Clinical significance of early T‐cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children’s Cancer Study Group Study L99‐15

Abstract

Summary Early T‐cell precursor acute lymphoblastic leukaemia (ETP‐ALL) is a recently identified subtype of T‐ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT‐ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP‐ALL to a cohort of 91 patients with T‐ALL enrolled in the Tokyo Children’s Cancer Study Group L99‐15 study, which included allogeneic stem cell transplantation (allo‐SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP‐ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP‐ALL as compared with T‐ALL. The ETP‐ALL subgroup showed a significantly poorer event‐free survival (4‐year rate; 40%) than the T‐ALL subgroup (70%, P = 0·014). Of note, three of four relapsed ETP‐ALL patients survived after allo‐SCT, indicating that allo‐SCT can be effective for this drug‐resistant subtype of T‐ALL.

Redefining ALL classification: toward detecting high-risk ALL and implementing precision medicine

“…67 Many studies reported poor outcome of ETP ALL, 67,68 but this is mitigated by contemporary risk-adapted therapy. 69,70 ETP ALL is genetically heterogeneous, with mutation of multiple cellular pathways including (1) hematopoietic and lymphoid development (RUNX1, IKZF1, ETV6, GATA3, and EP300); (2) Ras, cytokine receptor, and kinase signaling (NRAS, IL7R, KRAS, JAK1, JAK3, NF1, PTPN11, and SH2B3); and (3) loss-of-function mutations targeting epigenetic regulators.…”

An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study

“…5,6 This immature cluster shows a high level of enrichment of transcripts that are associated with early thymic precursor (ETP)-ALL, 22 a subgroup of T-ALL that exhibit a stem cell/immature myeloid-like immunophenotype, resistance to treatment and poor outcome. 15,[23][24][25][26] Genomic analysis of ETP-ALL has revealed high rates of mutations in factors involved in cytokine receptor and RAS signaling, hematopoiesis and epigenetic modification, 15 but the precise molecular basis of these patients' adverse prognosis remains unclear.…”

“…25,26,39,40 It remains to be seen whether similar strategies will improve the outcome of HOXA Pos adult ETP-ALL patients. The introduction of more intensive pediatric-based regimens has been central to recent improvements in the outcome of hitherto resistant adult ALL.…”

Absence of terminal deoxynucleotidyl transferase expression identifies a subset of high-risk adult T-lymphoblastic leukemia/lymphoma

“…The ETP immunophenotype is described as lack of CD1a and CD8, CD5-/dim þ , and expression of one or more myeloid or stem cell-related antigens. 18,19 Both studies focused on pediatric patients and did not further specify whether TdTnegative T-ALL/LBL cases fall into the ETP type of T-ALL/LBL.…”