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

Autor: Kasudhan KS; Department of Clinical Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Patil AN; Department of Clinical Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Jandial A; Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Khadwal A; Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Prakash G; Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Jain A; Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Bhurani D; Department of Hemato-Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India., Ahmed R; Department of Hemato-Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India., Agrawal N; Department of Hemato-Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India., Singh R; Department of Hemato-Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India., Sachdeva MUS; Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Varma N; Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Das R; Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Verma Attri S; Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Malhotra S; Department of Clinical Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Majhail NS; Blood and Marrow Transplant Program, Department of Hematology-Oncology, Cleveland Clinic, Cleveland, OH, USA., Malhotra P; Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Lad DP; Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Jazyk: angličtina
Zdroj: Leukemia & lymphoma [Leuk Lymphoma] 2022 Nov; Vol. 63 (11), pp. 2679-2685. Date of Electronic Publication: 2022 Jun 14.
DOI: 10.1080/10428194.2022.2087067
Abstrakt: 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·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·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 .
Databáze: MEDLINE
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