Early T-Cell Precursor Acute Lymphoblastic Leukemia: Diagnosis, Updates in Molecular Pathogenesis, Management, and Novel Therapies

Abstract

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinct subtype of T lymphoblastic leukemia (T-ALL) identified in 2009, due to its unique immunophenotypic and genomic profile. The outcome of patients was poor in earlier studies, and they were prone to have induction failure, with more frequent relapse/refractory disease. Recent advances had been made in discoveries of genetic aberrations and molecular pathogenesis of ETP-ALL. However, the diagnosis and management of ETP-ALL is still challenging. There are limited choices of novel therapies so far. In this review article, it highlighted the diagnostic issue of ETP-ALL, pitfall in diagnosis, and strategy of accurate diagnosis. The review also summarized current understanding of molecular mechanism of leukemogenesis. The emerging role of risk-adapted therapy and allogenic stem cell transplant in optimizing the outcome of patients with ETP-ALL was discussed. Finally, some potential novel therapies were proposed based on the current understanding of molecular pathogenesis.

Near-Early T-Cell ALL with Overexpression of BAALC and BCL-2 Genes, Non-Responsive to High-Dose Chemotherapy and Hematopoietic Stem Cell Transplantation, but with Impressive Response to Venetoclax

“…CD19-, cytCD3+, MPO-, cytCD79a-. Taking into account unequivocal CD5 positivity of blast cells proven by immunohistochemistry, these findings were considered consistent with diagnosis of near-early T-ALL [6,7]. Cytogenetic analysis (22.04.21) revealed hyperdiploid in half out of 20 analyzed metaphases with the following karyotype: 2n=50-52, XX, +8, +10, +11, +14.…”

“…T-cell acute lymphoblastic leukemia in adults is considered to be rare disease with inferior response linked with BAALC-overexpression and complex karyotypes with ≥3 cytogenetic alterations per metaphase [1,2]. Meanwhile, there is evidence, that early variant of T-ALL is characterized by high expression of gene BCL-2 and, hence, can be treated successfully with venetoclax [3][4][5][6][7]. It has been also shown, that T-ALL patients with higher levels of BAALC expression are more likely to have early T-ALL (P<0.0001) and CD34 positivity (P<0.0001).…”

“…Fouryear OS and EFS rates in patients with increased vs normal level of BAALC expression, were 18% vs 58% (P=0.0001) and 21% vs 85%) (P=0.0008), respectively [1]. Recent data show that all abovementioned clinical and laboratory parameters are greatly improved in a case of high-dose risk chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT), which was performed in remission [6,7].…”

Case Report: Spontaneous remission of early T-cell precursor acute lymphoblastic leukemia

“…The prognosis with these patients was poor in previous studies because they were susceptible to induction failure, with more frequent relapse/refracture disease. 15 This may explain the relatively short time to relapse. Reports of spontaneous remissions of ALL have shown periods of temporary remission varying in duration from 14 days to 8 years.…”

Comparison of characteristics and outcomes on ETP-ALL/LBL and non-ETP ALL patients receiving allogeneic hematopoietic stem cell transplantation

“…Early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a special subtype of T-ALL first recognized in 2009 (2), which is characterized by arrested early T-cell differentiation, with some myeloid and stem cell characteristics remaining at the immunophenotypic and also genetic levels (3,4). The incidence of ETP-ALL reported in previous studies is 11%-16% of T-ALL cases in children and 7.4%-32% in adults (5)(6)(7), respectively. In a large cohort study in Chinese adult T-ALL (n = 112), ETP-ALL accounts for 47.3% of all patients (8).…”