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CANSEARCH RESEARCH LABORATORY
Pharmaco-oncogenetics group at platform of pediatric hemato-oncology (CANSEARCH Research Laboratory)
is interested in utilizing and inculcating pharmacogenetic knowledge in individualizing treatment options for
pediatric patients. The research by our team is aimed at improving the quality and effective patient care by
personalizing treatment options especially conditioning regimen, and immunosuppression prior to hematopoietic
stem cell transplantation (HSCT) based on the genetic makeup and phenotype of an individual. HSCT is a wellestablished therapeutic modality for chemotherapy resistant cases and advanced high risk group leukemic
patients. Major limitations for HSCT implication in children is conditioning regimen associated toxicity,
immunological complications such as graft versus host disease, infections associated with
immunocompromization, relapse of the disease or disease progression after the transplantation. Our group is
investigating options for individualizing intravenous chemotherapeutic (e.g busulfan (Bu)) treatment during the
conditioning of pediatric patients with Bu based regimens, since the regimen related toxicity and variability in
Bu pharmacokinetics is still one of the main obstacle influencing outcomes of HSCT in leukemic children. In
this regard, we are focused on therapeutic drug monitoring of patients to adjust Bu dose based on first dose
pharmacokinetic parameters, identifying, performing association studies of genetic markers in drug metabolizing
enzymes such as GSTA1, GSTM1, CYPs, and DNA repair genes in relation to the pharmacokinetics
/pharmacodynamics of Bu and the outcomes of HSCT in a multicentric prospective cohort of the European
Blood and Marrow Transplantation Group (EBMT) (ClinicalTrials.gov Identifier: NCT01257854) initiated by
our group. In addition to genotype or haplotype based analysis, our studies also emphasizes the importance of
other prognostic factors such as age, gender, co-medication and consideration of gene-environment interaction
models to predict the outcomes of treatment to large extent. Our group is also focused on investigating the role
of water soluble metabolites of Bu and cyclophosphamide in early events seen after HSCT, and related to
conditioning regimen. Further, functional studies on pharmacogenetic variants including genes coding for DNA
repair proteins, drug metabolizing enzymes are also interesting to us to establish the role of associations detected
in clinical studies. Our group works in collaboration with IBFM (International Berlin-Frankfurt-Munster)/EBMT
large multicentric study to validate and establish the utility of pharmacogenetic markers to personalize the
conditioning regimen prior to HSCT in leukemic children.
More details on group:
http://medweb1.unige.ch/recherche/groupes/b_donnees/sujet_907_4.html
https://cansearch.ch/
Dr Marc Ansari, MD , PD
Head of CANSEARCH research laboratory
Head of Clinical Onco-Hematology Unit
Pediatric department
Geneva University Hospital
Rue Willy-Donzé 6, 1211 Geneva 14
Switzerland
[email protected]
Selected Publications List
Patricia Huezo Diaz, Chakradhara Rao S Uppugunduri, Anuj Kumar Tyagi, Maja Krajinovic, Marc Ansari.
Pharmacogenetic aspects of drug metabolizing enzymes in busulfan based conditioning prior to allogenic
hematopoietic stem cell transplantation in children. Curr Drug Metab. 2014 Mar;15(3):251-64
Uppugunduri CR, MA Rezgui, Patricia Huego Diaz, Anuj Kumar Tyagi , Youssef Daali , M Duval, H
Bittencourt , M Krajinovic, M Ansari1. The association of cytochrome P450 genetic polymorphisms with
sulfolane formation and the efficacy of a busulfan-based conditioning regimen in pediatric patients undergoing
hematopoietic stem cell transplantation. Pharmacogenomics J. 2014 Jun;14(3):263-71
Ansari M, Théoret Y, Rezgui MA, Peters C, Mezziani S, Desjean C, Vachon MF, Champagne MA, Duval M,
Krajinovic M, Bittencourt H; Pediatric Disease Working Parties of the European Blood and Marrow Transplant
Group. Association between busulfan exposure and outcome in children receiving intravenous busulfan before
hematopoietic stem cell transplantation. Ther Drug Monit. 2014 Feb;36(1):93-9
Ansari M, Rezgui MA, Théoret Y, Uppugunduri CR, Mezziani S, Vachon MF, Desjean C, Rousseau J, Labuda
M, Przybyla C, Duval M, Champagne M, Peters C, Bittencourt H, Krajinovic M. Glutathione S transferase gene
variations influence busulfan pharmacokinetics and outcome of hematopoietic stem cell transplantation in
pediatric patients. Bone Marrow Transplant 2013; 48:939-46.
Marc Ansari, Uppugunduri CR, Sylvie Ferrari-Lacraz, Henrique Bittencourt, Fabienne Gumy-Pause, Yves
Chalandon, Jean-Marie Tiercy, Tal Schechter, Adam Gassas , John D. Doyle , Lee Dupuis, Michel Duval, Maja
Krajinovic, Jean Villard. The clinical relevance of pre-formed anti-HLA and anti- MICA antibodies after cord
blood transplantation in children. PLoS ONE 8(8): e72141. doi:10.1371/journal.pone.0072141.
Tyagi AK, Pradier A, Baumer O, Uppugunduri CR, Huezo-Diaz P, Posfay-Barbe KM, Roosnek E, Ansari M.
Validation of SYBR Green based quantification assay for the detection of human Torque Teno virus titers from
plasma. Virol J. 2013 Jun 11; 10:191. doi: 10.1186/1743-422X-10-191
François Versace, Uppugunduri CR, Yves Theoret, Hulya Ozsahin, Pierre Dayer, Jules Desmules, Marc Ansari.
A novel method for quantification of sulfolane (a metabolite of busulfan) in plasma by gas chromatographytandem mass spectrometry. Anal Bioanal Chem. 2012; 404:1831–1838
Ansari M, Uppugunduri CR, Déglon J, Théorêt Y, Versace F, Gumy-Pause F, Ozsahin H, Dayer P, Desmules J,
Daali Y. A simplified method for busulfan monitoring using dried blood spot in combination with liquid
chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2012;26:1437-46
Uppugunduri CR, Daali Y, Desmeules J, Dayer P, Krajinovic M, Ansari M. Transcriptional regulation of
CYP2C19 and its role in altered enzyme activity. Curr Drug Metab. 2012; 13:1196-1204.
Ansari M, Sauty G, Labuda M, Gagné V, Laverdière C, Moghrabi A, Sinnett D, Krajinovic M. Polymorphisms
in multidrug-resistance-associated protein gene 4 is associated with outcome in childhood aculte lymphoblastic
leukemia. Blood, vol. 114 (2009), No 7, pp. 1383-1386.