Kachur Ekaterina, Patel Jai N, Morse Allison L, Moore Donald C, Arnall Justin R
From Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.
J Adv Pract Oncol. 2023 Sep;14(6):520-532. doi: 10.6004/jadpro.2023.14.6.5. Epub 2023 Sep 1.
Cyclophosphamide remains a critical component to haploidentical transplant conditioning regimens. Post-transplant cyclophosphamide (PTCy) emerged as an effective component of graft-vs.-host disease (GVHD) prophylaxis in the nonmyeloablative haploidentical bone marrow transplant setting. The relative ease of administration compared with ex vivo manipulations and efficacy in reducing GVHD has led to increasing PTCy use in transplant centers around the world. The role of PTCy has expanded to haploidentical transplantation with myeloablative conditioning regimens and peripheral blood progenitor cells as the donor source. Moreover, encouraging results in GVHD management have been shown with the use of PTCy alone or in combination with other immunosuppressives in the human leukocyte antigen-matched donor setting. The toxicity profile of cyclophosphamide varies extensively depending on dose, duration, overall drug exposure, and, potentially, pharmacogenetics. This review highlights the pharmacology, pharmacokinetics, and toxic effects of cyclophosphamide and offers practical guidance for clinical application in the post-transplant setting. We summarize data on the management of high-dose cyclophosphamide toxicities and provide insights into the pharmacogenetic implications on drug efficacy and safety data.
环磷酰胺仍然是单倍体相合移植预处理方案的关键组成部分。移植后环磷酰胺（PTCy）在非清髓性单倍体相合骨髓移植中作为预防移植物抗宿主病（GVHD）的有效成分而出现。与体外操作相比，其给药相对简便，且在降低GVHD方面具有疗效，这导致全球移植中心对PTCy的使用不断增加。PTCy的作用已扩展到采用清髓性预处理方案且以外周血祖细胞作为供体来源的单倍体相合移植。此外，在人类白细胞抗原匹配供体的情况下，单独使用PTCy或与其他免疫抑制剂联合使用在GVHD管理方面已显示出令人鼓舞的结果。环磷酰胺的毒性特征因剂量、持续时间、总体药物暴露以及可能的药物遗传学而有很大差异。本综述重点介绍环磷酰胺的药理学、药代动力学和毒性作用，并为移植后临床应用提供实用指导。我们总结了高剂量环磷酰胺毒性管理的数据，并深入探讨药物遗传学对药物疗效和安全性数据的影响。
