case_images: PMC7266936_01
case_images: Therapeutic response for the anti-CLL1 CAR-T treatment. Plot of therapeutic response in this sAML during her primary diagnosis, 1st relapse and 2nd relapse including anti-CLL1 CAR-T cells therapy.
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case_images: PMC7266936_01_fonc-10-00685-g0001.jpg
case_images: F1
case_images: B-cell acute lymphoblastic leukemia (ALL) relapse. Bone marrow (BM) aspiration was performed every 2 weeks from July 2018, and blast percentage gradually increased from initial 7.5% to 19.5% within 1 month of observation (Figure 1). Initially, she was enrolled into the GD-2008-ALL clinical trial (NCT00846703) and then achieved complete remission (CR) after one course of induction therapy, while her minimal residual disease (MRD) evaluated by flow cytometry remained above 0.01% during all treatment phases (Figure 1). Due to the lack of economic support, she was treated with the HKPHOSG-Relapsed-ALL-2007 protocol and experienced persistent fever, pancytopenia, and elevated peripheral blood blast cells during the treatment (Figure 1). RUNX1R204P, and WT1S381fs mutation (Supplementary Figure 1, Supplementary Table 1). Results were double confirmed by a peer review from the Shenzhen Gene-Immune Medical Institute (GIMI). Strikingly, the morphologic CR and MRD <0.1% were sustained for ~9 months at the time of this report's submission (Figures 1-3, Supplementary Table 2).
case_images: Morphologic and immunophenotypic evolution for this secondary AML case. Morphologic (A) (upper, primary diagnosis; upper middle, 1st relapse; lower middle, 2nd relapse; and lower, post anti-CLL1 CAR T-cell therapy) and flow cytometric (B,C) features at primary diagnosis (upper panel), 1st relapse (upper middle panel), 2nd relapse (lower middle panel), and post anti-CLL1 CAR T-cell therapy (lower panel) in this secondary AML case; gating: all events (All Events) or blast and erythroid cells (Blast+E). The green, blue, orange, light blue, gray and red dots represent lymphocytes, monocytes, neutrophils, erythrocytes, debris, and blasts population, respectively.
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case_images: PMC7266936_01_fonc-10-00685-g0002.jpg
case_images: F2
case_images: From this comparison, we found that the blast cells from the second relapse sample originated from the myeloid lineage (CD34+CD38+CD10dimCD19dimCD123+CD33+CLL1+) and not from the B cell lineage (Figures 2A-C). Of note, CLL1 was highly expressed on the myeloid blast cells (Figure 3A, Supplementary Figure 2), which could be a target for CAR T-cell therapy. However, the CLL1+ cells were not completely eliminated until early in the 6 months after CAR T-cell therapy (Figure 3A, Supplementary Table 2). Strikingly, the morphologic CR and MRD <0.1% were sustained for ~9 months at the time of this report's submission (Figures 1-3, Supplementary Table 2).
case_images: MRD and CRS status during acnti-CLL1 CAR T-cell therapy. (A) CLL1 population, intensity, and the blast percentage (gating on CLL+ cells) before (upper panel) and after (lower panel) anti-CLL1 CAR T-cell therapy. The blue and red dots represent erythrocytes and blasts population, respectively. (B) Anti-CLL1 CAR T-cells persistence (upper panel), serum IL-6 level (middle panel), and temperature and therapy scheme (low panel) during the first month of anti-CLL1 CAR T- cell therapy in this secondary AML case.
case_images: fonc-10-00685-g0003.jpg
case_images: PMC7266936_01_fonc-10-00685-g0003.jpg
case_images: F3
case_images: Of note, CLL1 was highly expressed on the myeloid blast cells (Figure 3A, Supplementary Figure 2), which could be a target for CAR T-cell therapy. Following the guidelines, glucocorticoids and tocilizumab intervention were not prescribed (Figure 3B). However, the CLL1+ cells were not completely eliminated until early in the 6 months after CAR T-cell therapy (Figure 3A, Supplementary Table 2). Strikingly, the morphologic CR and MRD <0.1% were sustained for ~9 months at the time of this report's submission (Figures 1-3, Supplementary Table 2). An effective expansion was achieved in the first month, which then dropped quickly thereafter; then, a low CAR T-cell level persistence was detected 5 months after CAR T-cell injection (Figure 3B).