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Flow Cytometric Techniques in the Diagnosis and Monitoring of Acute Leukaemias

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Pathogenesis and Treatment of Leukemia

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Abstract

Flow cytometry has revolutionized the way acute leukaemias are diagnosed and monitored. This technique has enabled accurate diagnosis and classification of acute leukaemias. With more accurate methodology, flow cytometry allows detailed monitoring of acute leukaemias which has been shown to affect prognosis of the disease. In this chapter, we will discuss flow cytometry in the diagnosis of acute leukaemias touching on the technical aspects. We will then explore monitoring of acute leukaemias, especially in regard to minimal residual disease in acute lymphoblastic leukaemia and acute myeloid leukaemia.

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References

  1. Wood BL. Myeloid malignancies: myelodysplastic syndromes, Myeloproliferative disorders, and acute myeloid leukemia. Clin Lab Med. 2007;27(3):551–75.

    PubMed  Google Scholar 

  2. Porwit A, Béné M-C. Flow cytometry of normal blood, bone marrow and lymphatic tissue. In: Porwit A, Béné MC, editors. Multiparameter flow cytometry in the diagnosis of hematologic malignancies. Cambridge: Cambridge University Press; 2018. p. 36–60.

    Google Scholar 

  3. Foon KA, Todd RF 3rd. Immunologic classification of leukemia and lymphoma. Blood. 1986;68(1):1–31.

    CAS  PubMed  Google Scholar 

  4. Craig FE, Foon KA. Flow cytometric immunophenotyping for hematologic neoplasms. Blood. 2008;111(8):3941–67.

    CAS  PubMed  Google Scholar 

  5. Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9(10):1783–6.

    CAS  PubMed  Google Scholar 

  6. Jennings CD, Foon KA. Recent advances in flow cytometry: application to the diagnosis of hematologic malignancy. Blood. 1997;90(8):2863–92.

    CAS  PubMed  Google Scholar 

  7. van Dongen JJM, Lhermitte L, Böttcher S, Almeida J, van der Velden VHJ, Flores-Montero J, et al. EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia. 2012;26(9):1908–75.

    PubMed  PubMed Central  Google Scholar 

  8. Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10(2):147–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Niehues T, Kapaun P, Harms DO, Burdach S, Kramm C, Körholz D, et al. A classification based on T cell selection-related phenotypes identifies a subgroup of childhood T-ALL with favorable outcome in the COALL studies. Leukemia. 1999;13(4):614–7.

    CAS  PubMed  Google Scholar 

  10. Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, et al. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009;114(25):5136–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. DiGiuseppe JA. Acute lymphoblastic leukemia: diagnosis and detection of minimal residual disease following therapy. Clin Lab Med. 2007;27(3):533–49.

    PubMed  Google Scholar 

  12. Swerdlow S, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer; 2017.

    Google Scholar 

  13. Lúcio P, Parreira A, van den Beemd MW, van Lochem EG, van Wering ER, Baars E, et al. Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. Leukemia. 1999;13(3):419–27.

    PubMed  Google Scholar 

  14. Wood BL. Ten-color immunophenotyping of hematopoietic cells. Curr Protoc Cytom. 2005;33(1):6.21.1.

    Google Scholar 

  15. Orfao A, Matarraz S, Pérez-Andrés M, Almeida J, Teodosio C, Berkowska MA, et al. Immunophenotypic dissection of normal hematopoiesis. J Immunol Methods. 2019;475:112684.

    CAS  PubMed  Google Scholar 

  16. Schuurhuis GJ, Heuser M, Freeman S, Béné M-C, Buccisano F, Cloos J, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD working party. Blood. 2018;131(12):1275–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Brüggemann M, Kotrova M. Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation. Blood Adv. 2017;1(25):2456–66.

    PubMed  PubMed Central  Google Scholar 

  18. Flores-Montero J, Sanoja-Flores L, Paiva B, Puig N, García-Sánchez O, Böttcher S, et al. Next generation flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia. 2017;31(10):2094–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Theunissen P, Mejstrikova E, Sedek L, van der Sluijs-Gelling AJ, Gaipa G, Bartels M, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood. 2017;129(3):347–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Donnenberg AD, Donnenberg VS. Rare-event analysis in flow cytometry. Clin Lab Med. 2007;27(3):627–52.

