Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group

Blood
Stella M DaviesMary V Relling

Abstract

Minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of induction therapy in more than 1000 children enrolled in Pediatric Oncology Group therapy protocols 9904, 9905, and 9906. We classified patients as "best risk" if they had cleared MRD by day 8 of therapy and as "worst risk" if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related to polymorphisms in 16 loci in genes hypothesized to influence response to therapy in acute lymphoblastic leukemia (ALL). After adjusting for known prognostic features such as presence of the TEL-AML1 rearrangement, National Cancer Institute (NCI) risk status, ploidy, and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with more favorable MRD status than the A allele (P = .009, logistic regression), when comparing "best" and "worst" risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer th...Continue Reading

References

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Citations

Jan 30, 2009·JAMA : the Journal of the American Medical Association·Jun J YangMary V Relling
Feb 27, 2009·Current Opinion in Pediatrics·Lynda M Vrooman, Lewis B Silverman
Nov 8, 2008·Journal of Pediatric Hematology/oncology·Marie Louise DavidsenKjeld Schmiegelow
Jul 23, 2013·Blood Reviews·Anna MartnerKristoffer Hellstrand
Aug 11, 2010·Journal of Clinical Gastroenterology·Sara De IudicibusGiuliana Decorti
Mar 29, 2014·Expert Opinion on Drug Metabolism & Toxicology·Stéphanie DulucqMaja Krajinovic
Jun 16, 2012·Immunology Letters·J Guergnon, C Combadière
Sep 26, 2009·Clinical Lymphoma & Myeloma·Deepa BhojwaniChing-Hon Pui
Dec 23, 2008·Seminars in Hematology·Meyling H CheokWilliam E Evans
May 14, 2014·Advances in Hematology·Carlos Eduardo Coral de OliveiraMaria Angelica Ehara Watanabe
May 3, 2005·Leukemia Research·M TsurusawaUNKNOWN MDS committee of the Japanese Society of Pediatric Hematology
May 1, 2010·Expert Opinion on Pharmacotherapy·Nathan D MeekerJoshua D Schiffman
Sep 23, 2016·Minerva pediatrica·Qi AnMingwei Jin
Sep 26, 2017·Analytical Chemistry·Caroline E Hansen, Wilbur A Lam

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