1. Post-transplant cyclophosphamide pharmacokinetics and haploidentical hematopoietic cell transplantation outcomes: an exploratory study.
- Author
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Kasudhan, Kripa Shanker, Patil, Amol N., Jandial, Aditya, Khadwal, Alka, Prakash, Gaurav, Jain, Arihant, Bhurani, Dinesh, Ahmed, Rayaz, Agrawal, Narendra, Singh, Reema, Sachdeva, Man Updesh Singh, Varma, Neelam, Das, Reena, Verma Attri, Savita, Malhotra, Samir, Majhail, Navneet S., Malhotra, Pankaj, and Lad, Deepesh P.
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HEMATOPOIETIC stem cell transplantation , *TREATMENT effectiveness , *PHARMACOKINETICS , *CYCLOPHOSPHAMIDE , *GRAFT versus host disease - Abstract
Pharmacokinetics of cyclophosphamide has been explored to optimize conditioning dosing. We hypothesized that post-transplant cyclophosphamide (PTCy) metabolite carboxy-ethyl phosphoramide mustard (CEPM) pharmacokinetics might impact haploidentical transplantation (haplo-HCT) outcomes. CEPM area under the curve (AUC0–48) was determined by eleven sampling timepoints on day +3/+4 using LC-MS/MS. The median CEPM AUC0–48 in a cohort of 30 patients was 14.2 (14) mg·hr/L. The incidence of severe chronic graft-versus-host disease (GVHD) (73% vs. 11%, p = 0.02), and GVHD-/relapse-free survival (GRFS) was significantly inferior in the CEPM AUC0–48 < 14 mg·hr/L group (54 days vs. 344 days, p = 0.02). There was, however, no difference in grade III-IV acute GVHD (38% vs. 14%, p = 0.12) and overall survival (295 days vs. not reached, p = 0.2). CEPM AUC0–48, is associated with severe chronic GVHD and GRFS post-haplo-HCT in this exploratory study. There is scope for personalizing day + 4 PTCy dose based on day + 3 CEPM AUC0–8. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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