Minimal residual disease-guided treatment deintensilication for children with Acute Lyrnphoblastic Leukemia: results from the Malaysia-Singapore Acuten Lymphobiastic Leukemia 2003 Study

Yeoh, A.E.J. and Ariffin, H. and Chai, E.L.L. and Kwok, C.S.N. and Chan, Y.H. and Ponnudurai, K. and Campana, D. and Tan, P.L. and Chan, M.Y. and Kham, S.K.Y. and Chong, L.A. and Tan, A.M. and Lin, H.P. and Quah, T.C. (2012) Minimal residual disease-guided treatment deintensilication for children with Acute Lyrnphoblastic Leukemia: results from the Malaysia-Singapore Acuten Lymphobiastic Leukemia 2003 Study. Journal of Clinical Oncology, 30 (19). ISSN 0732-183X,

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Abstract

Purpose To improve treatment outcome for childhood acute lymphoblactic leukemia (ALL, we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement. Patients and Methods Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Munster-All treatment. High-risk ALL was defined by MRD ≥ 1 x 10¯³ at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 x 10¯4 at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients. Results Patents who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n=172;31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n=101;18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n=283;51%) Conclusion Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for chilhood ALL.

Item Type:	Article
Funders:	UNSPECIFIED
Uncontrolled Keywords:	Residual Disease-Guided Treatment; Deintensilication; Acute Lyrnphoblastic Leukemia; Malaysia-Singapore Acute Lymphobiastic Leukemia 2003 Study
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medicine
Depositing User:	Ms. Jamilah Salleh
Date Deposited:	14 Oct 2014 01:48
Last Modified:	14 Oct 2014 01:48
URI:	http://eprints.um.edu.my/id/eprint/10506

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