A New Treatment Strategy for Early T-Cell Precursor Acute Lymphoblastic Leukemia: A Case Report and Literature Review

Abstract

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive and extremely fatal subtype of T-cell acute lymphoblastic leukemia (T-ALL), characterized by the similar transcriptional and immunophenotypic profiles to those of early T-cell precursors and positive expressions of myeloid antigens. Besides, the gene expression profile in ETP-ALL is similar to that in myeloid malignancies. The clinical characteristics, treatments and prognoses of ETP-ALL are significantly heterogeneous. In the present study, we reported a 43-year-old female patient who lacked terminal deoxynucleotidyl transferase (TDT) expression in immunophenotype and displayed mutations of fms-like tyrosine kinase-internal tandem duplication (FLT3-ITD), paired-box domain 5 (PAX5) and SH2B adaptor protein 3 (SH2B3) (PAX5 and SH2B3, the genes critical to B cell identity and function), which represent myeloid and precursor B-lineage associated gene mutations, respectively. It was a rare T-ALL or T-lineage case. Because of multiple poor prognostic factors in this case, conventional induction regimens, like hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone), were invalid. The patient showed inadequate response, suggesting that this treatment was not employed on the basis of the immunophenotype. FLAG-IDA regimen (fludarabine, cytarabine [Ara-C], granulocyte-colony stimulating factor [G-CSF] and idarubicin), which is usually applied to eliminate leukemia cells, was administered combining with sorafenib as an effective induction chemotherapy. The case achieved long-term survival following the allogeneic hematopoietic stem cell transplantation (allo-HSCT). We recommend that adult ETP-ALL patients can be treated with a myeloid-oriented chemotherapy (as frontline induction treatment) along with gene-targeting inhibitors, followed by allo-HSCT.

Keywords: FLAG-IDA; PAX5; TDT; early T-cell precursor acute lymphoblastic leukemia.

Figure 1

Cellular morphology of bone marrow aspirate smear and chromosome karyotypes. (A, B) Bone marrow smear showing a proliferation of blasts (Giemsa-Wright stain). (A, B) The blasts exhibited medium sizes, round, round-like or irregularly shape, the cytoplasm were less with trailing and burr-like changes (100 × oil immersion). (C) The cytochemiscal staining was negative for POX (peroxidase). (D) Chromosome analysis demonstrated + 4 (arrow) in 4 of 10 metaphases examined.

Figure 2

Immunophenotypic analysis of the blasts cells exhibited ETP-ALL. Through the flow cytometry analysis, blast cells were gated and showed in blue (P3). Normal mature lymphocytes were showed in green for comparison (P2). The immunophenotype of blasts were CD7, CD117, CD34, CD33, CD38, CD3 (dim), cytoplasmic CD3, and negative for TDT, CD123, CD36, HLA-DR, CD64, CD11b, CD13, CD16, CD14, CD15, CD64, CD11c, CD4, CD5, CD8, CD10, CD19, lambda, kappa, CD20, CD22, MPO, CD1a, CD99, CD2. The phenotype was consistent with early T-cell precursor acute lymphoblastic leukemia (ETP-ALL).