Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing

Kurtz, David M., Green, Michael R., Bratman, Scott V., Scherer, Florian, Liu, Chih Long, Kunder, Christian A., Takahashi, Kazuhiro, Glover, Cynthia, Keane, Colm, Kihira, Shingo, Visser, Brendan, Callahan, Jason, Kong, Katherine A., Faham, Malek, Corbelli, Karen S., Miklos, David, Advani, Ranjana H., Levy, Ronald, Hicks, Rodney J., Hertzberg, Mark, Ohgami, Robert S., Gandhi, Maher K., Diehn, Maximilian and Alizadeh, Ash A. (2015) Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing. Blood, 125 24: 3679-3687. doi:10.1182/blood-2015-03-635169

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Author Kurtz, David M.
Green, Michael R.
Bratman, Scott V.
Scherer, Florian
Liu, Chih Long
Kunder, Christian A.
Takahashi, Kazuhiro
Glover, Cynthia
Keane, Colm
Kihira, Shingo
Visser, Brendan
Callahan, Jason
Kong, Katherine A.
Faham, Malek
Corbelli, Karen S.
Miklos, David
Advani, Ranjana H.
Levy, Ronald
Hicks, Rodney J.
Hertzberg, Mark
Ohgami, Robert S.
Gandhi, Maher K.
Diehn, Maximilian
Alizadeh, Ash A.
Title Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing
Journal name Blood   Check publisher's open access policy
ISSN 1528-0020
Publication date 2015-06-11
Year available 2015
Sub-type Article (original research)
DOI 10.1182/blood-2015-03-635169
Open Access Status DOI
Volume 125
Issue 24
Start page 3679
End page 3687
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Language eng
Formatted abstract
Recent studies have shown limited utility of routine surveillance imaging for diffuse large B-cell lymphoma (DLBCL) patients achieving remission. Detection of molecular disease by immunoglobulin high-throughput sequencing (Ig-HTS) from peripheral blood provides an alternate strategy for surveillance. We prospectively evaluated the utility of Ig-HTS within 311 blood and 105 tumor samples from 75 patients with DLBCL, comparing Ig-HTS from the cellular (circulating leukocytes) and acellular (plasma cell-free DNA) compartments of peripheral blood to clinical outcomes and 18fluoro-deoxyglucose positron emission tomography combined with computed tomography (PET/CT; n = 173). Clonotypic immunoglobulin rearrangements were detected in 83% of patients with adequate tumor samples to enable subsequent monitoring in peripheral blood. Molecular disease measured from plasma, compared with circulating leukocytes, was more abundant and better correlated with radiographic disease burden. Before treatment, molecular disease was detected in the plasma of 82% of patients compared with 71% in circulating cells (P = .68). However, molecular disease was detected significantly more frequently in the plasma at time of relapse (100% vs 30%; P = .001). Detection of molecular disease in the plasma often preceded PET/CT detection of relapse in patients initially achieving remission. During surveillance time points before relapse, plasma Ig-HTS demonstrated improved specificity (100% vs 56%, P < .0001) and similar sensitivity (31% vs 55%, P = .4) compared with PET/CT. Given its high specificity, Ig-HTS from plasma has potential clinical utility for surveillance after complete remission.
Keyword Hematology
Cancer detection
Blood -- Analysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 45 times in Thomson Reuters Web of Science Article | Citations
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