A QA program for MRD testing demonstrates that systematic education can reduce discordance among experienced interpreters

Michael Keeney, Brent L. Wood, Benjamin D. Hedley, Joseph A. Digiuseppe, Maryalice Stetler-Stevenson, Elisabeth M. Paietta, Gerard Lozanski, Adam C. Seegmiller, Bruce W. Greig, Aaron C. Shaver, Lata Mukundan, Howard R. Higley, Caroline C. Sigman, Gary Kelloff, J. Milburn Jessup, Michael J. Borowitz

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Minimal residual disease (MRD) in B lymphoblastic leukemia (B-ALL) by flow cytometry is an established prognostic factor used to adjust treatment in most pediatric therapeutic protocols. MRD in B-ALL has been standardized by the Children's Oncology Group (COG) in North America, but not routine clinical labs. The Foundation for National Institutes of Health sought to harmonize MRD measurement among COG, oncology groups, academic, community and government, laboratories. Methods: Listmode data from post-induction marrows were distributed from a reference lab to seven different clinical FCM labs with variable experience in B-ALL MRD. Labs were provided with the COG protocol. Files from 15 cases were distributed to the seven labs. Educational sessions were implemented, and 10 more listmode file cases analyzed. Results: Among 105 initial challenges, the overall discordance rate was 26%. In the final round, performance improved considerably; out of 70 challenges, there were five false positives and one false negative (9% discordance), and no quantitative discordance. Four of six deviations occurred in a single lab. Three samples with hematogones were still misclassified as MRD. Conclusions: Despite the provision of the COG standardized analysis protocol, even experienced laboratories require an educational component for B-ALL MRD analysis by FCM. Recognition of hematogones remains challenging for some labs when using the COG protocol. The results from this study suggest that dissemination of MRD testing to other North American laboratories as part of routine clinical management of B-ALL is possible but requires additional educational components to complement standardized methodology.

Original languageEnglish (US)
JournalCytometry Part B - Clinical Cytometry
DOIs
StateAccepted/In press - 2017

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Residual Neoplasm
Education
National Institutes of Health (U.S.)
North America
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Flow Cytometry
Bone Marrow
Pediatrics
Therapeutics

Keywords

  • Minimal residual disease

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

A QA program for MRD testing demonstrates that systematic education can reduce discordance among experienced interpreters. / Keeney, Michael; Wood, Brent L.; Hedley, Benjamin D.; Digiuseppe, Joseph A.; Stetler-Stevenson, Maryalice; Paietta, Elisabeth M.; Lozanski, Gerard; Seegmiller, Adam C.; Greig, Bruce W.; Shaver, Aaron C.; Mukundan, Lata; Higley, Howard R.; Sigman, Caroline C.; Kelloff, Gary; Jessup, J. Milburn; Borowitz, Michael J.

In: Cytometry Part B - Clinical Cytometry, 2017.

Research output: Contribution to journalArticle

Keeney, M, Wood, BL, Hedley, BD, Digiuseppe, JA, Stetler-Stevenson, M, Paietta, EM, Lozanski, G, Seegmiller, AC, Greig, BW, Shaver, AC, Mukundan, L, Higley, HR, Sigman, CC, Kelloff, G, Jessup, JM & Borowitz, MJ 2017, 'A QA program for MRD testing demonstrates that systematic education can reduce discordance among experienced interpreters', Cytometry Part B - Clinical Cytometry. https://doi.org/10.1002/cyto.b.21528
Keeney, Michael ; Wood, Brent L. ; Hedley, Benjamin D. ; Digiuseppe, Joseph A. ; Stetler-Stevenson, Maryalice ; Paietta, Elisabeth M. ; Lozanski, Gerard ; Seegmiller, Adam C. ; Greig, Bruce W. ; Shaver, Aaron C. ; Mukundan, Lata ; Higley, Howard R. ; Sigman, Caroline C. ; Kelloff, Gary ; Jessup, J. Milburn ; Borowitz, Michael J. / A QA program for MRD testing demonstrates that systematic education can reduce discordance among experienced interpreters. In: Cytometry Part B - Clinical Cytometry. 2017.
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title = "A QA program for MRD testing demonstrates that systematic education can reduce discordance among experienced interpreters",
abstract = "Background: Minimal residual disease (MRD) in B lymphoblastic leukemia (B-ALL) by flow cytometry is an established prognostic factor used to adjust treatment in most pediatric therapeutic protocols. MRD in B-ALL has been standardized by the Children's Oncology Group (COG) in North America, but not routine clinical labs. The Foundation for National Institutes of Health sought to harmonize MRD measurement among COG, oncology groups, academic, community and government, laboratories. Methods: Listmode data from post-induction marrows were distributed from a reference lab to seven different clinical FCM labs with variable experience in B-ALL MRD. Labs were provided with the COG protocol. Files from 15 cases were distributed to the seven labs. Educational sessions were implemented, and 10 more listmode file cases analyzed. Results: Among 105 initial challenges, the overall discordance rate was 26{\%}. In the final round, performance improved considerably; out of 70 challenges, there were five false positives and one false negative (9{\%} discordance), and no quantitative discordance. Four of six deviations occurred in a single lab. Three samples with hematogones were still misclassified as MRD. Conclusions: Despite the provision of the COG standardized analysis protocol, even experienced laboratories require an educational component for B-ALL MRD analysis by FCM. Recognition of hematogones remains challenging for some labs when using the COG protocol. The results from this study suggest that dissemination of MRD testing to other North American laboratories as part of routine clinical management of B-ALL is possible but requires additional educational components to complement standardized methodology.",
keywords = "Minimal residual disease",
author = "Michael Keeney and Wood, {Brent L.} and Hedley, {Benjamin D.} and Digiuseppe, {Joseph A.} and Maryalice Stetler-Stevenson and Paietta, {Elisabeth M.} and Gerard Lozanski and Seegmiller, {Adam C.} and Greig, {Bruce W.} and Shaver, {Aaron C.} and Lata Mukundan and Higley, {Howard R.} and Sigman, {Caroline C.} and Gary Kelloff and Jessup, {J. Milburn} and Borowitz, {Michael J.}",
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T1 - A QA program for MRD testing demonstrates that systematic education can reduce discordance among experienced interpreters

