mutation disappeared in bone marrow 2 weeks after CAR-T cell infusion. (D) Dynamic changes of BCR::ABL1 expression level (IS) of patient 1 in the course of the disease. Patient 1 was resistant to multiple TKIs [imatinib (IM), dasatinib (DAS), nilotinib (NIL), and ponatinib (PON)], intensive chemotherapy with idarubicin and cytarabine (IA), and interferon-alpha (IFN). The level of BCR::ABL1 was reduced to 0, 1 week after CAR-T treatment.
fimmu-13-1012981-g001.jpg
PMC9744919_02_fimmu-13-1012981-g001.jpg
f1
One week after CAR-T-38 cell infusion, he achieved a CR ( Figure 1A ) and MRD-negative and BCR::ABL1-negative CR.
Dynamic changes after CAR-T-38 treatment. (A) The copies of CAR-T-38 cells in the peripheral blood measured by qPCR as the number of copies of lentiviral vector sequence per microgram of genomic DNA, which reached peak levels on days 4 and 6, respectively. (B) The neutrophil counts (left Y-axis) in patients 1 and 2 rose above 0.5 x 109 on days 14 and 7, respectively, and platelet counts (right Y-axis) of the two patients rose above 100 x 109 on day 14. (C) This part showed the changes of cytokines including IL-6, IL-10, TNFalpha, and IFNgamma concentrations after CAR-T-38 infusion. (D) This part showed the changes of c-reaction protein (left Y-axis) and ferritin (right Y-axis) concentrations after CAR-T-38 infusion.
fimmu-13-1012981-g002.jpg
PMC9744919_02_fimmu-13-1012981-g002.jpg
f2
CAR-T cell numbers in vivo reached peak on day 6 ( Figure 2A ), and he did not have prominent adverse events ( Figures 2B-D ).