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Chronic lymphocytic leukemia

Minimal residual disease analysis in chronic lymphocytic leukemia: a way for achieving more personalized treatments

Leukemia volume 32, pages 1307–1316 (2018)Cite this article

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ABSTRACT

Therapeutic approaches for chronic lymphocytic leukemia (CLL) have dramatically changed over the recent past. In parallel, quantification of minimal residual disease (MRD) proved to be an independent prognostic factor for progression-free and overall survival. The European Research Initiative on CLL (ERIC) in collaboration with American and Australasian partners developed harmonised assays that could be applied reproducibly to compare the efficacy of different treatments. The potential for MRD analysis to identify the most effective treatments prior to reaching survival endpoints was recognised by regulatory agencies and approved as an intermediate endpoint for licensure in randomized studies, in Europe. More recently treatment approaches have evolved, in particular with BCL2-pathway inhibitors, so that MRD analysis may be informative for most patients and clinical trials, potentially becoming a tool for managing CLL patients in clinical practice. In the recent past the importance of the type of MRD assay used, the most appropriate timing and compartment to assess for different treatment types have been learnt as we move towards eradicating residual disease beyond the guideline threshold of one cell in ten thousand. Nowadays, MRD assessment in CLL has quickly become an indispensable tool for clinical research and development that promise to change the way we manage our patients in the future.

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References

  1. European Medicines Agency - - Appendix 4 to the guideline on the evaluation of anticancer medicinal products in man - condition specific guidance. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001124.jsp&mid= Accessed 15 May 2017.

  2. Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376:1164–74.

    Article  PubMed  CAS  Google Scholar 

  3. Bosch F, Ferrer A, Villamor N, González M, Briones J, González-Barca E, et al. Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication. Clin Cancer Res J Am Assoc Cancer Res. 2008;14:155–61.

    Article  CAS  Google Scholar 

  4. Bosch F, Abrisqueta P, Villamor N, Terol MJ, González-Barca E, Ferra C, et al. Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia. J Clin Oncol J Am Soc Clin Oncol. 2009;27:4578–84.

    Article  CAS  Google Scholar 

  5. Moreton P, Kennedy B, Lucas G, Leach M, Rassam SMB, Haynes A, et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol J Am Soc Clin Oncol. 2005;23:2971–9.

    Article  CAS  Google Scholar 

  6. Moreno C, Villamor N, Colomer D, Esteve J, Giné E, Muntañola A, et al. Clinical significance of minimal residual disease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia. Blood. 2006;107:4563–9.

    Article  PubMed  CAS  Google Scholar 

  7. Dreger P, Döhner H, Ritgen M, Böttcher S, Busch R, Dietrich S, et al. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010;116:2438–47.

    Article  PubMed  CAS  Google Scholar 

  8. Böttcher S, Ritgen M, Fischer K, Stilgenbauer S, Busch RM, Fingerle-Rowson G, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol J Am Soc Clin Oncol. 2012;30:980–8.

    Article  Google Scholar 

  9. Fischer K, Cramer P, Busch R, Böttcher S, Bahlo J, Schubert J, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol J Am Soc Clin Oncol. 2012;30:3209–16.

    Article  CAS  Google Scholar 

  10. Pettitt AR, Jackson R, Carruthers S, Dodd J, Dodd S, Oates M, et al. Alemtuzumab in combination with methylprednisolone is a highly effective induction regimen for patients with chronic lymphocytic leukemia and deletion of TP53: final results of the national cancer research institute CLL206 trial. J Clin Oncol J Am Soc Clin Oncol. 2012;30:1647–55.

    Article  CAS  Google Scholar 

  11. Abrisqueta P, Villamor N, Terol MJ, González-Barca E, González M, Ferrà C, et al. Rituximab maintenance after first-line therapy with rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) for chronic lymphocytic leukemia. Blood. 2013;122:3951–9. https://doi.org/10.1182/blood-2013-05-502773

    Article  PubMed  CAS  Google Scholar 

  12. Strati P, Keating MJ, O’Brien SM, Burger J, Ferrajoli A, Jain N, et al. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL. Blood. 2014;123:3727–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Santacruz R, Villamor N, Aymerich M, Martínez-Trillos A, López C, Navarro A, et al. The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy. Haematologica. 2014;99:873–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Dimier N, Delmar P, Ward C, Morariu-Zamfir R, Fingerle-Rowson G, Bahlo J, et al. A model for predicting effect of treatment on progression-free survival using minimal residual disease as a surrogate endpoint in chronic lymphocytic leukemia. Blood 2018;131:955–962.