AU - Keeney, Michael

AU - Wood, Brent L.

AU - Hedley, Benjamin D.

AU - Digiuseppe, Joseph A.

AU - Stetler-Stevenson, Maryalice

AU - Paietta, Elisabeth M.

AU - Lozanski, Gerard

AU - Seegmiller, Adam C.

AU - Greig, Bruce W.

AU - Shaver, Aaron C.

AU - Mukundan, Lata

AU - Higley, Howard R.

AU - Sigman, Caroline C.

AU - Kelloff, Gary

AU - Jessup, J. Milburn

AU - Borowitz, Michael J.

PY - 2017

Y1 - 2017

N2 - Background: Minimal residual disease (MRD) in B lymphoblastic leukemia (B-ALL) by flow cytometry is an established prognostic factor used to adjust treatment in most pediatric therapeutic protocols. MRD in B-ALL has been standardized by the Children's Oncology Group (COG) in North America, but not routine clinical labs. The Foundation for National Institutes of Health sought to harmonize MRD measurement among COG, oncology groups, academic, community and government, laboratories. Methods: Listmode data from post-induction marrows were distributed from a reference lab to seven different clinical FCM labs with variable experience in B-ALL MRD. Labs were provided with the COG protocol. Files from 15 cases were distributed to the seven labs. Educational sessions were implemented, and 10 more listmode file cases analyzed. Results: Among 105 initial challenges, the overall discordance rate was 26%. In the final round, performance improved considerably; out of 70 challenges, there were five false positives and one false negative (9% discordance), and no quantitative discordance. Four of six deviations occurred in a single lab. Three samples with hematogones were still misclassified as MRD. Conclusions: Despite the provision of the COG standardized analysis protocol, even experienced laboratories require an educational component for B-ALL MRD analysis by FCM. Recognition of hematogones remains challenging for some labs when using the COG protocol. The results from this study suggest that dissemination of MRD testing to other North American laboratories as part of routine clinical management of B-ALL is possible but requires additional educational components to complement standardized methodology.

AB - Background: Minimal residual disease (MRD) in B lymphoblastic leukemia (B-ALL) by flow cytometry is an established prognostic factor used to adjust treatment in most pediatric therapeutic protocols. MRD in B-ALL has been standardized by the Children's Oncology Group (COG) in North America, but not routine clinical labs. The Foundation for National Institutes of Health sought to harmonize MRD measurement among COG, oncology groups, academic, community and government, laboratories. Methods: Listmode data from post-induction marrows were distributed from a reference lab to seven different clinical FCM labs with variable experience in B-ALL MRD. Labs were provided with the COG protocol. Files from 15 cases were distributed to the seven labs. Educational sessions were implemented, and 10 more listmode file cases analyzed. Results: Among 105 initial challenges, the overall discordance rate was 26%. In the final round, performance improved considerably; out of 70 challenges, there were five false positives and one false negative (9% discordance), and no quantitative discordance. Four of six deviations occurred in a single lab. Three samples with hematogones were still misclassified as MRD. Conclusions: Despite the provision of the COG standardized analysis protocol, even experienced laboratories require an educational component for B-ALL MRD analysis by FCM. Recognition of hematogones remains challenging for some labs when using the COG protocol. The results from this study suggest that dissemination of MRD testing to other North American laboratories as part of routine clinical management of B-ALL is possible but requires additional educational components to complement standardized methodology.

KW - Minimal residual disease

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