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

Pediatr Blood Cancer. 2012 Jun;58(6):846-51. doi: 10.1002/pbc.24021. Epub 2011 Dec 16.

Abstract

Background: The 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.

Procedure: Forty-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.

Results: ABD 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).

Conclusions: The 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Disease-Free Survival
  • Gene Deletion
  • Genes, T-Cell Receptor gamma / genetics*
  • Humans
  • Immunophenotyping
  • Induction Chemotherapy
  • Kaplan-Meier Estimate
  • Polymerase Chain Reaction
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Prognosis
  • Proportional Hazards Models
  • Real-Time Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Treatment Outcome

Substances

  • Receptors, Antigen, T-Cell, gamma-delta