FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-T Cells
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...
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| Format: | Article |
| Language: | English |
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Mattioli1885
2024-02-01
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| Series: | Mediterranean Journal of Hematology and Infectious Diseases |
| Subjects: | |
| Online Access: | https://www.mjhid.org/mjhid/article/view/5622 |
| _version_ | 1797205681242112000 |
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| author | Eugenio Galli Filippo Frioni Tanja Malara Enrico Attardi Silvia Bellesi Stefan Hohaus Simona Sica Federica Sorà Patrizia Chiusolo |
| author_facet | Eugenio Galli Filippo Frioni Tanja Malara Enrico Attardi Silvia Bellesi Stefan Hohaus Simona Sica Federica Sorà Patrizia Chiusolo |
| author_sort | Eugenio Galli |
| collection | DOAJ |
| description |
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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| first_indexed | 2024-03-07T13:57:46Z |
| format | Article |
| id | doaj.art-0618266f92e243388cbaa557696e5ecc |
| institution | Directory Open Access Journal |
| issn | 2035-3006 |
| language | English |
| last_indexed | 2024-04-24T08:54:59Z |
| publishDate | 2024-02-01 |
| publisher | Mattioli1885 |
| record_format | Article |
| series | Mediterranean Journal of Hematology and Infectious Diseases |
| spelling | doaj.art-0618266f92e243388cbaa557696e5ecc2024-04-16T07:59:18ZengMattioli1885Mediterranean Journal of Hematology and Infectious Diseases2035-30062024-02-0116110.4084/MJHID.2024.029FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-T CellsEugenio Galli0https://orcid.org/0000-0002-2839-916XFilippo Frioni1Tanja Malara2Enrico Attardi3Silvia Bellesi4Stefan Hohaus5Simona Sica6Federica Sorà7Patrizia Chiusolo8Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, RomeSezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, RomeDipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, RomeDipartimento di Oncoematologia, Fondazione PTV Policlinico Tor Vergata, RomeDipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, RomeSezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, RomeSezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, RomeSezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, RomeSezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Rome 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. https://www.mjhid.org/mjhid/article/view/5622Therapy-related leukemiaCAR-T cellsB-cell non-Hodgkin's lymphomaFLT3-ITD |
| spellingShingle | Eugenio Galli Filippo Frioni Tanja Malara Enrico Attardi Silvia Bellesi Stefan Hohaus Simona Sica Federica Sorà Patrizia Chiusolo FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-T Cells Mediterranean Journal of Hematology and Infectious Diseases Therapy-related leukemia CAR-T cells B-cell non-Hodgkin's lymphoma FLT3-ITD |
| title | FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-T Cells |
| title_full | FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-T Cells |
| title_fullStr | FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-T Cells |
| title_full_unstemmed | FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-T Cells |
| title_short | FLT3 Mutated Acute Myeloid Leukemia after CD19 CAR-T Cells |
| title_sort | flt3 mutated acute myeloid leukemia after cd19 car t cells |
| topic | Therapy-related leukemia CAR-T cells B-cell non-Hodgkin's lymphoma FLT3-ITD |
| url | https://www.mjhid.org/mjhid/article/view/5622 |
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