  15. Rawstron AC, Villamor N, Ritgen M, Böttcher S, Ghia P, Zehnder JL, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia. 2007;21:956–64.

    Article  PubMed  CAS  Google Scholar 

  16. Rawstron AC, Böttcher S, Letestu R, Villamor N, Fazi C, Kartsios H, et al. Improving efficiency and sensitivity: European Research Initiative in CLL (ERIC) update on the international harmonised approach for flow cytometric residual disease monitoring in CLL. Leukemia. 2013;27:142–9.

    Article  PubMed  CAS  Google Scholar 

  17. Rawstron AC, Fazi C, Agathangelidis A, Villamor N, Letestu R, Nomdedeu J, et al. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study. Leukemia. 2016;30:929–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Borowitz MJ, Wood BL, Devidas M, Loh ML, Raetz EA, Salzer WL, et al. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children’s Oncology Group study AALL0232. Blood. 2015;126:964–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a children’s oncology group study. Blood. 2008;111:5477–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Tam CS, Keating MJ. Chemoimmunotherapy of chronic lymphocytic leukemia. Nat Rev Clin Oncol. 2010;7:521–32.

    Article  PubMed  CAS  Google Scholar 

  21. Lenormand B, Bizet M, Fruchart C, Tilly H, Daliphard S, Thouret F, et al. Residual disease in B-cell chronic lymphocytic leukemia patients and prognostic value. Leukemia. 1994;8:1019–26.

    PubMed  CAS  Google Scholar 

  22. Cabezudo E, Matutes E, Ramrattan M, Morilla R, Catovsky D. Analysis of residual disease in chronic lymphocytic leukemia by flow cytometry. Leukemia. 1997;11:1909–14.

    Article  PubMed  CAS  Google Scholar 

  23. Robertson LE, Huh YO, Butler JJ, Pugh WC, Hirsch-Ginsberg C, Stass S, et al. Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis. Blood. 1992;80:29–36.

    PubMed  CAS  Google Scholar 

  24. Vuillier F, Claisse JF, Vandenvelde C, Travade P, Magnac C, Chevret S, et al. Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements. Leuk Lymphoma. 1992;7:195–204.

    Article  PubMed  CAS  Google Scholar 

  25. Noy A, Verma R, Glenn M, Maslak P, Rahman ZU, Keenan JR, et al. Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol. Blood. 2001;97:1929–36.

    Article  PubMed  CAS  Google Scholar 

  26. Richardson DS, Johnson SA, Hopkins JA, Howe D, Phillips MJ. Absence of minimal residual disease detectable by FACS, Southern blot or PCR in patients with chronic lymphocytic leukaemia treated with fludarabine. Acta Oncol Stockh Swed. 1994;33:627–30.

    Article  CAS  Google Scholar 

  27. Montserrat E. Rituximab in chronic lymphocytic leukemia. Semin Oncol. 2003;30:34–9.

    Article  CAS  PubMed  Google Scholar 

  28. Keating MJ, O’Brien S, Albitar M, Lerner S, Plunkett W, Giles F, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol J Am Soc Clin Oncol. 2005;23:4079–88.

    Article  CAS  Google Scholar 

  29. Provan D, Bartlett-Pandite L, Zwicky C, Neuberg D, Maddocks A, Corradini P, et al. Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation. Blood. 1996;88:2228–35.

    PubMed  CAS  Google Scholar 

  30. van der Velden VHJ, Hochhaus A, Cazzaniga G, Szczepanski T, Gabert J, van Dongen JJM. Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects. Leukemia. 2003;17:1013–34.

    Article  PubMed  CAS  Google Scholar 

  31. Böttcher S, Ritgen M, Pott C, Brüggemann M, Raff T, Stilgenbauer S, et al. Comparative analysis of minimal residual disease detection using four-color flow cytometry, consensus IgH-PCR, and quantitative IgH PCR in CLL after allogeneic and autologous stem cell transplantation. Leukemia. 2004;18:1637–45.

