Startseite An internal validation approach and quality control on hematopoietic chimerism testing after allogeneic hematopoietic cell transplantation
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An internal validation approach and quality control on hematopoietic chimerism testing after allogeneic hematopoietic cell transplantation

  • Miguel Waterhouse EMAIL logo , Regina Kunzmann , Marta Torres , Hartmut Bertz und Juergen Finke
Veröffentlicht/Copyright: 25. Juli 2012
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 51 Heft 2

Abstract

Background: Hematopoietic chimerism analysis is important in the follow-up of patients undergoing allogeneic stem cell transplantation. PCR of short tandem repeats is mainly used for monitoring chimerism after transplantation. Validation studies and precision of assay’s performance with respect to different mixed chimerism stages is not fully addressed. The aim of the present study was to assess the impact of several microsatellite analytical parameters in the quantification of hematopoietic chimerism after allogeneic hematopoietic stem cell transplantation and to analyze the overall analytical process through the application of internal quality control procedures.

Methods: Artificial DNA mixtures prepared in known proportions and patients samples were analyzed using three microsatellites, together with amplification of amelogenin gene and fluorescence in situ hybridization (FISH) for X and Y chromosomes. Limit of detection, analytical and clinical sensitivity, stochastic threshold and precision profiling was established. Levey-Jennings charts and Westgard rules were applied for quality control evaluation.

Results: Analytical and clinical sensitivity of the microsatellite markers was between 0.5% and 1.6%. Amelogenin detection and FISH for X and Y chromosomes showed a similar sensitivity. Severe allelic imbalance resulted in up to 50% difference between the calculated and corrected mixed chimerism. Systematic errors were identified using Levey-Jennings charts and Westgard rules.

Conclusions: Analysis of hematopoietic chimerism performance is a critical step to better understand potential intrinsic errors that may impact the final hematopoietic chimerism results. Implementing quality control tools, such as Levey-Jennings charts together with Westgard rules can identify systematic and random errors so corrective actions can be performed.

Keywords: allogeneic hematopoietic cell transplantation; hematopoietic chimerism
Corresponding author: Miguel Waterhouse, Department of Hematology/Oncology, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany Phone: +49 761 2703646, Fax: +49 761 2703582

We are indebted to Prof. Dr. R. Mertelsmann for continuous support and Dr. Milena Pantic for assistance with FISH evaluation. We thank also Ingrid Huber, Sabine Enger and Ewa Samek for excellent technical assistance and the transplantation team at Freiburg University Hospital.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Bader P, Niethammer D, Willasch A, Kreyenberg H, Klingebiel T. How and when should we monitor chimerism after allogeneic stem cell transplantation? Bone Marrow Transplant 2005;35: 107–19.10.1038/sj.bmt.1704715Suche in Google Scholar PubMed

2. Antin JH, Childs R, Filipovich AH, Giralt S, Mackinnon S, Spitzer T, et al. Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings of the International Bone Marrow Transplant Registry and the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2001;7:473–85.10.1053/bbmt.2001.v7.pm11669214Suche in Google Scholar

3. Khan F, Agarwal A, Agarwal S. Significance of chimerism in hematopoietic cell transplantation: new variations on an old theme. Bone Marrow Transplant 2004;34:1–12.10.1038/sj.bmt.1704525Suche in Google Scholar PubMed

4. Choi SJ, Lee KH, Lee JH, Kim S, Chung HJ, Lee JS, et al. Prognostic value of hematopoietic chimerism in patients with acute leukemia after allogeneic bone marrow transplantation: a prospective study. Bone Marrow Transplant 2000;26: 327–32.10.1038/sj.bmt.1702504Suche in Google Scholar PubMed

5. Butler JM, Buel E, Crivellente F, Mc Cord BR. Forensic DNA typing by capillary electrophoresis using the ABI 310 and 3100 genetic analyzers for STR analysis. Electrophoresis 2004;25:1397–412.10.1002/elps.200305822Suche in Google Scholar

6. Lion T. Summary: reports on quantitative analysis of chimerism after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection. Leukemia 2003;17:252–4.10.1038/sj.leu.2402753Suche in Google Scholar PubMed

7. Lion T, Watzinger F, Preuner S, Kreyenberg H, Tilanus M, de Weger R, et al. The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation. Leukemia 2012 April 10 [Epub ahead of print].http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000307650000010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1038/leu.2012.66Suche in Google Scholar

8. Mortera J, Dawid AP, Lauritzen SL. Probabilistic expert systems for DNA mixture profiling. Theor Popul Biol 2003;63:191–205.10.1016/S0040-5809(03)00006-6Suche in Google Scholar PubMed

9. Spyridonidis A, Zeiser R, Wäsch R, Bertz H, Finke J. Capillary electrophoresis for chimerism monitoring by PCR amplification of microsatellite markers after allogeneic hematopoietic cell transplantation. Clin Transplant 2005;19:350–6.10.1111/j.1399-0012.2005.00347.xSuche in Google Scholar PubMed

