Assessment of circulating biomarkers for potential pharmacodynamic utility in patients with lymphoma

A. Greystoke; J. P B O'Connor; K. Linton; M. B. Taylor; J. Cummings; T. Ward; F. Maders; A. Hughes; M. Ranson; T. M. Illidge; J. Radford; C. Dive

doi:10.1038/sj.bjc.6606082

Assessment of circulating biomarkers for potential pharmacodynamic utility in patients with lymphoma

A. Greystoke, J. P B O'Connor, K. Linton, M. B. Taylor, J. Cummings, T. Ward, F. Maders, A. Hughes, M. Ranson, T. M. Illidge, J. Radford, C. Dive

Cancer Research UK Manchester Institute

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose:Treatment efficacy and toxicity are difficult to predict in lymphoma patients. In this study, the utility of circulating biomarkers in predicting and/or monitoring treatment efficacy/toxicity were investigated.Patients and methodsCirculating biomarkers of cell death (nucleosomal DNA (nDNA) and cytokeratin 18 (CK18)), and circulating FLT3 ligand, a potential biomarker of myelosuppression, were assessed before and serially after standard chemotherapy in 49 patients with Hodgkin and non-Hodgkin lymphoma. Cytokeratin 18 is not expressed in lymphoma cells so is a potential biomarker of epithelial toxicity in this setting. Tumour response was assessed before and after completion of chemotherapy by 2D and 3D computed tomography radiological response.Results:Baseline nDNA level was significantly higher in all lymphoma subtypes compared with 61 healthy controls and was prognostic for progression-free survival in diffuse large B-cell lymphoma (DLBCL). Decreases in nDNA levels were observed in the first week after chemotherapy; in FL, early falls in nDNA predicted for long remission following therapy. In DLBCL, elevations in nDNA occurred in cases with progressive disease. Circulating CK18 increased within 48 h of chemotherapy and was significantly higher in patients experiencing epithelial toxicity graded 3 by Common Terminology for Classification of Adverse Events criteria. FLT3 ligand was elevated within 3-8 days of chemotherapy initiation and predicted those patients who subsequently developed neutropenic sepsis.Conclusion:These data suggest circulating biomarkers contribute useful information regarding tumour response and toxicity in patients receiving standard chemotherapy and have potential utility in the development of individualised treatment approaches in lymphoma. These biomarkers are now being tested within multicentre phase III trials to progress their qualification. © 2011 Cancer Research UK. All rights reserved.

Original language	English
Pages (from-to)	719-725
Number of pages	6
Journal	British Journal of Cancer
Volume	104
Issue number	4
DOIs	https://doi.org/10.1038/sj.bjc.6606082
Publication status	Published - 15 Feb 2011

Keywords

biomarkers
cytokeratin 18
FLT3 ligand
Hodgkin and non-Hodgkin lymphoma
nucleosomal DNA

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.bjc.6606082

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title = "Assessment of circulating biomarkers for potential pharmacodynamic utility in patients with lymphoma",

abstract = "Purpose:Treatment efficacy and toxicity are difficult to predict in lymphoma patients. In this study, the utility of circulating biomarkers in predicting and/or monitoring treatment efficacy/toxicity were investigated.Patients and methodsCirculating biomarkers of cell death (nucleosomal DNA (nDNA) and cytokeratin 18 (CK18)), and circulating FLT3 ligand, a potential biomarker of myelosuppression, were assessed before and serially after standard chemotherapy in 49 patients with Hodgkin and non-Hodgkin lymphoma. Cytokeratin 18 is not expressed in lymphoma cells so is a potential biomarker of epithelial toxicity in this setting. Tumour response was assessed before and after completion of chemotherapy by 2D and 3D computed tomography radiological response.Results:Baseline nDNA level was significantly higher in all lymphoma subtypes compared with 61 healthy controls and was prognostic for progression-free survival in diffuse large B-cell lymphoma (DLBCL). Decreases in nDNA levels were observed in the first week after chemotherapy; in FL, early falls in nDNA predicted for long remission following therapy. In DLBCL, elevations in nDNA occurred in cases with progressive disease. Circulating CK18 increased within 48 h of chemotherapy and was significantly higher in patients experiencing epithelial toxicity graded 3 by Common Terminology for Classification of Adverse Events criteria. FLT3 ligand was elevated within 3-8 days of chemotherapy initiation and predicted those patients who subsequently developed neutropenic sepsis.Conclusion:These data suggest circulating biomarkers contribute useful information regarding tumour response and toxicity in patients receiving standard chemotherapy and have potential utility in the development of individualised treatment approaches in lymphoma. These biomarkers are now being tested within multicentre phase III trials to progress their qualification. {\textcopyright} 2011 Cancer Research UK. All rights reserved.",

keywords = "biomarkers, cytokeratin 18, FLT3 ligand, Hodgkin and non-Hodgkin lymphoma, nucleosomal DNA",

author = "A. Greystoke and O'Connor, {J. P B} and K. Linton and Taylor, {M. B.} and J. Cummings and T. Ward and F. Maders and A. Hughes and M. Ranson and Illidge, {T. M.} and J. Radford and C. Dive",

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doi = "10.1038/sj.bjc.6606082",

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T1 - Assessment of circulating biomarkers for potential pharmacodynamic utility in patients with lymphoma

AU - Greystoke, A.

