Minimal residual disease (MRD) in non-Hodgkin lymphomas: Interlaboratory reproducibility on marrow samples with very low levels of disease within the FIL (Fondazione Italiana Linfomi) MRD Network.
Bone Marrow
/ pathology
Bone Marrow Examination
/ standards
Clone Cells
Gene Rearrangement, B-Lymphocyte, Heavy Chain
Genes, Immunoglobulin
Genes, bcl-2
High-Throughput Nucleotide Sequencing
Humans
Immunoglobulin Heavy Chains
/ genetics
Immunoglobulin Variable Region
/ genetics
Italy
/ epidemiology
Laboratory Proficiency Testing
Lymphoma, Non-Hodgkin
/ genetics
Neoplasm, Residual
Oncogene Proteins, Fusion
/ analysis
Polymerase Chain Reaction
/ methods
Proto-Oncogene Proteins c-bcl-2
/ genetics
Quality Assurance, Health Care
Reproducibility of Results
Translocation, Genetic
FIL
MRD
PCR
PNQ samples
non-Hodgkin lymphoma
Journal
Hematological oncology
ISSN: 1099-1069
Titre abrégé: Hematol Oncol
Pays: England
ID NLM: 8307268
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
17
05
2019
revised:
08
07
2019
accepted:
11
07
2019
pubmed:
22
7
2019
medline:
20
11
2019
entrez:
21
7
2019
Statut:
ppublish
Résumé
In 2009, the four laboratories of the Fondazione Italiana Linfomi (FIL) minimal residual disease (MRD) Network started a collaborative effort to harmonize and standardize their methodologies at the national level, performing quality control (QC) rounds for follicular lymphoma (FL) and mantle cell lymphoma (MCL) MRD assessment. In 16 QC rounds between 2010 and 2017, the four laboratories received 208 bone marrow (BM) samples (126 FL; 82 MCL); 187 were analyzed, according to the EuroMRD Consortium guidelines, by both nested (NEST) polymerase chain reaction (PCR) and real-time quantitative (RQ) PCR for BCL2/IGH MBR or IGHV rearrangements. Here, we aimed at analyzing the samples that challenged the interlaboratory reproducibility and data interpretation. Overall, 156/187 BM samples (83%) were concordantly classified as NEST+/RQ+ or NEST-/RQ- by all the four laboratories. The remaining 31 samples (17%) resulted alternatively positive and negative in the interlaboratory evaluations, independently of the method and the type of rearrangement, and were defined "borderline" (brd) samples: 12 proved NEST brd/RQ brd, 7 NEST-/RQ brd, 10 NEST brd/RQ positive not quantifiable (PNQ), and 2 NEST brd/RQ-. Results did not change even increasing the number of replicates/sample. In 6/31 brd samples, droplet digital PCR (ddPCR) was tested and showed no interlaboratory discordance. Despite the high interlaboratory reproducibility in the MRD analysis obtained and maintained by the QC round strategy, samples with the lowest MRD levels can still represent a challenge: 17% (31/187) of our samples showed discordant results in interlaboratory assessments, with 6.4% (12/187) remained brd even applying the two methods. Thus, although representing a minority, brd samples are still problematic, especially when a clinically oriented interpretation of MRD results is required. Alternative, novel methods such as ddPCR and next-generation sequencing have the potential to overcome the current limitations.
Substances chimiques
BCL2 protein, human
0
Immunoglobulin Heavy Chains
0
Immunoglobulin Variable Region
0
Oncogene Proteins, Fusion
0
Proto-Oncogene Proteins c-bcl-2
0
Types de publication
Comparative Study
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
368-374Subventions
Organisme : Fondazione DaRosa, Torino, Italy
Organisme : Fondazione CRT, Torino, Italy
ID : 2016.0677
Organisme : Fondazione CRT, Torino, Italy
ID : 2018.1284
Organisme : Fondazione Neoplasie Del Sangue (Fo.Ne.Sa), Torino, Italy
Organisme : Università degli Studi di Torino, Italy
ID : Fondi di Ricerca Locale
Organisme : Fondi di Ricerca Locale
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : MCO-10007
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : N° 21198
Informations de copyright
© 2019 John Wiley & Sons, Ltd.