    PubMed  Google Scholar 

  21. Tembhare PR, Ghogale S, Ghatwai N, Badrinath Y, Kunder N, Patkar NV, et al. Evaluation of new markers for minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia: CD73 and CD86 are the most relevant new markers to increase the efficacy of MRD 2016; 00B: 000–000. Cytometry B Clin Cytom. 2018;94(1):100–11.

    CAS  PubMed  Google Scholar 

  22. Sędek Ł, Theunissen P, Sobral da Costa E, van der Sluijs-Gelling A, Mejstrikova E, Gaipa G, et al. Differential expression of CD73, CD86 and CD304 in normal vs. leukemic B-cell precursors and their utility as stable minimal residual disease markers in childhood B-cell precursor acute lymphoblastic leukemia. J Immunol Methods. 2019;475:112429.

    PubMed  Google Scholar 

  23. Coustan-Smith E, Song G, Clark C, Key L, Liu P, Mehrpooya M, et al. New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2011;117(23):6267–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Coustan-Smith E, Sancho J, Hancock ML, Razzouk BI, Ribeiro RC, Rivera GK, et al. Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia. Blood. 2002;100(7):2399–402.

    CAS  PubMed  Google Scholar 

  25. van der Velden VH, Jacobs DC, Wijkhuijs AJ, Comans-Bitter WM, Willemse MJ, Hählen K, et al. Minimal residual disease levels in bone marrow and peripheral blood are comparable in children with T cell acute lymphoblastic leukemia (ALL), but not in precursor-B-ALL. Leukemia. 2002;16(8):1432–6.

    PubMed  Google Scholar 

  26. Cherian S, Stetler-Stevenson M. Flow cytometric monitoring for residual disease in B lymphoblastic leukemia post T cell engaging targeted therapies. Curr Protoc Cytom. 2018;86(1):e44.

    PubMed  PubMed Central  Google Scholar 

  27. Zeijlemaker W, Gratama JW, Schuurhuis GJ. Tumor heterogeneity makes AML a “moving target” for detection of residual disease. Cytometry B Clin Cytom. 2014;86(1):3–14.

    CAS  PubMed  Google Scholar 

  28. Hasserjian RP, Steensma DP, Graubert TA, Ebert BL. Clonal hematopoiesis and measurable residual disease assessment in acute myeloid leukemia. Blood. 2020;135(20):1729–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Jaso JM, Wang SA, Jorgensen JL, Lin P. Multi-color flow cytometric immunophenotyping for detection of minimal residual disease in AML: past, present and future. Bone Marrow Transplant. 2014;49(9):1129–38.

    CAS  PubMed  Google Scholar 

  30. Zeijlemaker W, Kelder A, Oussoren-Brockhoff YJM, Scholten WJ, Snel AN, Veldhuizen D, et al. A simple one-tube assay for immunophenotypical quantification of leukemic stem cells in acute myeloid leukemia. Leukemia. 2015;30:439.

    PubMed  Google Scholar 

  31. Grimwade D, Freeman SD. Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”? Blood. 2014;124(23):3345–55.

    CAS  PubMed  Google Scholar 

  32. Wood BL. Acute myeloid leukemia minimal residual disease detection: the difference from Normal approach. Curr Protoc Cytom. 2020;93(1):e73.

    CAS  PubMed  Google Scholar 

  33. Al-Mawali A, Gillis D, Lewis I. The use of receiver operating characteristic analysis for detection of minimal residual disease using five-color multiparameter flow cytometry in acute myeloid leukemia identifies patients with high risk of relapse. Cytometry B Clin Cytom. 2009;76B(2):91–101.

    Google Scholar 

  34. Maurillo L, Buccisano F, Del Principe MI, Del Poeta G, Spagnoli A, Panetta P, et al. Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(30):4944–51.

    Google Scholar 

  35. Voskova D, Schnittger S, Schoch C, Haferlach T, Kern W. Use of five-color staining improves the sensitivity of multiparameter flow cytomeric assessment of minimal residual disease in patients with acute myeloid leukemia. Leuk Lymphoma. 2007;48(1):80–8.

    CAS  PubMed  Google Scholar 

  36. Feller N, van der Velden VHJ, Brooimans RA, Boeckx N, Preijers F, Kelder A, et al. Defining consensus leukemia-associated immunophenotypes for detection of minimal residual disease in acute myeloid leukemia in a multicenter setting. Blood Cancer J. 2013;3(8):e129.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Giebel S, Stella-Holowiecka B, Krawczyk-Kulis M, Gökbuget N, Hoelzer D, Doubek M, et al. Status of minimal residual disease determines outcome of autologous hematopoietic SCT in adult ALL. Bone Marrow Transplant. 2009;45(6):1095–101.

