%0 Journal Article
%T Post-transplant cyclophosphamide pharmacokinetics and haploidentical hematopoietic cell transplantation outcomes: an exploratory study.
%A Kasudhan KS
%A Patil AN
%A Jandial A
%A Khadwal A
%A Prakash G
%A Jain A
%A Bhurani D
%A Ahmed R
%A Agrawal N
%A Singh R
%A Sachdeva MUS
%A Varma N
%A Das R
%A Verma Attri S
%A Malhotra S
%A Majhail NS
%A Malhotra P
%A Lad DP
%J Leuk Lymphoma
%V 63
%N 11
%D Nov 2022
%M 35699967
暂无%R 10.1080/10428194.2022.2087067
%X 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.