{"title":"Post-transplant cyclophosphamide pharmacokinetics and haploidentical hematopoietic cell transplantation outcomes: an exploratory study.","authors":"Kripa Shanker Kasudhan, Amol N Patil, Aditya Jandial, Alka Khadwal, Gaurav Prakash, Arihant Jain, Dinesh Bhurani, Rayaz Ahmed, Narendra Agrawal, Reema Singh, Man Updesh Singh Sachdeva, Neelam Varma, Reena Das, Savita Verma Attri, Samir Malhotra, Navneet S Majhail, Pankaj Malhotra, Deepesh P Lad","doi":"10.1080/10428194.2022.2087067","DOIUrl":null,"url":null,"abstract":"<p><p>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<sub>0-48</sub>) was determined by eleven sampling timepoints on day +3/+4 using LC-MS/MS. The median CEPM AUC<sub>0-48</sub> 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%, <i>p</i> = 0.02), and GVHD-/relapse-free survival (GRFS) was significantly inferior in the CEPM AUC<sub>0-48</sub> < 14 mg·hr/L group (54 days vs. 344 days, <i>p</i> = 0.02). There was, however, no difference in grade III-IV acute GVHD (38% vs. 14%, <i>p</i> = 0.12) and overall survival (295 days vs. not reached, <i>p</i> = 0.2). CEPM AUC<sub>0-48,</sub> 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<sub>0-8</sub>.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":"63 11","pages":"2679-2685"},"PeriodicalIF":2.2000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia & Lymphoma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10428194.2022.2087067","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 2
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.
期刊介绍：
Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor
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