Skip to main content

Advertisement

SpringerLink
Log in

Clinician-friendly reports of molecular measurable residual disease monitoring in acute promyelocytic leukemia

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Molecular measurable residual disease (MRD) monitoring based on real-time quantitative reverse transcription PCR (RT-qPCR) plays an important role in acute promyelocytic leukemia (APL) management, but the performance status of clinical reports is unknown. This study focuses on the specific elements in molecular MRD monitoring report and their impact on clinical decision-making. The participating laboratories were asked to submit real and formal clinical reports for mock samples panel with APL clinical case. The MRD-specific elements were analyzed and summarized. The significance of longitudinal MRD monitoring curve and the missing MRD-specific elements for clinical decision-making were assessed. MRD-specific elements were significantly missing in clinical reports. The element “testing results” existed great inconsistencies in the written form of testing items and data. The longitudinal MRD monitoring curve of false-negative or false-positive MRD result was obviously different from all-correct. It not only identified MRD time point of tissue sampling relative to treatment and ensured the reliability of the negative MRD results, but also gave MRD diagnosis, clinical interpretation, and further recommendation. Clinician-friendly reports with MRD-specific elements can better serve clinical practice. The correctly intuitive results and clinically important MRD-specific elements can provide a good description of the reliability and clinical significance of MRD results.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Tallman MS, Kwaan HC (1992) Reassessing the hemostatic disorder associated with acute promyelocytic leukemia. Blood 79(3):543–553

    Article  CAS  PubMed  Google Scholar 

  2. Park JH, Qiao B, Panageas KS, Schymura MJ, Jurcic JG, Rosenblat TL, Altman JK, Douer D, Rowe JM, Tallman MS (2011) Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood 118:1248–1254. https://doi.org/10.1182/blood-2011-04-346437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Grignani F, Ferrucci PF, Testa U, Talamo G, Fagioli M, Alcalay M, Mencarelli A, Grignani F, Peschle C, Nicoletti I, Pelicci PG (1993) The acute promyelocytic leukemia-specific PML-RARα fusion protein inhibits differentiation and promotes survival of myeloid precursor cells. Cell 74(3):423–431

    Article  CAS  PubMed  Google Scholar 

  4. O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, Bhatt V, Bixby D, Blum W, Coutre SE, de Lima M, Fathi AT, Fiorella M, Foran JM, Gore SD, Hall AC, Kropf P, Lancet J, Maness LJ, Marcucci G, Martin MG, Moore JO, Olin R, Peker D, Pollyea DA, Pratz K, Ravandi F, Shami PJ, Stone RM, Strickland SA, Wang ES, Wieduwilt M, Gregory K, Ogba N (2017) Acute myeloid leukemia, version 3.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 15(7):926–957. https://doi.org/10.6004/jnccn.2017.0116

    Article  Google Scholar 

  5. Sanz MA, Grimwade D, Tallman MS, Lowenberg B, Fenaux P, Estey EH, Naoe T, Lengfelder E, Buchner T, Dohner H, Burnett AK, Lo-Coco F (2009) Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 113(9):1875–1891. https://doi.org/10.1182/blood-2008-04-150250

    Article  CAS  PubMed  Google Scholar 

  6. Dayton VJ, McKenna RW, Yohe SL et al (2017) Relapsed acute promyelocytic leukemia lacks “classic” leukemic promyelocyte morphology and can create diagnostic challenges. Am J Clin Pathol 147(1):69–76. https://doi.org/10.1093/ajcp/aqw202

    Article  PubMed  Google Scholar 

  7. Imagawa J (2018) Switching from all-trans retinoic acid to arsenic trioxide for newly diagnosed acute promyelocytic leukemia. Leuk Lymphoma 4:1–3. https://doi.org/10.1080/10428194.2018.1443333

    Article  CAS  Google Scholar 

  8. de Thé H, Chen Z (2010) Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat Rev Cancer 10(11):775–783. https://doi.org/10.1038/nrc2943

    Article  CAS  PubMed  Google Scholar 

  9. Grimwade D, Jovanovic JV, Hills RK, Nugent EA, Patel Y, Flora R, Diverio D, Jones K, Aslett H, Batson E, Rennie K, Angell R, Clark RE, Solomon E, Lo-Coco F, Wheatley K, Burnett AK (2009) Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol 27(22):3650–3658. https://doi.org/10.1200/JCO.2008.20.1533

    Article  CAS  PubMed  Google Scholar 

  10. Albano F, Mestice A, Pannunzio A et al (2006) The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34 CD2 hypergranular (M3) and microgranular (M3v) phenotypes. Haematologica 91(3):311–316

    CAS  PubMed  Google Scholar 

  11. Gabert J, Beillard E, Van der Velden VHJ et al (2003) Standardization and quality control studies of ‘real-time’quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia–a Europe Against Cancer program. Leukemia 17(12):2318–2357. https://doi.org/10.1038/sj.leu.2403135

    Article  CAS  PubMed  Google Scholar 

  12. Østergaard M, Nyvold CG, Jovanovic JV, Andersen MT, Kairisto V, Morgan YG, Tobal K, Pallisgaard N, Özbek U, Pfeifer H, Schnittger S, Grubach L, Larsen JK, Grimwade D, Hokland P (2011) Development of standardized approaches to reporting of minimal residual disease data using a reporting software package designed within the European LeukemiaNet. Leukemia 25(7):1168–1173. https://doi.org/10.1038/leu.2011.69