AU - O'Connor, J. P B

AU - Linton, K.

AU - Taylor, M. B.

AU - Cummings, J.

AU - Ward, T.

AU - Maders, F.

AU - Hughes, A.

AU - Ranson, M.

AU - Illidge, T. M.

AU - Radford, J.

AU - Dive, C.

PY - 2011/2/15

Y1 - 2011/2/15

N2 - Purpose:Treatment efficacy and toxicity are difficult to predict in lymphoma patients. In this study, the utility of circulating biomarkers in predicting and/or monitoring treatment efficacy/toxicity were investigated.Patients and methodsCirculating biomarkers of cell death (nucleosomal DNA (nDNA) and cytokeratin 18 (CK18)), and circulating FLT3 ligand, a potential biomarker of myelosuppression, were assessed before and serially after standard chemotherapy in 49 patients with Hodgkin and non-Hodgkin lymphoma. Cytokeratin 18 is not expressed in lymphoma cells so is a potential biomarker of epithelial toxicity in this setting. Tumour response was assessed before and after completion of chemotherapy by 2D and 3D computed tomography radiological response.Results:Baseline nDNA level was significantly higher in all lymphoma subtypes compared with 61 healthy controls and was prognostic for progression-free survival in diffuse large B-cell lymphoma (DLBCL). Decreases in nDNA levels were observed in the first week after chemotherapy; in FL, early falls in nDNA predicted for long remission following therapy. In DLBCL, elevations in nDNA occurred in cases with progressive disease. Circulating CK18 increased within 48 h of chemotherapy and was significantly higher in patients experiencing epithelial toxicity graded 3 by Common Terminology for Classification of Adverse Events criteria. FLT3 ligand was elevated within 3-8 days of chemotherapy initiation and predicted those patients who subsequently developed neutropenic sepsis.Conclusion:These data suggest circulating biomarkers contribute useful information regarding tumour response and toxicity in patients receiving standard chemotherapy and have potential utility in the development of individualised treatment approaches in lymphoma. These biomarkers are now being tested within multicentre phase III trials to progress their qualification. © 2011 Cancer Research UK. All rights reserved.

AB - Purpose:Treatment efficacy and toxicity are difficult to predict in lymphoma patients. In this study, the utility of circulating biomarkers in predicting and/or monitoring treatment efficacy/toxicity were investigated.Patients and methodsCirculating biomarkers of cell death (nucleosomal DNA (nDNA) and cytokeratin 18 (CK18)), and circulating FLT3 ligand, a potential biomarker of myelosuppression, were assessed before and serially after standard chemotherapy in 49 patients with Hodgkin and non-Hodgkin lymphoma. Cytokeratin 18 is not expressed in lymphoma cells so is a potential biomarker of epithelial toxicity in this setting. Tumour response was assessed before and after completion of chemotherapy by 2D and 3D computed tomography radiological response.Results:Baseline nDNA level was significantly higher in all lymphoma subtypes compared with 61 healthy controls and was prognostic for progression-free survival in diffuse large B-cell lymphoma (DLBCL). Decreases in nDNA levels were observed in the first week after chemotherapy; in FL, early falls in nDNA predicted for long remission following therapy. In DLBCL, elevations in nDNA occurred in cases with progressive disease. Circulating CK18 increased within 48 h of chemotherapy and was significantly higher in patients experiencing epithelial toxicity graded 3 by Common Terminology for Classification of Adverse Events criteria. FLT3 ligand was elevated within 3-8 days of chemotherapy initiation and predicted those patients who subsequently developed neutropenic sepsis.Conclusion:These data suggest circulating biomarkers contribute useful information regarding tumour response and toxicity in patients receiving standard chemotherapy and have potential utility in the development of individualised treatment approaches in lymphoma. These biomarkers are now being tested within multicentre phase III trials to progress their qualification. © 2011 Cancer Research UK. All rights reserved.

KW - biomarkers

KW - cytokeratin 18

KW - FLT3 ligand

KW - Hodgkin and non-Hodgkin lymphoma

KW - nucleosomal DNA

U2 - 10.1038/sj.bjc.6606082

DO - 10.1038/sj.bjc.6606082

M3 - Article

C2 - 21245866

SN - 0007-0920

VL - 104

SP - 719

EP - 725

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 4

ER -

Assessment of circulating biomarkers for potential pharmacodynamic utility in patients with lymphoma

Abstract

Keywords

UN SDGs

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