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.

Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick

“…Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) was first described in a cohort of pediatric patients as a distinct subgroup of T-ALL, based on a peculiar gene expression profile (GEP) and immunophenotypic characteristics [ 1 ]. ETP-ALL accounts for approximately 16% of childhood and 22% of adult T-ALL, and is generally associated with high genomic instability, poor outcomes and refractoriness to standard chemotherapy [ 2 , 3 ]. However, recent evidence shows few differences in terms of survival and prognostic significance compared to T-ALL [ 4 ].…”

Emerging Necessity of Myeloid Mutational Analysis in Early T-cell Precursor Acute Lymphoblastic Leukemia/Lymphoma (ETP-ALL)

“…Despite the significant recent advances in our understanding of the genetic background of ETP-ALL, the optimal treatment regimen remains uncertain. ETP-ALL is a rare entity accounting for approximately 16% of childhood and 22% of all adult T-ALLs [ 5 , 6 ]. That rarity, combined with the fact that it is still a relatively newly described entity, has resulted in a lack of large-scale investigational studies exploring the optimal therapeutic approach.…”