10. Elmaagacli AH, Becks HW, Beelen DW, Stockova J, Bützler R, Opalka B, et al. Detection of minimal residual disease and persistence of host-type hematopoiesis: a study in 28 patients after sex-mismatched, non-T cell depleted allogeneic bone marrow transplantation for Philadelphia-chromosome positive chronic myelogenous leukemia. Bone Marrow Transplant 1995;16:823–9.Suche in Google Scholar PubMed

11. Kristt D, Klein T. Reliability of quantitative chimerism results: assessment of sample performance using novel parameters. Leukemia 2006;20:1169–72.10.1038/sj.leu.2404191Suche in Google Scholar PubMed

12. Westgard JO, Barry PL, Hunt MR, Groth T. A multi-rule Shewhart chart for quality control in clinical chemistry. Clin Chem 1981;27:493–501.10.1093/clinchem/27.3.493Suche in Google Scholar PubMed

13. Appelbaum FR, Forman SJ, Negrin RS, Blume KG, editors. Thomas hematopoietic cell transplantation, 4th ed. Oxford: Blackwell Publishing, 2009:1043.10.1002/9781444303537Suche in Google Scholar

14. Liang SL, Lin MT, Hafez MJ, Gocke CD, Murphy KM, Sokoll LJ, et al. Application of traditional clinical pathology quality control techniques to molecular pathology. J Mol Diagn 2008;10:142–6.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000253874500005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.2353/jmoldx.2008.070123Suche in Google Scholar PubMed PubMed Central

15. Baron F, Baker JE, Storb R, Gooley TA, Sandmaier BM, Maris MB, et al. Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 2004;104: 2254–62.10.1182/blood-2004-04-1506Suche in Google Scholar PubMed

16. Seong CM, Giralt S, Kantarjian H, Xu J, Swantkowski J, Hayes K, et al. Early detection of relapse by hypermetaphase fluorescence in situ hybridization after allogeneic bone marrow transplantation for chronic myeloid leukemia. J Clin Oncol 2000;18: 1831–6.10.1200/JCO.2000.18.9.1831Suche in Google Scholar PubMed

17. Walsh PS, Erlich HA, Higuchi R. Preferential amplification of alleles: mechanisms and solutions. PCR Methods Appl 1992;1:241–50.10.1101/gr.1.4.241Suche in Google Scholar PubMed

Received: 2012-03-09
Accepted: 2012-06-25
Published Online: 2012-07-25
Published in Print: 2013-02-01

©2013 by Walter de Gruyter Berlin Boston

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https://doi.org/10.1515/cclm-2012-0230
Schlagwörter für diesen Artikel
allogeneic hematopoietic cell transplantation; hematopoietic chimerism

Artikel in diesem Heft

  1. Letters to the Editor
  2. Performance evaluation of three different immunoassays for detection of antibodies to hepatitis B core
  3. Serum homocysteine concentrations in Chinese children with autism
  4. Interchangeability of venous and capillary HbA1c results is affected by oxidative stress
  5. Interference of hemoglobin (Hb) N-Baltimore on measurement of HbA1c using the HA-8160 HPLC method
  6. First human isolate of Mycobacterium madagascariense in the sputum of a patient with tracheobronchitis
  7. Protein S and protein C measurements should not be undertaken during vitamin K antagonist therapy
  8. α2-HS glycoprotein is an essential component of cryoglobulin associated with chronic hepatitis C
  9. An unusual interference in CK MB assay caused by a macro enzyme creatine phosphokinase (CK) type 2 in HIV-infected patients
  10. An automated technique for the measurement of the plasma glutathione reductase activity and determination of reference limits for a healthy population
  11. Is osteopontin stable in plasma and serum?
  12. Evidence-based approach to reducing perceived wasteful practices in laboratory medicine
  13. Masthead
  14. Masthead
  15. Editorials
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  17. Lessons from controversy: biomarkers evaluation
  18. Commercial immunoassays in biomarkers studies: researchers beware!1)
  19. Trials and tribulations in lupus anticoagulant testing
  20. Reviews
  21. Mass spectrometry: a revolution in clinical microbiology?
  22. Chronic Chagas disease: from basics to laboratory medicine
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  24. Shop for quality or quantity? Volumes and costs in clinical laboratories
  25. Minor improvement of venous blood specimen collection practices in primary health care after a large-scale educational intervention
  26. Evaluation of high resolution gel β2-transferrin for detection of cerebrospinal fluid leak
  27. Serum kallikrein-8 correlates with skin activity, but not psoriatic arthritis, in patients with psoriatic disease
  28. Soluble urokinase plasminogen activator receptor (suPAR) in the assessment of inflammatory activity of rheumatoid arthritis patients in remission
  29. Bone mass density selectively correlates with serum markers of oxidative damage in post-menopausal women
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  44. Comparison of diagnostic and prognostic performance of two assays measuring thymidine kinase 1 activity in serum of breast cancer patients
  45. Evaluation of the BRAHMS Kryptor® Thyroglobulin Minirecovery Test in patients with differentiated thyroid carcinoma
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