title: Individualized conditioning regimes in cord blood transplantation: Towards improved and predictable safety and efficacy.
abstract: The conditioning regimen used in cord blood transplantation (CBT) may significantly impact the outcomes. Variable pharmacokinetics (PK) of drugs used may further influence outcome. Individualized dosing takes inter-patient differences in PK into account, tailoring drug dose for each individual patient in order to reach optimal exposure. Dose individualization may result in a better predictable regimen in terms of safety and efficacy, including timely T cell reconstitution, which may result in improved survival chances.
  
  
  
  Conditioning regimens used in CBT varies significantly between and within centres. For busulfan, individualized dosing with therapeutic drug monitoring has resulted in better outcomes. Anti-thymocyte globulin (ATG), used to prevent rejection and GvHD, significantly hampers early T-cell reconstitution (IR). Timely IR is crucial in preventing viral reactivations and relapse. By individudalizing ATG, IR is better predicted and may prevent morbidity and mortality.
  
  
  
  Individualization of agents used in the conditioning regimen in CBT has proven its added value. Further fine-tuning, including new drugs and/or comprehensive models for all drugs, may result in better predictable conditioning regimens. A predictable conditioning regimen is also of interest/importance when studying adjuvant therapies, including immunotherapies (e.g. cellular vaccines or engineered T-cell) in a harmonized clinical trial design setting.
authors.affiliation: a Pediatric Blood and Marrow Transplant Program , University Medical Center Utrecht , Utrecht , The Netherlands.|b U-DANCE, Laboratory of Translational Immunology , University Medical Centre Utrecht , Utrecht , The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Admiraal
authors.affiliation: a Pediatric Blood and Marrow Transplant Program , University Medical Center Utrecht , Utrecht , The Netherlands.|b U-DANCE, Laboratory of Translational Immunology , University Medical Centre Utrecht , Utrecht , The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Boelens
mesh_terms: D000818:Animals; D005312:Fetal Blood / Q000276:immunology / Q000378:metabolism / Q000502:physiology / Q000637:transplantation*; D005544:Forecasting; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D057285:Precision Medicine / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome
keywords: Cord blood; PK/PD; hematopoietic cell transplantation; individualized dosing