PMC6826178_01
Mononuclear cells were collected from the peripheral blood on D-48; DECP chemotherapy on D-24;FC (fludarabine, 20 mg/m2 per day on D-5, D-4, and D-3;cyclophosphamide 600 mg/m2 on D-5);CAR-T cells were infused into the patient (CD19 on D0 and BCMA on D1 to D2);Tocilizumab (8 mg/kg) on D6 and D8.
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After the administration of regimen FC, the patient received consecutive infusions of CD19-CAR-T cells and BCMA-CAR-T cells (Figure 1). The same dose of tocilizumab was used on D8 as IL-6 reached the peak (11,403.2 pg/mL) (Figure 2D, Table 1).
(A) Body temperature changes after CAR-T cell infusion, with a maximum temperature on each day and the changes in SpO2; (B) The left thigh circumference (LTC), right thigh circumference (RTC), left calf circumference (LCC), and right calf circumference (RCC) were measured every day after thrombosis was formed; (C) The levels of PT, APTT, thrombin time (TT), D-Dimer, fibrinogen (FIB), fibrin degradation products (FDP), and antithrombin III (ATIII) during the CRS changed with the levels of C-reactive protein (CRP), interleukin-6 (IL-6), etc. After treatment with tocilizumab, both coagulative and CRS indicators dropped obviously; (D) Inflammatory cytokine levels after CAR-T cell infusion (IL-6, IL-10, TNF-alpha, and IFN-gamma); IL-6 level (11,403.2 pg/mL) peaked on D8.
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However, on the morning of D5, his body temperature rose to 39 C (Figure 2A). His left lower extremity suddenly swelled with pain, exceeding his right thigh by 12.3 cm in circumference (Figure 2B). The same dose of tocilizumab was used on D8 as IL-6 reached the peak (11,403.2 pg/mL) (Figure 2D, Table 1).
MRI results before and after CAR-T treatment. The mass in the left piriformis region was significantly smaller after CAR-T treatment. 1A and 1B (extramedullary relapse); 2A and 2B (one month after CAR-T); 3A and 3B (two months after CAR-T).
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On D60, MRI showed the mass in the left piriformis shrunk significantly (Figure 3).
The result of IL-6 gene First Generation Sequencing showed that thegenotype of -572C/G promoter polymorphisms was CC. The sequence is GGAACCGGTGAGACGTGGCAGAGCCACGCGGTGGCAAAAAGGAGTCACACACTCCACCTGGAGACGCCTTGAAGTAACTGCACGAAATTTGAGGGTGGCCAGGCAGTTCTACAACAGCCCCTCACAGGGAGAGCCAGAACACAGAAGAACTCAGATGACTGGTAGTATTACCTTCTTCATAATCCCAGGCTTGGGGGGCTGCGATGGAGTCAGAGGAAACTCAGTTCAGAACATCTTTGGTTTTTACAAATACAAATTAACTGGAACGCTAAATTCTAGCCTGTTAATCGGTTCACTGAAAATAATTCGGGCCGGTGCCACGGGTTGCCCGTAGCCGGAGCACCCCTCACAGCGGAGGGGCGGAAAATTGGGAAAACTACCCGCGTCGTTCTCCTTGGCTGCTGCAGATGTGAGCGCAATCGGGAGAGGTGAGTGGGAATATAAAACGAGGAGGGGGGAAAATAGCCCTTCATA.
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With the First Generation Sequencing, we extracted genomic DNA from the patient's peripheral blood to analyze the distribution of polymorphisms, finding that the genotype of -572C/G promoter polymorphisms was CC (Figure 4).