Références
Van der Velden VH, Hochhaus A, Cazzaniga G, Szczepanski T, Gabert J, Van Dongen JJ. Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects. Leukemia. 2003;17(6):1013-1034.
Conter V, Bartram CR, Valsecchi MG, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115(16):3206-3214.
Brüggemann M, Raff T, Flohr T, et al. German Multicenter Study Group for Adult Acute Lymphoblastic LeukemiaClinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006;107(3):1116-1123.
Pott C, Hoster E, Delfau-Larue MH, et al. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood. 2010;115(16):3215-3223.
Corradini P, Ladetto M, Zallio F, et al. Long-term follow-up of indolent lymphoma patients treated with high-dose sequential chemotherapy and autografting: evidence that durable molecular and clinical remission frequently can be attained only in follicular subtypes. J Clin Oncol. 2004;22(8):1460-1468.
Ladetto M, De Marco F, Benedetti F, et al. Gruppo Italiano Trapianto di Midollo Osseo (GITMO); Intergruppo Italiano Linfomi (IIL)Prospective, multicenter randomized GITMO/IIL trial comparing in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood. 2008;111(8):4004-4013.
Ladetto M, Lobetti-Bodoni C, Mantoan B, et al. Fondazione Italiana LinfomiPersistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program. Blood. 2013;122(23):3759-3766.
Galimberti S, Luminari S, Ciabatti E, et al. Minimal residual disease after conventional treatment significantly impacts on progression-free survival of patients with follicular lymphoma: the FIL FOLL05 trial. Clin Cancer Res. 2014;20(24):6398-6405.
Ladetto M, Buske C, Hutchings M, et al. & the ESMO Lymphoma Consensus Conference Panel MembersESMO consensus conference on malignant lymphoma: general perspectives and recommendations for prognostic tools in mature B-cell lymphomas and chronic lymphocytic leukaemia. Ann Oncol. 2016;27(12):2149-2160.
Pott C, Brüggemann M, Ritgen M, van der Velden VH, van Dongen JJ, Kneba M. MRD detection in B-cell non-Hodgkin lymphomas using Ig gene rearrangements and chromosomal translocations as targets for real-time quantitative PCR. Methods Mol Biol. 2013;971:175-200.
van der Velden VH, Cazzaniga G, Schrauder A, et al. European Study Group on MRD detection in ALL (ESG-MRD-ALL)Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia. 2007;21(4):604-611.
Kotrova M, Muzikova K, Mejstrikova E, et al. The predictive strength of next-generation sequencing MRD detection for relapse compared with current methods in childhood ALL. Blood. 2015;126(8):1045-1047.
Drandi D, Alcantara M, Barbero D, et al. QPCR, MFC and ddPCR: comparison on MRD samples from three prospective trials of the European MCL network. 24th Congress of the European Hematology Association, Amsterdam, June 13-16, 2019. HemaSphere. 2019;3(Suppl1):599.
Gribben JG, Neuberg D, Freedman AS, et al. Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma. Blood. 1993;81(12):3449-3457.
Ladetto M, Sametti S, Donovan JW, et al. A validated real-time quantitative PCR approach shows a correlation between tumor burden and successful ex vivo purging in follicular lymphoma patients. Exp Hematol. 2001;29(2):183-193.
Cavalli M, De Novi LA, Della Starza I, et al. Comparative analysis between RQ-PCR and digital droplet PCR of BCL2/IGH gene rearrangement in the peripheral blood and bone marrow of early stage follicular lymphoma. Br J Haematol. 2017;177(4):588-596.
Drandi D, Kubiczkova-Besse L, Ferrero S, et al. Minimal residual disease detection by droplet digital PCR in multiple myeloma, mantle cell lymphoma, and follicular lymphoma: a comparison with real-time PCR. J Mol Diagn. 2015;17(6):652-660.
Della Starza I, Nunes V, Cavalli M, et al. Comparative analysis between RQ-PCR and digital-droplet-PCR of immunoglobulin/T-cell receptor gene rearrangements to monitor minimal residual disease in acute lymphoblastic leukaemia. Br J Haematol. 2016;174(4):541-549.
van Dongen JJ, Langerak AW, Brüggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia. 2003;17(12):2257-2317.
