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

被引:11
作者
Admiraal, R. [1 ,2 ]
Boelens, J. J. [1 ,2 ]
机构
[1] Univ Med Ctr Utrecht, Pediatr Blood & Marrow Transplant Program, POB 85090, NL-3508 AB Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Lab Translat Immunol, U DANCE, NL-3508 AB Utrecht, Netherlands
关键词
Cord blood; individualized dosing; hematopoietic cell transplantation; PK/PD; STEM-CELL TRANSPLANTATION; BUSULFAN PLUS CYCLOPHOSPHAMIDE; ACUTE MYELOID-LEUKEMIA; IMMUNE RECONSTITUTION; BONE-MARROW; T-CELLS; INTRAVENOUS BUSULFAN; PREPARATIVE REGIMEN; PEDIATRIC-PATIENTS; POPULATION PHARMACOKINETICS;
D O I
10.1517/14712598.2016.1164688
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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. Antithymocyte 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.
引用
收藏
页码:801 / 813
页数:13
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