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. 2013;35(5):337-42.
doi: 10.5581/1516-8484.20130115.

Gene rearrangement study for minimal residual disease monitoring in children with acute lymphocytic leukemia

Juliana Godoy Assumpção  1 , Francisco Danilo Ferreira Paula, Sandra Guerra Xavier, Mitiko Murao, Joaquim Caetano de Aguirre Neto, Alvaro Pimenta Dutra, Eduardo Ribeiro Lima, Benigna Maria de Oliveira, Marcos Borato Viana
Affiliations

Gene rearrangement study for minimal residual disease monitoring in children with acute lymphocytic leukemia

Juliana Godoy Assumpção et al. Rev Bras Hematol Hemoter. 2013.

Abstract

Objective: To detect markers for minimal residual disease monitoring based on conventional polymerase chain reaction for immunoglobulin, T-cell receptor rearrangements and the Sil-Tal1 deletion in patients with acute lymphocytic leukemia.

Methods: Fifty-nine children with acute lymphocytic leukemia from three institutions in Minas Gerais, Brazil, were prospectively studied. Clonal rearrangements were detected by polymerase chain reaction followed by homo/heteroduplex clonality analysis in DNA samples from diagnostic bone marrow. Follow-up samples were collected on Days 14 and 28-35 of the induction phase. The Kaplan-Meier and multivariate Cox methods were used for survival analysis.

Results: Immunoglobulin/T-cell receptor rearrangements were not detected in 5/55 children screened (9.0%). For precursor-B acute lymphocytic leukemia, the most frequent rearrangement was IgH (72.7%), then TCRG (61.4%), and TCRD and IgK (47.7%); for T-acute lymphocytic leukemia, TCRG (80.0%), and TCRD and Sil-Tal deletion (20.0%) were the most common. Minimal residual disease was detected in 35% of the cases on Day 14 and in 22.5% on Day 28-35. Minimal residual disease on Day 28-35, T-acute lymphocytic leukemia, and leukocyte count above 50 x 10(9)/L at diagnosis were bad prognostic factors for leukemia-free survival in univariate analysis. Relapse risk for minimal residual disease positive relative to minimal residual disease negative children was 8.5 times higher (95% confidence interval: 1.02-70.7).

Conclusion: Immunoglobulin/T-cell receptor rearrangement frequencies were similar to those reported before. Minimal residual disease is an independent prognostic factor for leukemia-free survival, even when based on a non-quantitative technique, but longer follow-ups are needed.

Keywords: Gene rearrangement; Neoplasm, residual; Polymerase chain reaction; Precursor cell lymphoblastic leukemia-lymphoma.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interest

Figures

Figure 1
Figure 1
A: Leukemia-free survival for all patients (n = 57); B: Leukemia-free survival for patients with positive (n = 9) or negative (n = 31) minimal residual disease (MRD).
See this image and copyright information in PMC

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