A 72-year-old male was admitted with cervical lymph node enlargement for more than 1 month. No remarkable findings were noted in the patient’s medical history. Physical examination revealed several enlarged bilateral lymph nodes in the neck and supraclavicular fossae. No enlarged lymph nodes were palpable at other sites. The liver and spleen were not palpable under the lower edge of the ribs. The complete blood count was as follows: white blood cells, 4.88 × 109/L; hemoglobin, 129 g/L; platelets, 171 × 109/L; peripheral blood smear, normal leukocyte sorting; and metabolic panel, normal. Computed tomography (CT) scans revealed multiple enlarged lymph nodes in the neck. No enlarged lymph nodes were observed in the mediastinum, pelvic cavity, or bilateral groin.
The patient underwent neck lymphadenectomy, and two lymph nodes were completely resected. The enlarged lymph nodes that were resected were about 2.0 cm × 2.0 cm, and 1.0 cm × 1.0 cm in size. The pathological specimen of the lymph nodes revealed normal lymph node structure, abnormal lymphocyte diffuse proliferation, infiltration of the capsule and surrounding soft tissue by abnormal lymphocytes, medium cell volume, scant cytoplasm, round or irregular nuclei, meticulous nuclear chromatin, and visible nucleoli. Immunohistochemical staining revealed that the tumor cells were positive for CD3, CD5, CD99, TdT, CD4, CD8, PAX5, CD1a, and CD117. The Ki67 positivity rate was approximately 70%. Flow cytometry immunophenotypic analysis revealed that an abnormal population of lymphoblasts comprised of approximately 82.95% mononuclear cells were positive for cCD3, CD7, CD38, CD2, CD99, and CD45RA; partially expressed CD4, CD8, TdT, and CD1a; weakly expressed CD5; and did not express mCD3, CD10, CD16, CD56, CD57, CD25, CD26, CD30, CD45RO, or CD34.
Morphological biopsy and cytochemical analyses of the BM showed no abnormal cells. The karyotype was normal at 46, XY (20). Flow cytometry immunophenotypic analysis revealed 9.81% aberrant T lymphocytes in the mononuclear cells of the bone marrow, which were strongly positive for cCD3 and CD7; positive for CD11b, CD48, and CD45RA; and negative for CD34, TDT, HLADR, CD1a, CD99, mCD3, CD8, CD10, CD56, CD16, CD94, Perforin, CD57, CD45RO, CD30, PD-1, and other myeloid and B lineage markers.
The patient then received initial inductive treatment; the low-intensity mini-hyper-CVD (C:CTX, cyclophosphamide, V:VCR, vincristine, D:DXM, dexamethasone) [4] was optimized by combination with venetoclax, which was administered at a dose of 100 mg on days 1–2 and 200 mg on days 3–14.
After 8 days, the results of the initial bone marrow specimens for fusion gene screening at the RNA level by whole-transcriptome RNA sequencing detected BCR-ABL1 gene fusion. The lymph node specimen was tested by fluorescence in situ hybridization (FISH) using a probe specific for BCR-ABL1 rearrangement; the percentage of the positive signal was 74% (Fig. 1). Together with BCR-ABL1 rearrangement, real-time polymerase chain reaction (RT-PCR) revealed a fusion transcript of e1a2 BCR-ABL1 that encodes the 190 kDa BCR-ABL1 protein (BCR-ABL1/ABL1, 35.13%).
Based on the above findings, the patient was diagnosed with T-LBL (Ann Arbor stage IVA) with BCR-ABL1 (P190) fusion transcript; tyrosine kinase inhibitor (TKI) was not added to the initial inductive treatment because the treatment was initiated prior to obtaining the final results.
Two weeks following induction therapy, flow cytometric immunophenotypic analysis of BM cells revealed measurable residual disease, and RT-PCR revealed BCR-ABL1 rearrangement in 2.71% of cells. Moreover, the patient underwent central nervous system prophylaxis with intrathecal therapy four times (three drug combinations: methotrexate, cytarabine, and dexamethasone). The consolidated chemotherapy regimen consisted of low-intensity methotrexate (MTX) + cytarabine (Ara-C) in combination with imatinib (400 mg qd) after day 8. The following were also administered: 2 mg VCR on day 7, 60 mg prednisone on days 7–13, and 400 mg qd imatinib beginning on day 8. Two weeks following the second therapeutic regimen, RT-PCR revealed BCR-ABL1 rearrangement in 0.76% of BM cells. The consolidated chemotherapeutic regimens were revised to COP (CTX + vincristine + prednisone) + TKI every month, and imatinib was replaced with flumatinib because the patient developed edema in both lower limbs (1.2 g CTX on day 1, 2 mg VCR on day 1, 60 mg prednisone on days 1–7, and 0.6 g flumatinib on day 7).
After 2 months, positron emission tomography revealed a complete metabolic response. The patient then received maintenance treatment with targeted drugs and chemotherapeutic drugs (alternating protocols A and B every 28 days). Protocol A included 400 mg venetoclax on days 1–7 and 600 mg flumatinib once daily on days 1–14, while Protocol B included 600 mg flumatinib on days 1–14, 50 mg 6-mercaptopurine orally on days 15–21, and 20 mg methotrexate orally once daily on day 22. RT-PCR results for BCR-ABL1 rearrangement in peripheral blood during consolidation therapy every 3 months revealed values of 0.12%, 0.13%, 0.01%, 0.04%, respectively, and positron emission tomography revealed a complete metabolic response after 4 and 15 months of therapy.