Ladetto M, Donovan JW, Harig S, et al. Real time polymerase chain reaction of immunoglobulin rearrangements for quantitative evaluation of minimal residual disease in multiple myeloma. Biol Blood Marrow Transplant. 2000;6(3):241-253.
Donovan JW, Ladetto M, Zou G, et al. Immunoglobulin heavy-chain consensus probes for real-time PCR quantification of residual disease in acute lymphoblastic leukemia. Blood. 2000;95(8):2650-2658.
Della Starza I, Cavalli M, Del Giudice I, et al. Comparison of two real-time quantitative polymerase chain reaction strategies for minimal residual disease evaluation in lymphoproliferative disorders: correlation between immunoglobulin gene mutation load and real-time quantitative polymerase chain reaction performance. Hematol Oncol. 2014;32(3):133-138.
Lobetti-Bodoni C, Mantoan B, Monitillo L, et al. Clinical implications and prognostic role of minimal residual disease detection in follicular lymphoma. Ther Adv Hematol. 2013;4(3):189-198.
Gibson U, Heid C, Williams P. A novel method for real time quantitative RT-PCR. Genome Res. 1996;6(10):995-1001.
Brüggemann M, Schrauder A, Raff T, et al. European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL); International Berlin-Frankfurt-Münster Study Group (I-BFM-SG)Standardized MRD quantification in European ALL trials: Proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, September 18-20, 2008. Leukemia. 2010;24(3):521-535.
Ferrero S, Barbero D, Lo Schirico M, et al. Comprehensive minimal residual disease (MRD) analysis of the Fondazione Italiana Linfomi (FIL) MCL0208 clinical trial for younger patients with mantle cell lymphoma: a kinetic model ensures a more refined risk stratification. 60th ASH Annual Meeting and Exposition, San Diego, December 1-4, 2018. Blood. 2018;132(Suppl1):920.
Guerrini F, Paolicchi M, Ghio F, et al. The droplet digital PCR: a new valid molecular approach for the assessment of BRAF V600E mutation in hairy cell leukemia. Front Pharmacol. 2016;7:363.
Della Starza I, Del Giudice I, Menale L, et al. Minimal residual disease (MRD) detection by digital-droplet-pcr (ddPCR) in lymphoid malignancies. XV Congress of the Italian Society Of Experimental Hematology, Rimini, Italy, October 18-20, 2018. Haematologica. 2018;103:S1-S129.
Sanders R, Huggett JF, Bushell CA, Cowen S, Scott DJ, Foy CA. Evaluation of digital PCR for absolute DNA quantification. Anal Chem. 2011;83(17):6474-6484.
Whale AS, Huggett JF, Cowen S, et al. Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation. Nucleic Acids Res. 2012;40(11):e82.
Hindson CM, Chevillet JR, Briggs HA, et al. Absolute quantification by droplet digital PCR versus analog real-time PCR. Nat Methods. 2013;10(10):1003-1005.
Pulsoni A, Della Starza I, Cappelli LV, et al. Minimal residual disease monitoring in early stage follicular lymphoma can predict prognosis and drive treatment with rituximab after radiotherapy. Br J Haematol. 2019. in press
Faham M, Zheng J, Moorhead M, et al. Deep sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2012;120(26):5173-5180.
Logan AC, Zhang B, Narasimhan B, et al. Minimal residual disease quantification using consensus primers and high-throughput IGH sequencing predicts post-transplant relapse in chronic lymphocytic leukemia. Leukemia. 2013;27(8):1659-1665.
Ladetto M, Brüggemann M, Monitillo L, et al. Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders. Leukemia. 2014;28(6):1299-1307.
Kotrova M, van der Velden VHJ, van Dongen JJM, et al. Next-generation sequencing indicates false-positive MRD results and better predicts prognosis after SCT in patients with childhood ALL. Bone Marrow Transplant. 2017;52(7):962-968.
Della Starza I, De Novi LA, Santoro A, et al. Comparative analysis between RQ-PCR, digital-droplet-PCR and next-generation-sequencing (NGS) of immunoglobulin/T-cell receptor gene rearrangements to monitor minimal residual disease in adult acute lymphoblastic leukemia patients. 60th ASH Annual Meeting and Exposition, San Diego, December 1-4, 2018. Blood. 2018;132(Suppl1):2828.