Startseite Comparison of BCR-ABL1 quantification in peripheral blood and bone marrow using an International Scale-standardized assay for assessment of deep molecular response in chronic myeloid leukemia
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Comparison of BCR-ABL1 quantification in peripheral blood and bone marrow using an International Scale-standardized assay for assessment of deep molecular response in chronic myeloid leukemia

  • Georg Greiner ORCID logo , Franz Ratzinger , Michael Gurbisz , Nadine Witzeneder , Hossein Taghizadeh , Sebastian G.K. Mustafa , Gerlinde Mitterbauer-Hohendanner , Harald Esterbauer , Christine Mannhalter , Wolfgang R. Sperr , Peter Valent und Gregor Hoermann EMAIL logo
Veröffentlicht/Copyright: 22. Februar 2020
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 58 Heft 8

Abstract

Background

Monitoring of molecular response (MR) using quantitative polymerase chain reaction (PCR) for BCR-ABL1 is a pivotal tool for guiding tyrosine kinase inhibitor therapy and the long-term follow-up of patients with chronic myeloid leukemia (CML). Results of MR monitoring are standardized according to the International Scale (IS), and specific time-dependent molecular milestones for definition of optimal response and treatment failure have been included in treatment recommendations. The common practice to use peripheral blood (PB) instead of bone marrow (BM) aspirate to monitor the MR monitoring in CML has been questioned. Some studies described differences between BCR-ABL1 levels in paired PB and BM specimens.

Methods

We examined 631 paired PB and BM samples from 283 CML patients in a retrospective single-center study using an IS normalized quantitative reverse transcription (qRT)-PCR assay for quantification of BCR-ABL1IS.

Results

A good overall concordance of BCR-ABL1IS results was found, a systematic tendency towards higher BCR-ABL1IS levels in PB was observed in samples of CML patients in a major MR. This difference was most pronounced in patients treated with imatinib for at least 1 year. Importantly, the difference resulted in a significantly lower rate of deep MR when BCR-ABL1IS was assessed in the PB compared to BM aspirates.

Conclusions

In summary, our data suggest that the classification of deep MR in patients with CML is more stringent in PB than in BM. Our study supports the current practice to primarily use PB for long-term molecular follow-up monitoring in CML.

Keywords: BCR-ABL1; chronic myeloid leukemia; deep molecular response; quantitative PCR
Corresponding author: Gregor Hoermann, MD, PhD, Department of Laboratory Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria, Phone: +43-1-40400-53590, Fax: +43-1-40400-53890

Acknowledgments

The authors thank Jana Strasakova (Department of Laboratory Medicine, Medical University of Vienna) for technical support.

  1. Author contributions: G.G., M.G., N.W., S.M.H.T.W., S.G.K.M, G.M.-H., C.M., and G.H. performed molecular tests and analyzed the data. G.G., H.E., W.R.S., P.V., and G.H. obtained and analyzed clinical data. G.G., F.R., and W.R.S. performed statistical analyses. G.G., P.V., and G.H. designed the study and wrote the paper. All authors revised and approved the manuscript.

  2. Research funding: This study was supported by the Austria Science Fund (FWF) project P26079-B13, the SFB projects Funder Id: http://dx.doi.org/10.13039/501100002428, F4701-B20 and F4704-B20, and the Medical-Scientific Fund of the Mayor of Vienna.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

  6. Conflict of interest: P.V. served as a consultant in a global Novartis trial investigating the effects of midostaurin in patients with advanced systemic mastocytosis and received honoraria and research grants from Novartis, Blueprint, Pfizer, Ariad, Incyte, Celgene, and Deciphera. W.R.S. received honoraria from Novartis. G.H. received honoraria and research grants from Novartis. The authors declare no other competing financial interests.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-1172).

