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

被引：5

作者：

Kasudhan, Kripa Shanker ^{[1
]}

Patil, Amol N. ^{[1
]}

Jandial, Aditya ^{[2
]}

Khadwal, Alka ^{[2
]}

Prakash, Gaurav ^{[2
]}

Jain, Arihant ^{[2
]}

Bhurani, Dinesh ^{[3
]}

Ahmed, Rayaz ^{[3
]}

Agrawal, Narendra ^{[3
]}

Singh, Reema ^{[3
]}

Sachdeva, Man Updesh Singh ^{[4
]}

Varma, Neelam ^{[4
]}

Das, Reena ^{[4
]}

Verma Attri, Savita ^{[5
]}

Malhotra, Samir ^{[1
]}

Majhail, Navneet S. ^{[6
]}

Malhotra, Pankaj ^{[2
]}

Lad, Deepesh P. ^{[2
]}

机构：

[1] Postgrad Inst Med Educ & Res, Dept Clin Pharmacol, Chandigarh, India

[2] Postgrad Inst Med Educ & Res, Dept Clin Hematol & Med Oncol, Chandigarh, India

[3] Rajiv Gandhi Canc Inst & Res Ctr, Dept Hematooncol, New Delhi, India

[4] Postgrad Inst Med Educ & Res, Dept Hematol, Chandigarh, India

[5] Postgrad Inst Med Educ & Res, Dept Pediat, Chandigarh, India

[6] Cleveland Clin, Dept Hematol Oncol, Blood & Marrow Transplant Program, Cleveland, OH USA

来源：

LEUKEMIA & LYMPHOMA | 2022年 / 63卷 / 11期

关键词：

PTCy; pharmacokinetics; CEPM; GVHD; haplo-HCT; VERSUS-HOST-DISEASE; DRUG-METABOLIZING-ENZYMES; POLYMORPHISMS; SURVIVAL; GVHD; TOXICITY; REGIMEN; RELAPSE; PLASMA;

D O I：

10.1080/10428194.2022.2087067

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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).

引用

页码：2679 / 2685

页数：7

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