Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

Abstract

BackgroundThe absence of biallelic TCRγ deletion (ABD) is a characteristic of early thymocyte precursors before V(D)J recombination. The ABD was reported to predict early treatment failure in T‐cell acute lymphoblastic leukemia (ALL). This study aimed to investigate its prognostic value in Taiwanese patients with T‐cell ALL.ProcedureForty‐five children with T‐cell ALL were enrolled from six medical centers in Taiwan. Quantitative DNA polymerase chain reaction (Q‐PCR) was performed to check the status of TCRγ deletion. The threshold for homozygous deletions by Q‐PCR was defined as a fold‐change <0.35.ResultsABD was found in 20 patients [20:45] who had higher incidences of induction failure than those without ABD (P = 0.03; hazard ratio [HR] = 8.13; 95% confidence interval [95% CI] = 1.23–53.77) after multivariate regression analysis. Patents with ABD also had inferior EFS and OS (P = 0.071 and 0.0196, respectively). Multivariate Cox analysis indicated that the association between ABD and overall survival was independent of age and leukocyte count on presentation (P = 0.036; HR = 4.25; 95% CI = 1.10–16.42).ConclusionsThe absence of TCRγ deletion is a predictor of a poor response to induction chemotherapy for pediatric patients with T‐cell ALL in Taiwan. Providing patients with T‐cell ALL and ABD with alternative regimens may be worthwhile to test in future clinical trials. Pediatr Blood Cancer 2012; 58: 846–851. © 2011 Wiley Periodicals, Inc.

Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors

“…24,25 In the study of Gutierrez and co-workers, ABD T-ALL was associated with a poor response to induction chemotherapy, 5-year event-free survival and overall survival in pediatric T-ALL patients who were treated using the COG P9404 or DFCI 00-01 protocol. 12 Similar results were described for ABD T-ALL in children treated on Taiwanese TPOG-ALL-97/2002 protocols, 26 as well as for pediatric T-cell lymphoblastic lymphoma patients. 27 In the present study, we investigated the extent to which ETP-ALL, immature cluster T-ALL and ABD overlap by comparing gene expression and immunophenotypic profiles of the ETP-ALL and immature cluster cases and determining the ABD status of these cases.…”

“…11 As the COALL-97 protocol is a high-dose cytarabine-containing treatment, this may be one of the reasons for the relatively good outcome of ETP-ALL and ABD patients in this study compared to other studies. 10,12,19,26 However, we could not demonstrate differential sensitivity levels to various drugs including cytarabine for ETP-ALL patients in our in vitro cytotoxicity assay (Online Supplementary Figure S6). …”

Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia

“…33 Absence of a bi-allelic TCRG deletion, a molecular marker linked with a very early block in T-cell differentiation, has been associated with poor response to induction therapy and dismal 5-year event-free and overall survival in pediatric T-ALL patients treated on COG P9404 or DFCI 00-01 protocols. 12 More recently, the prognostic relevance of ABD was confirmed in pediatric T-ALL patients treated according to the Taiwan Pediatric Oncology Group protocols 34 and pediatric T-cell lymphoblastic lymphoma patients treated following a Berlin-FrankfurtMunich ALL-type strategy. 35 In our patient series, ABD was identified in about half of adult T-ALL samples and found to confer with poor overall survival.…”

Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities

“…Absence of biallelic T‐cell receptor gene gamma ( TRG ) locus deletion (ABD), which is characteristic for early thymocyte precursors before V(D)J recombination, correlates statistically significantly with the failure of induction chemotherapy of paediatric T‐ALL patients, but also poorer overall outcomes (Gutierrez et al , ; Yang et al , ). For paediatric T‐LBL, ABD was observed in a small subgroup of 4 out of 54 patients (7%) treated according to NHL‐BFM 95 or EURO‐LB 02 regimen (Callens et al , ).…”