Received: 2019-11-12
Accepted: 2020-01-23
Published Online: 2020-02-22
Published in Print: 2020-07-28

©2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

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  2. Editorial
  3. Quality controls for serology: an unfinished agenda
  4. A modern and pragmatic definition of Laboratory Medicine
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https://doi.org/10.1515/cclm-2019-1172
Schlagwörter für diesen Artikel
BCR-ABL1; chronic myeloid leukemia; deep molecular response; quantitative PCR

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Quality controls for serology: an unfinished agenda
  4. A modern and pragmatic definition of Laboratory Medicine
  5. Reviews
  6. Blood biochemical characteristics of patients with coronavirus disease 2019 (COVID-19): a systemic review and meta-analysis
  7. ISO/TS 20914:2019 – a critical commentary
  8. Mini Review
  9. Reporting of D-dimer data in COVID-19: some confusion and potential for misinformation
  10. Opinion Paper
  11. Implementation of metrological traceability in laboratory medicine: where we are and what is missing
  12. IFCC Recommendation
  13. Recommendation for performance verification of patient-based real-time quality control
  14. Genetics and Molecular Diagnostics
  15. Comparison of BCR-ABL1 quantification in peripheral blood and bone marrow using an International Scale-standardized assay for assessment of deep molecular response in chronic myeloid leukemia
  16. General Clinical Chemistry and Laboratory Medicine
  17. Risk assessment of the total testing process based on quality indicators with the Sigma metrics
  18. Determination of hemolysis cut-offs for biochemical and immunochemical analytes according to their value
  19. A computer model for professional competence assessment according to ISO 15189
  20. Traceability validation of six enzyme measurements on the Abbott Alinity c analytical system
  21. Evaluating the need for free glycerol blanking for serum triglyceride measurements at Charlotte Maxeke Johannesburg Academic Hospital
  22. Challenges of LC-MS/MS ethyl glucuronide analysis in abstinence monitoring of liver transplant candidates
  23. Changes in the result of antinuclear antibody immunofluorescence assay on HEp-2 cells reflect disease activity status in systemic lupus erythematosus
  24. Reference Values and Biological Variations
  25. Long-term biological variation estimates of 13 hematological parameters in healthy Chinese subjects
  26. Age-specific reference values improve the diagnostic performance of AMH in polycystic ovary syndrome
  27. Establishment of reference intervals for immunoassay analytes of adult population in Saudi Arabia
  28. Hematology and Coagulation
  29. Total haemoglobin – a reference measuring system for improvement of standardisation
  30. Laboratory testing for activated protein C resistance: rivaroxaban induced interference and a comparative evaluation of andexanet alfa and DOAC Stop to neutralise interference
  31. Cancer Diagnostics
  32. Identification of a four-gene methylation biomarker panel in high-grade serous ovarian carcinoma
  33. Performance comparison of two next-generation sequencing panels to detect actionable mutations in cell-free DNA in cancer patients
  34. Diabetes
  35. Availability and analytical quality of hemoglobin A1c point-of-care testing in general practitioners’ offices are associated with better glycemic control in type 2 diabetes
  36. Infectious Diseases
  37. Validation of a chemiluminescent assay for specific SARS-CoV-2 antibody
  38. Dynamic profile and clinical implications of hematological parameters in hospitalized patients with coronavirus disease 2019
  39. Does a change in quality control results influence the sensitivity of an anti-HCV test?
  40. Letters to the Editor
  41. Variability between testing methods for SARS-CoV-2 nucleic acid detection 16 days post-discharge: a case report
  42. L-index, more than a screening tool for hypertriglyceridemia
  43. Neutralization of biotin interference: preliminary evaluation of the VeraTest Biotin™, VeraPrep Biotin™ and BioT-Filter®
  44. Counting and reporting band count is unreliable practice due to the high inter-observer variability
  45. Cigarette smoking prior to blood sampling acutely affects serum levels of the chronic obstructive pulmonary disease biomarker surfactant protein D
  46. How reliable is the detection of anti-mitochondrial antibodies on murine triple-tissue?
  47. Further advices on measuring lipoprotein(a) for reducing the residual cardiovascular risk on statin therapy
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