    PubMed  Google Scholar 

  38. Holowiecki J, Krawczyk-Kulis M, Giebel S, Jagoda K, Stella-Holowiecka B, Piatkowska-Jakubas B, et al. Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD study. Br J Haematol. 2008;142(2):227–37.

    PubMed  Google Scholar 

  39. Weng XQ, Shen Y, Sheng Y, Chen B, Wang JH, Li JM, et al. Prognostic significance of monitoring leukemia-associated immunophenotypes by eight-color flow cytometry in adult B-acute lymphoblastic leukemia. Blood Cancer J. 2013;3(8):e133.

    PubMed  PubMed Central  Google Scholar 

  40. Short NJ, Jabbour E, Albitar M, de Lima M, Gore L, Jorgensen J, et al. Recommendations for the assessment and management of measurable residual disease in adults with acute lymphoblastic leukemia: a consensus of north American experts. Am J Hematol. 2019;94(2):257–65.

    PubMed  Google Scholar 

  41. Brown PA, Shah B, Advani A. Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(9):1079–109. https://doi.org/10.6004/jnccn.2021.0042.

  42. Hoelzer D, Bassan R, Dombret H, Fielding A, Ribera JM, Buske C. Acute lymphoblastic leukaemia in adult patients: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v69–82.

    CAS  PubMed  Google Scholar 

  43. Giebel S, Marks DI, Boissel N, Baron F, Chiaretti S, Ciceri F, et al. Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the acute leukemia working Party of the European Society for blood and marrow transplantation (EBMT). Bone Marrow Transplant. 2019;54(6):798–809.

    PubMed  Google Scholar 

  44. Coustan-Smith E, Behm FG, Sanchez J, Boyett JM, Hancock ML, Raimondi SC, et al. Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia. Lancet. 1998;351(9102):550–4.

    CAS  PubMed  Google Scholar 

  45. Coustan-Smith E, Gajjar A, Hijiya N, Razzouk BI, Ribeiro RC, Rivera GK, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse. Leukemia. 2004;18(3):499–504.

    CAS  PubMed  Google Scholar 

  46. Coustan-Smith E, Sancho J, Behm FG, Hancock ML, Razzouk BI, Ribeiro RC, et al. Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia. Blood. 2002;100(1):52–8.

    CAS  PubMed  Google Scholar 

  47. Basso G, Veltroni M, Valsecchi MG, Dworzak MN, Ratei R, Silvestri D, et al. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol. 2009;27(31):5168–74.

    PubMed  Google Scholar 

  48. Vidriales MB, Pérez JJ, López-Berges MC, Gutiérrez N, Ciudad J, Lucio P, et al. Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value. Blood. 2003;101(12):4695–700.

    CAS  PubMed  Google Scholar 

  49. Ravandi F, Jorgensen JL, O’Brien SM, Jabbour E, Thomas DA, Borthakur G, et al. Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia. Br J Haematol. 2016;172(3):392–400.

    CAS  PubMed  Google Scholar 

  50. Gökbuget N, Dombret H, Giebel S, Bruggemann M, Doubek M, Foà R, et al. Minimal residual disease level predicts outcome in adults with Ph-negative B-precursor acute lymphoblastic leukemia. Hematology. 2019;24(1):337–48.

    PubMed  Google Scholar 

  51. Berry DA, Zhou S, Higley H, Mukundan L, Fu S, Reaman GH, et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis. JAMA Oncol. 2017;3(7):e170580.

    PubMed  PubMed Central  Google Scholar 

  52. Bassan R, Brüggemann M, Radcliffe HS, Hartfield E, Kreuzbauer G, Wetten S. A systematic literature review and meta-analysis of minimal residual disease as a prognostic indicator in adult B-cell acute lymphoblastic leukemia. Haematologica. 2019;104(10):2028–39.

    PubMed  PubMed Central  Google Scholar 

  53. Brüggemann M, Raff T, Flohr T, Gökbuget N, Nakao M, Droese J, et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006;107(3):1116–23.

    PubMed  Google Scholar 

  54. Dhédin N, Huynh A, Maury S, Tabrizi R, Beldjord K, Asnafi V, et al. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia. Blood. 2015;125(16):2486–96; quiz 586.

    PubMed  Google Scholar 

  55. Gökbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R, et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120(9):1868–76.

