Personalized Chimerism Test that Uses Selection of Short Tandem Repeat or Quantitative PCR Depending on Patient's Chimerism Status

Jennifer Tyler, Lorie Kumer, Carolyn Fisher, Heather Casey, Hiroko Shike

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Chimerism testing is used to monitor engraftment and risk of relapse after allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Although short tandem repeat (STR) method is widely used among clinical laboratories, quantitative PCR (qPCR) provides better sensitivity (0.1%) than STR (1% to 5%) but is less accurate than STR for patients in mixed chimerism. qPCR chimerism allows evaluation of residual recipient cells as a surrogate of measurable residual disease. To achieve higher sensitivity and accuracy, we applied qPCR or STR based on patient chimerism status (recipient alleles <5% or ≥5%, respectively). Of the 230 patients tested by STR in a 1-year period, excluding 10 deceased patients, 30 qPCR markers were genotyped and 167 patients converted to qPCR chimerism (76%), including eight patients undergoing multiple-donor transplantation. STR was continued on 53 patients (24%) for the following reasons: mixed chimerism (n = 23), lack of donor or pretransplantation DNA (n = 22), and insufficient qPCR informative markers [8 of 60 patients with related donors (13.3%)]. qPCR detected residual recipient chimerism in 85.5% of patients with complete chimerism by STR (<5% recipient). Selecting STR or qPCR testing based on each patient's chimerism status facilitates sensitive and accurate chimerism testing in clinical settings. In addition, we discuss clinical relevance of chimerism testing for measurable residual disease detection in various hematologic malignancies.

Original languageEnglish (US)
Pages (from-to)483-490
Number of pages8
JournalJournal of Molecular Diagnostics
Volume21
Issue number3
DOIs
StatePublished - May 2019

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Chimerism
Microsatellite Repeats
Polymerase Chain Reaction
Tissue Donors
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Transplantation
Alleles

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Medicine

Cite this

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title = "Personalized Chimerism Test that Uses Selection of Short Tandem Repeat or Quantitative PCR Depending on Patient's Chimerism Status",
abstract = "Chimerism testing is used to monitor engraftment and risk of relapse after allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Although short tandem repeat (STR) method is widely used among clinical laboratories, quantitative PCR (qPCR) provides better sensitivity (0.1{\%}) than STR (1{\%} to 5{\%}) but is less accurate than STR for patients in mixed chimerism. qPCR chimerism allows evaluation of residual recipient cells as a surrogate of measurable residual disease. To achieve higher sensitivity and accuracy, we applied qPCR or STR based on patient chimerism status (recipient alleles <5{\%} or ≥5{\%}, respectively). Of the 230 patients tested by STR in a 1-year period, excluding 10 deceased patients, 30 qPCR markers were genotyped and 167 patients converted to qPCR chimerism (76{\%}), including eight patients undergoing multiple-donor transplantation. STR was continued on 53 patients (24{\%}) for the following reasons: mixed chimerism (n = 23), lack of donor or pretransplantation DNA (n = 22), and insufficient qPCR informative markers [8 of 60 patients with related donors (13.3{\%})]. qPCR detected residual recipient chimerism in 85.5{\%} of patients with complete chimerism by STR (<5{\%} recipient). Selecting STR or qPCR testing based on each patient's chimerism status facilitates sensitive and accurate chimerism testing in clinical settings. In addition, we discuss clinical relevance of chimerism testing for measurable residual disease detection in various hematologic malignancies.",
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Personalized Chimerism Test that Uses Selection of Short Tandem Repeat or Quantitative PCR Depending on Patient's Chimerism Status. / Tyler, Jennifer; Kumer, Lorie; Fisher, Carolyn; Casey, Heather; Shike, Hiroko.

In: Journal of Molecular Diagnostics, Vol. 21, No. 3, 05.2019, p. 483-490.

Research output: Contribution to journalArticle

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