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

R Admiraal, J J Boelens

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)801-813
Number of pages13
JournalExpert Opinion on Biological Therapy
Volume16
Issue number6
DOIs
Publication statusPublished - Jun 2016

Keywords

  • cord blood
  • individualized dosing
  • hematopoietic cell transplantation
  • PK/PD

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