    PubMed  Google Scholar 

  56. Raff T, Gökbuget N, Lüschen S, Reutzel R, Ritgen M, Irmer S, et al. Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. Blood. 2007;109(3):910–5.

    CAS  PubMed  Google Scholar 

  57. Giebel S, Labopin M, Socié G, Beelen D, Browne P, Volin L, et al. Improving results of allogeneic hematopoietic cell transplantation for adults with acute lymphoblastic leukemia in first complete remission: an analysis from the acute leukemia working Party of the European Society for blood and marrow transplantation. Haematologica. 2017;102(1):139–49.

    PubMed  PubMed Central  Google Scholar 

  58. Bar M, Wood BL, Radich JP, Doney KC, Woolfrey AE, Delaney C, et al. Impact of minimal residual disease, detected by flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia. Leuk Res Treatment. 2014;2014:421723.

    PubMed  PubMed Central  Google Scholar 

  59. Brammer JE, Saliba RM, Jorgensen JL, Ledesma C, Gaballa S, Poon M, et al. Multi-center analysis of the effect of T-cell acute lymphoblastic leukemia subtype and minimal residual disease on allogeneic stem cell transplantation outcomes. Bone Marrow Transplant. 2017;52(1):20–7.

    CAS  PubMed  Google Scholar 

  60. Ribera JM, Oriol A, Morgades M, Montesinos P, Sarrà J, González-Campos J, et al. Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol. 2014;32(15):1595–604.

    CAS  PubMed  Google Scholar 

  61. Pemmaraju N, Kantarjian H, Jorgensen JL, Jabbour E, Jain N, Thomas D, et al. Significance of recurrence of minimal residual disease detected by multi-parameter flow cytometry in patients with acute lymphoblastic leukemia in morphological remission. Am J Hematol. 2017;92(3):279–85.

    PubMed  PubMed Central  Google Scholar 

  62. Zugmaier G, Gökbuget N, Klinger M, Viardot A, Stelljes M, Neumann S, et al. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood. 2015;126(24):2578–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Jabbour E, Gökbuget N, Advani A, Stelljes M, Stock W, Liedtke M, et al. Impact of minimal residual disease status in patients with relapsed/refractory acute lymphoblastic leukemia treated with inotuzumab ozogamicin in the phase III INO-VATE trial. Leuk Res. 2020;88:106283.

    CAS  PubMed  Google Scholar 

  64. Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131(14):1522–31.

    PubMed  PubMed Central  Google Scholar 

  65. Hilal T, Prasad V. Eliminating MRD–FDA approval of blinatumomab for B-ALL in complete remission. Nat Rev Clin Oncol. 2018;15(12):727–8.

    CAS  PubMed  Google Scholar 

  66. Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378(5):449–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Ravandi F, Jorgensen J, Borthakur G, Jabbour E, Kadia T, Pierce S, et al. Persistence of minimal residual disease assessed by multiparameter flow cytometry is highly prognostic in younger patients with acute myeloid leukemia. Cancer. 2017;123(3):426–35.

    CAS  PubMed  Google Scholar 

  68. Terwijn M, van Putten WLJ, Kelder A, van der Velden VHJ, Brooimans RA, Pabst T, et al. High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. J Clin Oncol. 2013;31(31):3889–97.

    PubMed  Google Scholar 

  69. Freeman SD, Virgo P, Couzens S, Grimwade D, Russell N, Hills RK, et al. Prognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia. J Clin Oncol. 2013;31(32):4123–31.

    PubMed  Google Scholar 

  70. Vidriales M-B, Pérez-López E, Pegenaute C, Castellanos M, Pérez J-J, Chandía M, et al. Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia. Leuk Res. 2016;40:1–9.

    PubMed  Google Scholar 

  71. Paiva B, Vidriales M-B, Sempere A, Tarín F, Colado E, Benavente C, et al. Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia. Leukemia. 2021;35(8):2358–70.

    CAS  PubMed  Google Scholar 

  72. Langebrake C, Creutzig U, Dworzak M, Hrusak O, Mejstrikova E, Griesinger F, et al. Residual disease monitoring in childhood acute myeloid leukemia by multiparameter flow cytometry: the MRD-AML-BFM study group. J Clin Oncol. 2006;24(22):3686–92.

    PubMed  Google Scholar 

  73. van der Velden VHJ, van der Sluijs-Geling A, Gibson BES, te Marvelde JG, Hoogeveen PG, Hop WCJ, et al. Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol. Leukemia. 2010;24(9):1599–606.

