Acute Lymphoblastic Leukemia(B-ALL)-01

Diagnosed with acute B-cell lymphoblastic leukemia on November 28, 2017.

Treatment with VDLP regimen initially, achieving partial bone marrow remission (details not reported).

February 2018: Switched to VLCAM regimen. Bone marrow flow cytometry showed 60.13% malignant immature B cells.

March 2018: Enrolled in BiTE clinical trial. Morphological remission in bone marrow, no malignant immature cells detected by flow cytometry.

May 8, 2018: Received TBI/CY+VP16 conditioning regimen followed by allogeneic stem cell transplant from fully matched sibling (AB+ donor to A+ recipient). Neutrophil recovery on day +11, megakaryocyte recovery on day +12.

December 5, 2018: Complete morphological remission in bone marrow, no malignant immature cells detected by flow cytometry. Received donor lymphocyte infusion (DLI) and prophylactic treatment with dasatinib and imatinib to prevent relapse.

February 2, 2019: Morphology showed 6.5% immature cells, flow cytometry showed 0.08% malignant immature B lymphoblasts. Received DLI therapy. March 28, 2019: Flow cytometry showed no abnormalities.

August 11, 2019: Bone marrow relapse, treated with dasatinib.

September 2, 2019: Morphology showed 3% immature cells, flow cytometry showed 0.04% malignant immature cells. Continued treatment with dasatinib, followed by 2 cycles of methotrexate chemotherapy.

May 11, 2020: Bone marrow relapse again.

Received 2 autologous CD19-CAR-T cell therapies and 2 allogeneic CD19-CAR-T cell therapies in 2020, none achieved remission.

October 26, 2020: Admitted to our hospital.

Laboratory Findings:

Blood routine: WBC 22.75 x 10^9/L, HGB 132 g/L, PLT 36 x 10^9/L

Peripheral blood immature cells: 63%

Bone marrow morphology: Hypercellular (grade II), 96% immature lymphoblasts.

Immunophenotyping: Cells express CD19, cCD79a, CD38dim, CD10bri, CD34, CD81dim, CD24, HLA-DR, TDT, CD22, CD72; partial expression of CD123. Identified as malignant immature B lymphoblasts.

Blood tumor mutation: Negative.

Leukemia fusion gene: NUP214-ABL1 fusion gene positive.

Chromosome analysis: 46, XX, t(1;9)(p34;p24), add(11)(q23)[4]/46, XX, t(1;9)(p34;p24), add(11)(q23)x2 [2]/46, XX[3]

Chimerism: Donor-derived cells account for 7.71%.

Treatment:

- VDS, DEX, LASP chemotherapy regimen administered.

- November 20: Peripheral blood immature cells 0%.

- Collection of autologous peripheral blood lymphocytes for CD19/22 dual CAR-T cell culture.

- November 29: FC regimen chemotherapy (Flu 50mg x 3, CTX 0.4g x 3).

- December 2 (prior to CAR-T cell infusion):

  - Blood routine: WBC 0.44 x 10^9/L, HGB 66 g/L, PLT 33 x 10^9/L.

  - Bone marrow morphology: Hypercellular (grade IV), 68% immature lymphoblasts.

  - Quantitative assessment of NUP214-ABL1 fusion gene: 24.542%.

  - Flow cytometry: 46.31% of cells express CD38dim, CD22, BCL-2, CD19, CD10bri, CD34, CD81dim, CD24, cCD79a, indicating malignant immature B lymphoblasts.

- December 4: Infusion of autologous CD19/22 dual CAR-T cells (3 x 10^5/kg).

- CAR-T related side effects: Grade 1 CRS, fever on Day 6 with Tmax of 40°C, fever controlled by Day 10. No neurotoxicity observed.

- December 22 (Day 18 assessment): Morphological complete remission in bone marrow, no malignant immature cells detected by flow cytometry. Quantitative assessment of NUP214-ABL1 fusion gene: 0%.