    Article  PubMed  CAS  Google Scholar 

  32. Böttcher S, Stilgenbauer S, Busch R, Brüggemann M, Raff T, Pott C, et al. Standardized MRD flow and ASO IGH RQ-PCR for MRD quantification in CLL patients after rituximab-containing immunochemotherapy: a comparative analysis. Leuk J Leuk Soc Am Leuk Res Fund UK. 2009;23:2007–17.

    Google Scholar 

  33. Arroz M, Came N, Lin P, Chen W, Yuan C, Lagoo A, et al. Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting. Cytom B Clin Cytom. 2016;90:31–9.

    Article  CAS  Google Scholar 

  34. Patz M, Pentok B, Cremer K, Linnartz S, Lilienweiss E, Kleinert F, et al. ROR-1 Is a highly discriminative marker in flow cytometric minimal residual disease (MRD) detection in chronic lymphocytic leukemia (CLL). Blood. 2016;128:3197.

    Google Scholar 

  35. Rawstron AC, Cohen D, De Tute RM, McParland L, Collett L, Phillips D, et al. The level of residual CLL objectively predicts the outcome of patients following FCR-based therapy with sequential benefits per log depletion and improved post-treatment monitoring. Blood. 2015;126:1717.

    Google Scholar 

  36. Kwok M, Rawstron AC, Varghese A, Evans PAS, O’Connor SJM, Doughty C, et al. Minimal residual disease is an independent predictor for 10-year survival in CLL. Blood. 2016;128:2770–3.

    Article  PubMed  CAS  Google Scholar 

  37. Carlson CS, Emerson RO, Sherwood AM, Desmarais C, Chung M-W, Parsons JM, et al. Using synthetic templates to design an unbiased multiplex PCR assay. Nat Commun. 2013;4:2680.

    Article  PubMed  CAS  Google Scholar 

  38. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446–56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Hillmen P, Skotnicki AB, Robak T, Jaksic B, Dmoszynska A, Wu J, et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol J Am Soc Clin Oncol. 2007;25:5616–23.

    Article  CAS  Google Scholar 

  40. O’Brien SM, Kantarjian HM, Cortes J, Beran M, Koller CA, Giles FJ, et al. Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia. J Clin Oncol J Am Soc Clin Oncol. 2001;19:1414–20.

    Article  Google Scholar 

  41. Robak T, Błoński JZ, Kasznicki M, Góra-Tybor J, Dwilewicz-Trojaczek J, Stella-Hołowiecka B, et al. Cladribine combined with cyclophosphamide is highly effective in the treatment of chronic lymphocytic leukemia. Hematol J J Eur Haematol Assoc EHA. 2002;3:244–50.

    CAS  Google Scholar 

  42. Kay NE, Geyer SM, Call TG, Shanafelt TD, Zent CS, Jelinek DF, et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood. 2007;109:405–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Wierda W, O’Brien S, Wen S, Faderl S, Garcia-Manero G, Thomas D, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol J Am Soc Clin Oncol. 2005;23:4070–8.

    Article  CAS  Google Scholar 

  44. Hillmen P, Cohen DR, Cocks K, Pettitt A, Sayala HA, Rawstron AC, et al. A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia. Br J Haematol. 2011;152:570–8.

    Article  PubMed  CAS  Google Scholar 

  45. Tam CS, O’Brien S, Wierda W, Kantarjian H, Wen S, Do K-A, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112:975–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Ritgen M, Böttcher S, Stilgenbauer S, Bunjes D, Schubert J, Cohen S, et al. Quantitative MRD monitoring identifies distinct GVL response patterns after allogeneic stem cell transplantation for chronic lymphocytic leukemia: results from the GCLLSG CLL3X trial. Leukemia. 2008;22:1377–86.

    Article  PubMed  CAS  Google Scholar 

  47. Caballero D, García-Marco JA, Martino R, Mateos V, Ribera JM, Sarrá J, et al. Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-). Clin Cancer Res J Am Assoc Cancer Res. 2005;11:7757–63.

    Article  CAS  Google Scholar 

  48. Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370:1101–10.

    Article  PubMed  CAS  Google Scholar 

  49. Hillmen P, Gribben JG, Follows GA, Milligan D, Sayala HA, Moreton P, et al. Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: final analysis of an open-label phase II study. J Clin Oncol J Am Soc Clin Oncol. 2014;32:1236–41.

