Acute Lymphoblastic Leukemia(B-ALL)-03

Case Features:

- Diagnosed with acute B-cell lymphoblastic leukemia at the end of May 2020.

- Blood routine: WBC 5.14x10^9/L, HGB 101.60g/L, PLT 6x10^9/L.

- Bone marrow morphology: Hypocellular with 67% primitive lymphocytes.

- Flow cytometry: 82.28% of cells express CD38, HLA-DR, CD19, CD10, CD105, TDT, CD22, cCD79a, partially express CD9, weakly express CD13.

- Fusion gene screening negative; WT1 57.3%; no PH-like ALL-related fusion genes detected.

- FISH: TP53 mutation positive.

- Chromosomes: 63-58, XXY, +Y, +1, +del(1)(q41q42), -2, -3, +6, -7, +8, -9, +10, -12, -13, +14, +15, -17, +18, -20, +22(cp16)/46, XY[4].

- Received VCDLP regimen for 2 courses without remission.

- CAM-VL regimen (CTX 2gx2, Arac 200mgx6, 6-MP 100mgx14, VDS 4mgx2, L-ASP 10,000 IUx7) on July 22, 2020, still without remission.

- Bone marrow flow cytometry on September 25, 2020: 7.35% of cells express CD81, CD19, CD10, CD38, CD33, weakly express CD20, CD45.

- Blood tumor mutation analysis: TP53 mutation.

- Chromosomes: 46, XY[20].

- Started CD19-CART therapy.

- FC regimen (FLU 62.7mg x 4 days, CTX 1045mg x 2 days) chemotherapy.

- October 1, 2020: Autologous CD19-CART cell infusion at 4.7x10^7/kg.

- CRS grade 2 with grade 1 neurotoxicity, improved after supportive treatment.

- October 29, 2020: Complete remission in bone marrow morphology, no malignant primitive cells on flow cytometry.

- December 31, 2020: Dry cough, nausea, vomiting, generalized weakness.

- Blood routine: WBC 15.53x10^9/L, HGB 134g/L, PLT 71x10^9/L.

- Bone marrow aspiration indicating relapse.

- January 2, 2021: Admitted to our hospital.

- Blood routine: WBC 20.87x10^9/L, HGB 118.30g/L, PLT 58.60x10^9/L.

- Creatinine 134umol/L, stage 3 hypertension, medical history of 4 years.

- Peripheral blood classification: 62% primitive cells.

- Immunophenotyping: 28.48% of cells (nucleated cells) express CD10, CD38dim, HLA-DR, CD20dim, CD24, CD81, cCD79a, CD22, CD268dim, CD58, partially express CD123, TDT, do not express CD34, CD19, MPO, CD117, CD13, CD33, CD11b, clgM, CD79b, CD7, cCD3, kappa, lambda, indicating malignant primitive B lymphocytes.

- Blood tumor mutation analysis: TP53 R196P mutation positive.

Treatment:

- Received VLP chemotherapy, along with treatment for hypertension, creatinine reduction, and hydration alkalinization.

- January 19: Blood routine showed WBC 1.77x10^9/L, HGB 71g/L, PLT 29.8x10^9/L.

- Peripheral blood classification: No primitive lymphocytes.

- Bone marrow morphology: Hypercellularity (V grade), focal areas of IV grade, with 42% primitive lymphocytes.

- Flow cytometry: 13.91% of cells express CD10, cCD79a, CD38, CD81, CD22, do not express CD20, CD34, CD19, indicative of malignant primitive B cells.

- Chromosomal karyotype:

  - 35,XY,-2,-3,-4,-5,-7,-9,-12,-13,-16,-17,-20[8]/35,XY,+X,-2,-3,-4,-5,-7,-9,-10,-12,-13,-16,-17,-20[1]/36,XY,add(1)(q42),-2,-3,-4,-7,-9,-12,-13,-16,-17,-20[1]/46,XY[20].

- January 20: Lymphocytes collected for CD22-CART cell culture.

- January 21: Lumbar puncture performed, intrathecal chemotherapy administered to prevent central nervous system leukemia; cerebrospinal fluid examination showed no abnormalities.

- January 22: Received Arac, 6MP, L-ASP chemotherapy, and FC (Flu 50mg x 3, CTX 0.5g x 3) chemotherapy.

- February 7 (before infusion): Bone marrow morphology showed 93% primitive lymphocytes.

- Flow cytometry: 76.42% of cells express CD38, cCD79a, CD22, cbcl-2, CD123, CD10bri, CD24, CD81, do not express CD4, CD3, CD13+33, CD34, CD20, CD19, CD279 (PD1), CD274 (PDL1), indicative of malignant primitive B cells.

- Developed skin and soft tissue infection with fever; improved after antibiotic treatment.

- February 9: Autologous CD22-CART cell infusion (5x10^5/kg).

- CAR-T-related side effects: CRS grade 1, fever on Day 6 with Tmax 40°C, controlled temperature on Day 10; no neurotoxicity.

- March 11: Bone marrow assessment showed complete morphological remission, flow cytometry showed no malignant primitive cells.