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

共 27 条

[1] A pilot pharmacologic biomarker study in HLA-haploidentical hematopoietic cell transplant recipients [J].

Bemer, Meagan J. ;

Sorror, Mohamed ;

Sandmaier, Brenda M. ;

O'Donnell, Paul V. ;

McCune, Jeannine S. .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2013, 72 (03) :607-618

[2] Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin [J].

Ekhart, Corine ;

Rodenhuis, Sjoerd ;

Smits, Paul H. M. ;

Beijnen, Jos H. ;

Hultema, Alwin D. R. .

PHARMACOGENETICS AND GENOMICS, 2008, 18 (11) :1009-1015

[3] Influence of polymorphisms of drug metabolizing enzymes (CYP2136, CYP2C9, CYPX19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide [J].

Ekhart, Corine ;

Doodeman, Valerie D. ;

Rodenhuis, Sjoerd ;

Smits, Paul H. M. ;

Beijnen, Jos H. ;

Huitema, Alwin D. R. .

PHARMACOGENETICS AND GENOMICS, 2008, 18 (06) :515-523

[4] Simultaneous quantification of cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) [J].

Ekhart, Corine ;

Gebretensae, Abadi ;

Rosing, Hilde ;

Rodenhuis, Sjoerd ;

Beijnen, Jos H. ;

Huitema, Alwin D. R. .

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2007, 854 (1-2) :345-349

[5] International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium [J].

Harris, Andrew C. ;

Young, Rachel ;

Devine, Steven ;

Hogan, William J. ;

Ayuk, Francis ;

Bunworasate, Udomsak ;

Chanswangphuwana, Chantiya ;

Efebera, Yvonne A. ;

Holler, Ernst ;

Litzow, Mark ;

Ordemann, Rainer ;

Qayed, Muna ;

Renteria, Anne S. ;

Reshef, Ran ;

Woelfl, Matthias ;

Chen, Yi-Bin ;

Goldstein, Steven ;

Jagasia, Madan ;

Locatelli, Franco ;

Mielke, Stephan ;

Porter, David ;

Schechter, Tal ;

Shekhovtsova, Zhanna ;

Ferrara, James L. M. ;

Levine, John E. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2016, 22 (01) :4-10

[6]

Hassan M, 2013, PHARMACOGENOMICS, V14, P75, DOI [10.2217/PGS.12.185, 10.2217/pgs.12.185]

[7] Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide [J].

Im, Annie ;

Rashidi, Armin ;

Wang, Tao ;

Hemmer, Michael ;

MacMillan, Margaret L. ;

Pidala, Joseph ;

Jagasia, Madan ;

Pavletic, Steven ;

Majhail, Navneet S. ;

Weisdorf, Daniel ;

Abdel-Azim, Hisham ;

Agrawal, Vaibhav ;

Al-Homsi, A. Samer ;

Aljurf, Mahmoud ;

Askar, Medhat ;

Auletta, Jeffery J. ;

Bashey, Asad ;

Beitinjaneh, Amer ;

Bhatt, Vijaya Raj ;

Byrne, Michael ;

Cahn, Jean-Yves ;

Cairo, Mitchell ;

Castillo, Paul ;

Cerny, Jan ;

Chhabra, Saurabh ;

Choe, Hannah ;

Ciurea, Stefan ;

Daly, Andrew ;

Diaz Perez, Miguel Angel ;

Farhadfar, Nosha ;

Gadalla, Shahinaz M. ;

Gale, Robert ;

Ganguly, Siddhartha ;

Gergis, Usama ;

Hanna, Rabi ;

Hematti, Peiman ;

Herzig, Roger ;

Hildebrandt, Gerhard C. ;

Lad, Deepesh P. ;

Lee, Catherine ;

Lehmann, Leslie ;

Lekakis, Lazaros ;

Kamble, Rammurti T. ;

Kharfan-Dabaja, Mohamed A. ;

Khandelwal, Pooja ;

Martino, Rodrigo ;

Murthy, Hemant S. ;

Nishihori, Taiga ;

O'Brien, Tracey A. ;

Olsson, Richard F. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2020, 26 (08) :1459-1468

[8] National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report [J].

Jagasia, Madan H. ;

Greinix, Hildegard T. ;

Arora, Mukta ;

Williams, Kirsten M. ;

Wolff, Daniel ;

Cowen, Edward W. ;

Palmer, Jeanne ;

Weisdorf, Daniel ;

Treister, Nathaniel S. ;

Cheng, Guang-Shing ;

Kerr, Holly ;

Stratton, Pamela ;

Duarte, Rafael F. ;

McDonald, George B. ;

Inamoto, Yoshihiro ;

Vigorito, Afonso ;

Arai, Sally ;

Datiles, Manuel B. ;

Jacobsohn, David ;

Heller, Theo ;

Kitko, Carrie L. ;

Mitchell, Sandra A. ;

Martin, Paul J. ;

Shulman, Howard ;

Wu, Roy S. ;

Cutler, Corey S. ;

Vogelsang, Georgia B. ;

Lee, Stephanie J. ;

Pavletic, Steven Z. ;

Flowers, Mary E. D. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2015, 21 (03) :389-401

[9] Rapid quantitation of cyclophosphamide metabolites in plasma by liquid chromatography-mass spectrometry [J].

Kalhorn, TF ;

Howald, WN ;

Cole, S ;

Phillips, B ;

Wang, J ;

Slattery, JT ;

McCune, JS .

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2006, 835 (1-2) :105-113

[10]

Kanakry CG, 2016, NAT REV CLIN ONCOL, V13, P10, DOI [10.1038/nrclinonc.2015.128, 10.1038/nrclinonc.2015.234]

← 1 2 3 →