4.3 Article

Post-transplant cyclophosphamide pharmacokinetics and haploidentical hematopoietic cell transplantation outcomes: an exploratory study

Journal

LEUKEMIA & LYMPHOMA
Volume 63, Issue 11, Pages 2679-2685

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2022.2087067

Keywords

PTCy; pharmacokinetics; CEPM; GVHD; haplo-HCT

Funding

  1. Indian Council of Medical Research [ICMR IRIS] [2020-2997]

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This study investigated the pharmacokinetics of cyclophosphamide in haploidentical transplantation and found an association between CEPM AUC(0-48) and severe chronic GVHD and GRFS.
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 (AUC(0-48)) was determined by eleven sampling timepoints on day +3/+4 using LC-MS/MS. The median CEPM AUC(0-48) in a cohort of 30 patients was 14.2 (14) mg center dot 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 AUC(0-48) < 14 mg center dot 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 AUC(0-48,) 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 AUC(0-8).

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