FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-T Cells

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Eugenio Galli https://orcid.org/0000-0002-2839-916X
Filippo Frioni
Tanja Malara
Enrico Attardi
Silvia Bellesi
Stefan Hohaus
Simona Sica
Federica Sorà
Patrizia Chiusolo


Therapy-related leukemia, CAR-T cells, B-cell non-Hodgkin's lymphoma, FLT3-ITD


Chimeric Antigen Receptor T-cells have improved the life expectancy of severely pretreated patients with aggressive hematological cancers; for this reason, therapy-related myeloid leukemias are becoming of great concern in this field, despite their clonal phylogenesis and mutational landscape have not been fully explored yet. This case discusses a 33-year-old man with refractory large B-cell lymphoma, treated with Chimeric Antigen Receptor T-cell (CAR-T) therapy as the 7th line of treatment. Despite a persistent partial response, the patient developed therapy-related acute myeloid leukemia (t-AML) six months post-CAR-T, revealing pre-existing clonal hematopoiesis. The myeloid malignancy exhibited an unusual hypocellular/dysplastic pattern, progressing to an established blast phase with cytopenia. Treatment with demethylating agents and BCL2 inhibitors proved ineffective, leading to t-AML with hyperleukocytosis and FLT3-ITD gain, resulting in the patient's death. This case underscores the impact of severe pretreatment and bone marrow impairment in CAR-T-associated t-AML, emphasizing their role over insertional mutagenesis. Furthermore, it highlights the retention of classic therapy-related leukemia characteristics, including the potential for acquiring FLT3 mutations and displaying dysplastic morphology in these secondary leukemias.


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1. Miller PG, Sperling AS, Brea EJ, et al. Clonal hematopoiesis in patients receiving chimeric antigen receptor T-cell therapy. Blood Adv. 2021;5(15):2982-2986. doi:10.1182/BLOODADVANCES.2021004554
2. Teipel R, Kroschinsky F, Kramer M, et al. Prevalence and variation of CHIP in patients with aggressive lymphomas undergoing CD19-directed CAR T-cell treatment. Blood Adv. 2022;6(6):1941-1946. doi:10.1182/BLOODADVANCES.2021005747
3. Strati P, Varma A, Adkins S, et al. Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma. Haematologica. 2021;106(10):2667-2672. doi:10.3324/HAEMATOL.2020.254045
4. Alkhateeb HB, Mohty R, Greipp P, et al. Therapy-related myeloid neoplasms following chimeric antigen receptor T-cell therapy for Non-Hodgkin Lymphoma. Blood Cancer Journal 2022 12:7. 2022;12(7):1-5. doi:10.1038/s41408-022-00707-4
5. Cordeiro A, Bezerra ED, Hirayama A V., et al. Late Events after Treatment with CD19-Targeted Chimeric Antigen Receptor Modified T Cells. Biol Blood Marrow Transplant. 2020;26(1):26-33. doi:10.1016/J.BBMT.2019.08.003
6. Fianchi L, Pagano L, Piciocchi A, et al. Characteristics and outcome of therapy-related myeloid neoplasms: Report from the Italian network on secondary leukemias. Am J Hematol. 2015;90(5):E80-E85. doi:10.1002/AJH.23966
7. Kayser S, Döhner K, Krauter J, et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood. 2011;117(7):2137-2145. doi:10.1182/BLOOD-2010-08-301713