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Acute Lymphoblastic Leukemia(B-ALL)-02

Patient: Wang XX

Gender：Female

Age: 3 years old

Nationality: Chinese

Diagnosis:Acute Lymphoblastic Leukemia(B-ALL)

Case Characteristics:

- May 19, 2019: Diagnosed with acute B-cell lymphoblastic leukemia (B-ALL)

- Presented with multiple scalp masses and lymphadenopathy

- Blood routine: WBC 13.3 x 10^9/L, HGB 94 g/L, PLT 333 x 10^9/L, abnormal lymphocytes 4%

- Bone marrow morphology: 80.2% immature lymphoblasts (blasts)

- Immunophenotyping: 74.19% of cells are malignant B-lineage precursor cells expressing CD45dim, CD19, CD9, CD22, CD81, CD58, cCD79a, CD38, HLA-DR, partially expressing cIgM. Diagnosis: B-ALL (Pre-B stage)

- Fusion gene: MLL-ENL positive, Philadelphia chromosome-like (Ph-like) screen negative

- Chromosome: 46, XX, t(11;19)(q23;p13), del(20)(q12) [3]/46, XX [7]

- VDLD regimen chemotherapy initially achieved immunological remission after 1 month, MLL-ENL quantitative PCR 0.026%

- Continued chemotherapy as per pediatric protocol, MLL-ENL quantitative PCR 0 after the 4th cycle. Further chemotherapy continued.

- March 2020: Bone marrow immunological residual disease 0.35%, MLL-ENL quantitative PCR 0.53%, indicating a trend towards relapse. Family refused transplant. Continued chemotherapy for 3 cycles.

- July 2020: Bone marrow relapsed comprehensively.

- November 11, 2020: Intrathecal chemotherapy, CSF immunological residual disease 66%, diagnosed with central nervous system leukemia. Intrathecal chemotherapy repeated twice, CSF turned negative.

- December 31, 2020: Admitted to our hospital.

- Blood routine: WBC 3.99 x 10^9/L, HGB 66 g/L, PLT 57 x 10^9/L

- Peripheral blood blast count: 69%

- Bone marrow morphology: 90% immature lymphoblasts (blasts)

- Immunophenotyping: 84.07% of cells express CD38, CD19, CD81dim, cCD79a, HLA-DR, cIgM, CD22, CD123, partially express CD24, CD15dim, indicating malignant immature B lymphoblasts.

- Fusion gene: MLL-ENL fusion gene positive, quantitative PCR 44.419%

- Genetic mutation: KMT2D mutation positive (germline origin)

- Chromosome karyotype: 46, XX, del(1)(p36.1), del(1)(q31q42), del(11)(q13), t(11;19)(q23;p13.3), add(14)(q34), -17, +mar [7]/46, idem, t(3;16)(p21;p13.3) [1]/46, XX [13]

- PET-CT: Diffuse metabolic increase in the entire skeletal and bone marrow cavity, high suspicion of leukemia recurrence; splenomegaly with increased metabolism, likely involving leukemia.

- Performed lumbar puncture and intrathecal chemotherapy once, no abnormalities found in CSF-related tests.

Treatment:

- Two weeks of VLP chemotherapy, peripheral blood blasts 5% on January 18.

- January 25: Peripheral blood blasts 91%, treated with CTX, Ara-C, 6-MP chemotherapy.

- February 3: Peripheral blood blasts 22%.

- February 4: Collection of 50ml autologous peripheral blood for CD19-CART cell culture.

- MTX 1g, FC chemotherapy (Flu 15mg daily x 3 days, CTX 0.12g daily x 3 days).

- February 13 (pre-infusion): Bone marrow morphology shows 87.5% blasts, flow cytometry shows 79.4% malignant blasts.

- MLL-ENL fusion gene quantitative analysis: 42.639%.

- February 14: Infusion of CART cells at a dose of 5 x 10^5/kg.

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

- Day 20 post-infusion: Blood smear shows tumor proliferation, CART cell proportion 0.07%.

- Ineffective CART cell therapy.

- March 8, 2021: Blood routine: WBC 38.55 x 10^9/L, HGB 65g/L, PLT 71.60 x 10^9/L.

- Peripheral blood blasts: 83%. Autologous peripheral blood collected 60ml for CD19/CD22 dual CART cell culture.

- Treated with cytarabine and dexamethasone to control tumor burden.

- March 18: FC chemotherapy (Flu 15mg daily x 3 days, CTX 0.12g daily x 3 days).

- March 22 (pre-infusion): Blood routine: WBC 0.42 x 10^9/L, HGB 93.70g/L, PLT 33.6 x 10^9/L. Peripheral blood morphology: 6% blasts.

- Bone marrow morphology: 91% blasts. Residual in bone marrow: 88.61% cells expressing CD38, CD19, cCD79a, CD81, CD22, indicating malignant immature B lymphoblasts.

- MLL-ENL fusion gene quantitative analysis: 62.894%.

- Chromosome karyotype analysis: 46, XX, del(1)(p36.1), del(11)(q13), t(11;19)(q23;p13.3), add(14)(q34), -17, +mar [2]/46, XX, del(1)(p36.1), del(1)(q31q42), del(11)(q13), t(11;19)(q23;p13.3), add(14)(q34).

- March 23: Infusion of CART cells at a dose of 3 x 10^5/kg.

- March 26 onwards: Persistent high fever and subsequently developed systemic edema.

- March 29: Peripheral blood morphology: 92% blasts; elevated transaminases and bilirubin.

- April 2: Onset of seizures, treated with diazepam.

- April 2 (Day 10): Started methylprednisolone treatment for 3 days.

- CRS reaction: Grade 3, CRES: Grade 3.

- April 8 (Day 16): Bone marrow evaluation shows complete morphological remission, flow cytometry negative for malignant blasts; MLL-ENL fusion gene quantitative analysis: 0.