Acute Lymphoblastic Leukemia(T-ALL)-02

Clinical Features:

- Diagnosis: Acute T-cell lymphoblastic leukemia

- Onset: Late March 2018

- Initial symptoms: Multiple superficial lymph node enlargement throughout the body

- Initial blood routine: WBC: 39.46*10^9/L, Hb: 129g/L, PLT: 77*10^9/L

- Bone marrow morphology: 92% blasts

-Flow cytometry: 95.3% abnormal cells expressing 

TdT+CD99+CyCD3+CD7stCd5DdimCD4-CD8-mCD3-CD45dim

- Fusion genes: Negative

- Gene mutation: NOTCH1 gene mutation detected

- Chromosome analysis: Normal karyotype

Treatment History:

- April 3, 2018: Induction therapy with VDCP regimen

- April 18, 2018: Bone marrow blasts comprised 96%

- April 20, 2018: Achieved remission after CAG regimen

- May 18, 2018: Consolidation therapy with CMG+VP regimen

- June 22, 2018: Bone marrow blasts increased to 40%, relapse of leukemia

- July 25, 2018: CLAM regimen (clarithromycin+cyclophosphamide+amikacin)

- Hematopoietic stem cell transplantation from HLA-matched sibling using FLU+BU conditioning on August 14

- Monitoring post-transplant: Remission of bone marrow morphology at 1 month, 3 months, 6 months, 9 months, and 11 months

- Bone marrow morphology showed remission at 16 months post-transplant, with flow cytometry revealing 0.02% malignant immature lymphocytes

- November 13, 2020: Peripheral blood chimerism from donor source was 97.9%

- Peripheral blood primitive cells: 20%

- December 18, 2020: Bone marrow morphology: 60.6% blasts

- Flow cytometry: 30.85% malignant immature T lymphocytes

- Chromosome analysis: 46, XY (20)

- Received DA regimen chemotherapy on January 19, 2021

- Bone marrow morphology on January 19, 2021: Grade III hyperplasia, 16% blasts

- Chromosome karyotype analysis: 46, XY (20)

- Flow cytometry: 7.27% of cells (among nuclear cells) expressed CD99bri, CD13, CD38, cbcl-2, cCD3, HLA-ABC bri, CD7bri, and partially expressed CD5dim, indicating malignant immature T lymphocytes

- Leukemia fusion gene screening: Negative

- Blood tumor mutation analysis (86 types):

  1. PHF6 K299Efs*13 mutation positive

  2. RUNX1 S322* mutation positive

  3. FBXW7 E471G mutation positive

  4. JAK3 M511I mutation positive

  5. NOTCH1 Q2393* mutation positive

Treatment:

- January 22: Collection and culture of autologous peripheral blood lymphocytes for CD7-CART

- Prior to CD7-CART infusion, patient received VLP (vincristine, l-asparaginase, prednisone) plus bortezomib chemotherapy.

- February 3: FC regimen chemotherapy (Flu 50mg for 3 days + CTX 0.45g for 3 days)

- February 5 (pre-infusion): Bone marrow morphology showed 23% blasts.

- Flow cytometry revealed 4.05% cells expressing CD99bri, CD5dim, CD7bri, TDT, cCD3, indicating malignant immature T lymphocytes.

- Chromosome analysis: 46, XY (20)

- Chimerism analysis (post-HSCT): Donor-derived cells accounted for 52.19%.

- February 7: Infusion of autologous CD7-CART cells at a dose of 5*10^5/kg.

- February 15: Peripheral blood immature cells reduced to 2%.

- February 19 (Day 12 post-infusion): Patient developed fever, which lasted for 5 days before temperature control was achieved.

- March 2: Bone marrow assessment showed complete morphological remission, with flow cytometry not detecting malignant immature cells.