PMC7098167_01
FISH analysis of the bone marrow. (A) yellow signal indicates negative CRLF2 rearrangement; (B) two signals of red and green indicate CRLF2 abnormal rearrangement.
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Next generation sequence analysis of the patient's bone marrow and oral mucosa revealed positive CSF1R gene (germline mutation), and cytokine receptor-like factor 2(CRLF2) gene rearrangement showed a 65% positive rate with FISH (Figure 1).
Dynamic changes following the infusion of anti-CD22 and -CD19 cells within 25 days: (A) IL-6 reached peak level on day 17 and returned to normal on day 20 after infusion. IL-10 level was basically normal in the whole course; (B) C-reactive protein rapidly decreased from 92mg/mL to normal, then increased to 44.2 mg/mL on day 15; (C) During the first 15 days, BNP gradually increased to peak level; (D) Expansion of anti-CD22 and anti-CD19 CAR T cells in the peripheral blood after infusion. Genomic DNA copies increased to peak level on day 15.
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T cells, the levels of IL-6 and PRO-BNP increased rapidly (Figure 2) with peak levels on days 10 and 12, respectively. The CRS response level was ranked grade 2 based on the University of Pennsylvania grading system. Copies of anti-CD22 and anti-CD19 CAR DNA quickly increased in the blood (Figure 2).
Morphological CR status and number of lymphoblasts in the bone marrow at different times. Autologous anti-CD19 CAR T cells bridging with allo-HSCT post CR3. CR4 was obtained followed by sequential of infusion donor-derived anti-CD22 and -CD19 CAR T cells.
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One month after the infusion, the patient was re-examined and the bone marrow was CR4 and MRD was negative (Figure 3).