Acute Lymphoblastic Leukemia(T-ALL)-01

Clinical features:

- Diagnosis: T-cell lymphoblastic lymphoma/leukemia

- March 2020: Presented with paroxysmal cough and mediastinal mass, confirmed T-cell lymphoblastic lymphoma by mediastinal mass puncture biopsy.

- Received 8 cycles of chemotherapy and over 20 sessions of radiotherapy, resulting in significant reduction of mediastinal mass.

- January 16, 2021: Developed pain in the right lower limb.

- Blood routine: WBC 122.29 x 10^9/L, HGB 91 g/L, PLT 51 x 10^9/L

- Bone marrow morphology: 95.5% primitive lymphoblasts.

- Bone marrow flow cytometry: 91.77% of cells were immature T-cell lymphoblasts.

- Genetic sequencing: Mutations in NOTCH1, IL7R, ASXL2 genes detected.

- Received Hyper-CVAD/B regimen, ESHAP regimen subsequently, both ineffective with persistent fever.

- February 18, 2021: Admitted to our hospital.

- Presented with fever, chest CT showed pneumonia.

- Blood routine: WBC 2.89 x 10^9/L, HGB 57.7 g/L, PLT 14.9 x 10^9/L

- Peripheral blood immature cells: 90%

- Bone marrow morphology: Hypercellular (IV grade), 85% primitive lymphoblasts.

- Immunophenotyping: 87.27% of cells were malignant primitive T-cell lymphoblasts.

- Chromosomal analysis: 46,XX [24]; three additional abnormal karyotypes observed.

- Mutated genes:

  1. IL7R T244_I245insARCPL mutation positive

  2. NOTCH1 E1583_Q1584dup mutation positive

  3. ASXL2 Q602R mutation positive

- Leukemia fusion gene screening: Negative

- PET/CT results: No significant hypermetabolic tumor foci in the entire skeleton and bone marrow cavity.

Treatment:

- Started VP regimen chemotherapy, detailed as follows: Vincristine (VDS) 3mg once, Dexamethasone (Dex) 7mg every 12 hours for 9 days, along with anti-infective treatment.

- March 1: Peripheral blood immature cells reduced to 7%.

- March 4: Collected autologous lymphocytes for CD7-CAR T cell culture.

- March 8: Started VLP regimen combined with Sida benzamine treatment.

- March 14: Received FC regimen chemotherapy (Fludarabine 0.35g for 3 days, Cyclophosphamide 45mg for 3 days).

- March 17 (pre-cell infusion):

  - Bone marrow residual immunophenotyping: 15.14% cells express CD7 bright, CD3 dim, cytoplasmic CD3, T cell receptor restricted delta (TCRrd), partial expression of CD99, indicating malignant primitive T cells.

- March 19: Infused autologous CD7-CAR T cells (1 x 10^6/kg).

- CAR-T related side effects: Grade 1 CRS (fever), no neurotoxicity.

- April 6 (Day 17): Bone marrow morphology showed remission, flow cytometry did not detect malignant primitive cells.