Haematologica, Vol 94, Issue 6, 781-789 doi:10.3324/haematol.2008.003137
Copyright © 2009 by Ferrata Storti Foundation
Carlos A. Scrideli1 ,
Juliana G. Assumpção2 ,
Mônica A. Ganazza2 ,
Marcela Araújo2 ,
Silvia R. Toledo3 ,
Maria Lúcia M. Lee3 ,
Elisabete Delbuono3 ,
Antonio S. Petrilli3 ,
Rosane P. Queiróz1 ,
Andrea Biondi4 ,
Marcos B. Viana5 ,
José A. Yunes2 ,
Silvia R. Brandalise2 ,
Luiz G. Tone1
Copyright © 2009 by Ferrata Storti Foundation
Original Article |
A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups
1 Department of Pediatrics, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
2 Centro Infantil Boldrini, Campinas, Brazil
3 Pediatric Oncology Institute, Federal University of São Paulo, São Paulo, Brazil
4 Pediatric Clinic, University of Milano-Bicocca, Monza, Italy
5 Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil
Correspondence: Carlos Alberto Scrideli, Department of Pediatrics, Faculdade de Medicina de Ribeirão Preto, Avenida Bandeirantes 3900, Ribeirão Preto (SP), 14049-900, Brazil. E-mail:scrideli{at}fmrp.usp.br
Background: Minimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise.
Design and Methods: We analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements.
Results: At least one marker was detected by polymerase chain reaction in 96.4% of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis, those with positive B-derived CD10, patients positive for the TEL/AML1 transcript, and patients in morphological remission on a day 28 marrow, the event-free survival rate was found to be significantly lower in patients with positive minimal residual disease on day 28. Multivariate analysis demonstrated that the detection of minimal residual disease on day 28 is the most significant prognostic factor.
Conclusions: This simplified strategy for detection of minimal residual disease was feasible, reproducible, cheaper and simpler when compared with other methods, and allowed powerful discrimination between children with acute lymphoblastic leukemia with a good and poor outcome.
Key words: minimal residual disease, acute lymphoblastic leukemia, childhood, IG, TCR.
Related Article
Haematologica 2009 94: 748-752.
This article has been cited by other articles:
 |
|
 |
|
  M. Stanulla and A. Schrauder Bridging the gap between the north and south of the world: the case of treatment response in childhood acute lymphoblastic leukemia Haematologica, June 1, 2009; 94(6): 748 - 752. [Full Text] [PDF]
|
|