Individualized conditioning regimes in cord blood transplantation: Towards improved and predictable safety and efficacy

Expert Opin Biol Ther. 2016 Jun;16(6):801-13. doi: 10.1517/14712598.2016.1164688. Epub 2016 Mar 28.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: Cord blood; PK/PD; hematopoietic cell transplantation; individualized dosing.

MeSH terms

  • Animals
  • Fetal Blood / immunology
  • Fetal Blood / metabolism
  • Fetal Blood / physiology
  • Fetal Blood / transplantation*
  • Forecasting
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / metabolism
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Precision Medicine / methods*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous / methods
  • Treatment Outcome