    Article  PubMed  Google Scholar 

  13. Schuurhuis GJ, Heuser M, Freeman S, Béné MC, Buccisano F, Cloos J, Grimwade D, Haferlach T, Hills RK, Hourigan CS, Jorgensen JL, Kern W, Lacombe F, Maurillo L, Preudhomme C, van der Reijden BA, Thiede C, Venditti A, Vyas P, Wood BL, Walter RB, Döhner K, Roboz GJ, Ossenkoppele GJ (2018) Minimal/measurable residual disease in AML: consensus document from ELN MRD Working Party. Blood 131(12):1275–1291. https://doi.org/10.1182/blood-2017-09-801498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Beillard E, Pallisgaard N, Van der Velden VHJ et al (2003) Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR)–a Europe against cancer program. Leukemia 17(12):2474–2486. https://doi.org/10.1038/sj.leu.2403136

    Article  CAS  PubMed  Google Scholar 

  15. Scheuner MT, Hilborne L, Brown J, Lubin, for the members of the RAND IM (2012) A report template for molecular genetic tests designed to improve communication between the clinician and laboratory. Genet Test Mol Biomarkers 16(7):761–769. https://doi.org/10.1089/gtmb.2011.0328

    Article  PubMed  Google Scholar 

  16. Deans Z, Ahn JW, Bergbaum A, et al. Best practice guidelines for internal quality control in genetic laboratories. 2015

    Google Scholar 

  17. Gulley ML, Braziel RM, Halling KC et al (2007) Clinical laboratory reports in molecular pathology. Arch Pathol Lab Med 131(6):852–863. https://doi.org/10.1043/1543-2165(2007)131[852:CLRIMP]2.0.CO;2

    Article  CAS  PubMed  Google Scholar 

  18. Haga SB, Mills R, Pollak KI, Rehder C, Buchanan AH, Lipkus IM, Crow JH, Datto M (2014) Developing patient-friendly genetic and genomic test reports: formats to promote patient engagement and understanding. Genome Med 6(7):58. https://doi.org/10.1186/s13073-014-0058-6

    Article  PubMed  PubMed Central  Google Scholar 

  19. Claustres M, Kožich V, Dequeker E et al (2014) Recommendations for reporting results of diagnostic genetic testing (biochemical, cytogenetic and molecular genetic). Eur J Hum Genet 22(2):160–170. https://doi.org/10.1038/ejhg.2013.125

    Article  PubMed  Google Scholar 

  20. Dorschner MO, Amendola LM, Shirts BH, Kiedrowski L, Salama J, Gordon AS, Fullerton SM, Tarczy-Hornoch P, Byers PH, Jarvik GP (2014) Refining the structure and content of clinical genomic reports[C]. Am J Med Genet C: Semin Med Genet 166(1):85–92. https://doi.org/10.1002/ajmg.c.31395

    Article  Google Scholar 

  21. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Löwenberg B, Bloomfield CD (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447. https://doi.org/10.1182/blood-2016-08-733196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhan S, Li J, Xu R, Wang L, Zhang K, Zhang R (2009) Armored long RNA controls or standards for branched DNA assay for detection of human immunodeficiency virus type. J Clin Microbiol 47(8):2571–2576. https://doi.org/10.1128/JCM.00232-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Foroni L, Wilson G, Gerrard G, Mason J, Grimwade D, White HE, de Castro DG, Austin S, Awan A, Burt E, Clench T, Farruggia J, Hancock J, Irvine AE, Kizilors A, Langabeer S, Milner BJ, Nickless G, Schuh A, Sproul A, Wang L, Wickham C, Cross NCP (2011) Guidelines for the measurement of BCR-ABL1 transcripts in chronic myeloid leukaemia. Br J Haematol 153(2):179–190. https://doi.org/10.1111/j.1365-2141.2011.08603.x

    Article  CAS  PubMed  Google Scholar 

  24. Nagai S, Nannya Y, Arai S, Yoshiki Y, Takahashi T, Kurokawa M (2010) Molecular or cytogenetic monitoring and preemptive therapy for central nervous system relapse of acute promyelocytic leukemia. Haematologica 95(1):169–171. https://doi.org/10.3324/haematol.2009.015545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Dunnen JT, Dalgleish R, Maglott DR et al (2016) HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat 37(6):564–569. https://doi.org/10.1002/humu.22981

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China

    Qisheng Wu, Rui Zhang, Rongxue Peng, Yu Fu, Jiawei Zhang, Kun Chen & Jinming Li

  2. Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China

    Qisheng Wu, Yu Fu, Jiawei Zhang, Kun Chen & Jinming Li

  3. Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, People’s Republic of China

    Qisheng Wu, Rui Zhang, Rongxue Peng, Yu Fu, Jiawei Zhang, Kun Chen & Jinming Li

  4. Division of Pathology and Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, Beijing, People’s Republic of China

    Qisheng Wu

Authors
  1. Qisheng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rongxue Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jiawei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kun Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jinming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jinming Li.

Ethics declarations

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 19 kb)

ESM 2

(XLSX 11 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, Q., Zhang, R., Peng, R. et al. Clinician-friendly reports of molecular measurable residual disease monitoring in acute promyelocytic leukemia. Ann Hematol 98, 2347–2355 (2019). https://doi.org/10.1007/s00277-019-03782-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-019-03782-z

Keywords

Search

Navigation