    Article  CAS  Google Scholar 

  50. Thompson PA, Wierda WG. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL. Blood. 2016;127:279–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Böttcher S, Hallek M, Ritgen M, Kneba M. The role of minimal residual disease measurements in the therapy for CLL: is it ready for prime time? Hematol Oncol Clin North Am. 2013;27:267–88.

    Article  PubMed  Google Scholar 

  52. Ghia P. A look into the future: can minimal residual disease guide therapy and predict prognosis in chronic lymphocytic leukemia? Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2012;2012:97–104.

    Google Scholar 

  53. Kovacs G, Robrecht S, Fink AM, Bahlo J, Cramer P, von Tresckow J, et al. Minimal residual disease assessment improves prediction of outcome in patients with chronic lymphocytic leukemia (CLL) who achieve partial response: comprehensive analysis of two phase III studies of the German CLL Study Group. J Clin Oncol J Am Soc Clin Oncol. 2016;34:3758–65. https://doi.org/10.1200/JCO.2016.67.1305

    Article  CAS  Google Scholar 

  54. Rawstron AC, Howard D, McParland L, de Tute RM, Collett L, Phillips D, et al. Compartment effect on the prognostic significance of MRD detection in CLL: impact of treatment type and duration of follow-up. Blood. 2016;128:3226.

    Google Scholar 

  55. Varghese AM, Howard DR, Pocock C, Rawstron AC, Follows G, McCarthy H, et al. Eradication of minimal residual disease improves overall and progression-free survival in patients with chronic lymphocytic leukaemia, evidence from NCRN CLL207: a phase II trial assessing alemtuzumab consolidation. Br J Haematol. 2017;176:573–82.

    Article  PubMed  CAS  Google Scholar 

  56. Farooqui MZH, Valdez J, Martyr S, Aue G, Saba N, Niemann CU, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Lancet Oncol. 2015;16:169–76.

    Article  PubMed  CAS  Google Scholar 

  57. Burger JA, Keating MJ, Wierda WG, Hartmann E, Hoellenriegel J, Rosin NY, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2014;15:1090–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, Wagner-Johnston ND, et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014;123:3390–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370:997–1007.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. O’Brien SM, Furman RR, Coutre SE, Flinn IW, Burger J, Blum K, et al. Five-year experience with single-agent ibrutinib in patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia/small lymphocytic leukemia. Blood. 2016;128:233.

    Google Scholar 

  62. Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374:311–22.

    Article  PubMed  CAS  Google Scholar 

  63. Seymour JF, Ma S, Brander DM, Choi MY, Barrientos J, Davids MS, et al. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study. Lancet Oncol. 2017;18:230–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Chanan-Khan A, Cramer P, Demirkan F, Fraser G, Silva RS, Grosicki S, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2016;17:200–11.

    Article  PubMed  CAS  Google Scholar 

  65. Rawstron A, Munir T, Munoz-Vicente S, Brock K, Yates F, Bishop R, et al. Adding obinutuzumab to ibrutinib enhances depletion of Cll cells in peripheral blood and bone marrow after 1 & 6 months combined therapy initial results from the bloodwise tap iciclle extension study. Haematologica. 2017;102:69–69.

    Article  CAS  Google Scholar 

  66. Fink AM, Bahlo J, Robrecht S, Al-Sawaf O, Aldaoud A, Hebart H, et al. Lenalidomide maintenance after first-line therapy for high-risk chronic lymphocytic leukaemia (CLLM1): final results from a randomised, double-blind, phase 3 study. Lancet Haematol. 2017;4:e475–e486.

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was in part supported by Associazione Italiana contro il Cancro (AIRC)—Investigator grants #20246 and Special Program Molecular Clinical Oncology AIRC 5 per mille #9965 (to PG).

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  1. Università Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele, Milano, Italy

    Paolo Ghia

  2. Haematological Malignancy Diagnostic Service (HMDS), Leeds Teaching Hospitals NHS Trust, Leeds and Department of Health Sciences, University of York, York, UK

    Andy Rawstron

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Ghia, P., Rawstron, A. Minimal residual disease analysis in chronic lymphocytic leukemia: a way for achieving more personalized treatments. Leukemia 32, 1307–1316 (2018). https://doi.org/10.1038/s41375-018-0109-x

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