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.
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Acknowledgments
We want to acknowledge the contributions of Ms. Jyotsna Kapoor to this work. As we mourn her loss to COVID-19, we would like to thank all frontline workers for putting their work above themselves to serve humanity.
Authors’ contributions
DPL and ANP conceived the study. KSK, ANP, DPL, NV analyzed the lab data. DPL, ANP, and KSK drafted the manuscript. All authors were involved in patient recruitment, clinical care of the patients, and manuscript writing. DPL, ANP, and KSK confirm full access to the data in the study and final responsibility for the manuscript.
Disclosure statement
All other authors have no conflicts of interest to disclose.