    PubMed  Google Scholar 

  74. Inaba H, Coustan-Smith E, Cao X, Pounds SB, Shurtleff SA, Wang KY, et al. Comparative analysis of different approaches to measure treatment response in acute myeloid leukemia. J Clin Oncol. 2012;30(29):3625–32.

    PubMed  PubMed Central  Google Scholar 

  75. Loken MR, Alonzo TA, Pardo L, Gerbing RB, Raimondi SC, Hirsch BA, et al. Residual disease detected by multidimensional flow cytometry signifies high relapse risk in patients with de novo acute myeloid leukemia: a report from Children’s Oncology Group. Blood. 2012;120(8):1581–8.

    PubMed  PubMed Central  Google Scholar 

  76. Buldini B, Rizzati F, Masetti R, Fagioli F, Menna G, Micalizzi C, et al. Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol. Br J Haematol. 2017;177(1):116–26.

    PubMed  Google Scholar 

  77. Tierens A, Bjørklund E, Siitonen S, Marquart HV, Wulff-Juergensen G, Pelliniemi T-T, et al. Residual disease detected by flow cytometry is an independent predictor of survival in childhood acute myeloid leukaemia; results of the NOPHO-AML 2004 study. Br J Haematol. 2016;174(4):600–9.

    PubMed  Google Scholar 

  78. Venditti A, Buccisano F, Del Poeta G, Maurillo L, Tamburini A, Cox C, et al. Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood. 2000;96(12):3948–52.

    CAS  PubMed  Google Scholar 

  79. Walter RB, Gooley TA, Wood BL, Milano F, Fang M, Sorror ML, et al. Impact of pretransplantation minimal residual disease, as detected by multiparametric flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute myeloid leukemia. J Clin Oncol. 2011;29(9):1190–7.

    PubMed  PubMed Central  Google Scholar 

  80. Walter RB, Buckley SA, Pagel JM, Wood BL, Storer BE, Sandmaier BM, et al. Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission. Blood. 2013;122(10):1813–21.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Walter RB, Gyurkocza B, Storer BE, Godwin CD, Pagel JM, Buckley SA, et al. Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia. 2015;29(1):137–44.

    CAS  PubMed  Google Scholar 

  82. Araki D, Wood BL, Othus M, Radich JP, Halpern AB, Zhou Y, et al. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: time to move toward a minimal residual disease-based definition of complete remission? J Clin Oncol. 2016;34(4):329–36.

    PubMed  Google Scholar 

  83. Burchert A, Bug G, Fritz LV, Finke J, Stelljes M, Röllig C, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020;38(26):2993–3002.

    PubMed  Google Scholar 

  84. Larson RA, Mandrekar SJ, Huebner LJ, Sanford BL, Laumann K, Geyer S, et al. Midostaurin reduces relapse in FLT3-mutant acute myeloid leukemia: the Alliance CALGB 10603/RATIFY trial. Leukemia. 2021;35(9):2539–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Platzbecker U, Wermke M, Radke J, Oelschlaegel U, Seltmann F, Kiani A, et al. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia. 2012;26(3):381–9.

    CAS  PubMed  Google Scholar 

  86. Maintenance therapy improves AML outcomes regardless of MRD status or consolidation cycles. Oncologist. 2021;26(Suppl 1):S6–7.

    Google Scholar 

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Authors and Affiliations

  1. Department of Haematology-Oncology, National University Cancer Institute Singapore, National University Health System Singapore, Singapore, Singapore

    Melissa G. Ooi, Pak Ling Lui & Shir Ying Lee

  2. Department of Medicine, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore

    Melissa G. Ooi & Shir Ying Lee

  3. Department of Laboratory Medicine, National University Health System Singapore, Singapore, Singapore

    Pak Ling Lui, Te Chih Liu & Shir Ying Lee

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  1. Melissa G. Ooi
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Correspondence to Melissa G. Ooi .

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  1. Department of Medicine, Queen Mary Hospital, Hongkong, Hong Kong

    Harinder Gill

  2. Department of Medicine, Queen Mary Hospital, Hongkong, Hong Kong

    Yok-Lam Kwong

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Ooi, M.G., Lui, P.L., Liu, T.C., Lee, S.Y. (2023). Flow Cytometric Techniques in the Diagnosis and Monitoring of Acute Leukaemias. In: Gill, H., Kwong, YL. (eds) Pathogenesis and Treatment of Leukemia. Springer, Singapore. https://doi.org/10.1007/978-981-99-3810-0_4

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