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CC BY 4.0 · Indian J Med Paediatr Oncol 2023; 44(06): 566-577
DOI: 10.1055/s-0043-1762921
Review Article

Molecular MRD Assessment in Acute Myeloid Leukemias

Shivangi Harankhedkar 
1   Haematopathology Laboratory, ACTREC, Tata Memorial Centre, Navi Mumbai, Maharashtra, India
2   Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
,
Nikhil Patkar 
1   Haematopathology Laboratory, ACTREC, Tata Memorial Centre, Navi Mumbai, Maharashtra, India
2   Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
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Abstract

Detection of measurable residual disease (MRD) is of significant value in the management of acute myeloid leukemia (AML) patients. Along with multicolor flowcytometry (MFC), molecular techniques form an integral tool in AML MRD detection. Multiple studies have reiterated the role of molecular MRD evaluation in AML at defined timepoints during the course of therapy, helping in risk stratification, prediction of relapse, and as guide for pre-emptive therapy. The latest World Health Organization (WHO) classification (WHO-HEME5) has refined the classification of AML bringing forth newer entities defined by molecular abnormalities, especially fusions. AML is a clonally heterogeneous disease characterized by a spectrum of multiple molecular abnormalities including gene mutations and fusions. Accordingly, the molecular methods employed are also diverse and need robust technical standardization in clinical laboratories. Real-time quantitative polymerase chain reaction (PCR), digital PCR, and next-generation sequencing (NGS) are the major molecular platforms for AML MRD. The European LeukemiaNet (ELN) MRD Working Party consensus document recently updated in 2021 for the first time has reflected on the technical recommendations for NGS MRD in AML and stressed the value of an integrated approach. It is, therefore, desirable for physicians, scientists, and pathologists alike to thoroughly understand these molecular methods for appropriate utilization and interpretation. In this article, we discuss the various facets of molecular methods for MRD detection in AML including technical requirements, advantages, drawbacks, and applications.

Keywords

molecular MRD - error corrected next-generation sequencing - measurable residual disease


Publication History

Article published online:
17 April 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Kantarjian H, Kadia T, DiNardo C. et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J 2021; 11 (02) 41
    CrossrefPubMedGoogle Scholar
  • 2 Patkar N, Kakirde C, Bhanshe P. et al. Utility of immunophenotypic measurable residual disease in adult acute myeloid leukemiareal-world context. Front Oncol 2019; 9: 450
    CrossrefPubMedGoogle Scholar
  • 3 Heuser M, Freeman SD, Ossenkoppele GJ. et al. 2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party. Blood 2021; 138 (26) 2753-2767
    CrossrefPubMedGoogle Scholar
  • 4 Khoury JD, Solary E, Abla O. et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 2022; 36 (07) 1703-1719
    CrossrefPubMedGoogle Scholar
  • 5 Rautenberg C, Lauseker M, Kaivers J. et al. Prognostic impact of pretransplant measurable residual disease assessed by peripheral blood WT1-mRNA expression in patients with AML and MDS. Eur J Haematol 2021; 107 (02) 283-292
    CrossrefPubMedGoogle Scholar
  • 6 Weisser M, Kern W, Rauhut S. et al. Prognostic impact of RT-PCR-based quantification of WT1 gene expression during MRD monitoring of acute myeloid leukemia. Leukemia 2005; 19 (08) 1416-1423
    CrossrefPubMedGoogle Scholar
  • 7 Najima Y, Ohashi K, Kawamura M. et al. Molecular monitoring of BAALC expression in patients with CD34-positive acute leukemia. Int J Hematol 2010; 91 (04) 636-645
    CrossrefPubMedGoogle Scholar
  • 8 Weber S, Alpermann T, Dicker F. et al. BAALC expression: a suitable marker for prognostic risk stratification and detection of residual disease in cytogenetically normal acute myeloid leukemia. Blood Cancer J 2014; 4 (01) e173
    CrossrefPubMedGoogle Scholar
  • 9 Lazzarotto D, Candoni A. The role of Wilms' Tumor Gene (WT1) expression as a marker of minimal residual disease in acute myeloid leukemia. J Clin Med 2022; 11 (12) 3306
    CrossrefPubMedGoogle Scholar
  • 10 Qin Y, Zhu H, Jiang B. et al. Expression patterns of WT1 and PRAME in acute myeloid leukemia patients and their usefulness for monitoring minimal residual disease. Leuk Res 2009; 33 (03) 384-390
    CrossrefPubMedGoogle Scholar
  • 11 Jentzsch M, Bill M, Grimm J. et al. Prognostic impact of blood MN1 copy numbers before allogeneic stem cell transplantation in patients with acute myeloid leukemia. HemaSphere 2019; 3 (01) e167
    CrossrefPubMedGoogle Scholar
  • 12 Tsirigotis P, Byrne M, Schmid C. et al. Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT. Bone Marrow Transplant 2016; 51 (11) 1431-1438
    CrossrefPubMedGoogle Scholar
  • 13 Zhong L, Chen J, Huang X, Li Y, Jiang T. Monitoring immunoglobulin heavy chain and T-cell receptor gene rearrangement in cfDNA as minimal residual disease detection for patients with acute myeloid leukemia. Oncol Lett 2018; 16 (02) 2279-2288
    PubMedGoogle Scholar
  • 14 Panuzzo C, Jovanovski A, Ali MS, Cilloni D, Pergolizzi B. Revealing the mysteries of acute myeloid leukemia: from quantitative PCR through next-generation sequencing and systemic metabolomic profiling. J Clin Med 2022; 11 (03) 483
    CrossrefPubMedGoogle Scholar
  • 15 Ediriwickrema A, Aleshin A, Reiter JG. et al. Single-cell mutational profiling enhances the clinical evaluation of AML MRD. [published correction appears in Blood Adv. 2020 Apr 14;4(7):1218] Blood Adv 2020; 4 (05) 943-952
    CrossrefPubMedGoogle Scholar
  • 16 Thol F, Gabdoulline R, Liebich A. et al. Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML. Blood 2018; 132 (16) 1703-1713
    CrossrefPubMedGoogle Scholar
  • 17 Skou AS, Juul-Dam KL, Ommen HB, Hasle H. Peripheral blood molecular measurable residual disease is sufficient to identify patients with acute myeloid leukaemia with imminent clinical relapse. Br J Haematol 2021; 195 (03) 310-327
    CrossrefPubMedGoogle Scholar
  • 18 Dvorakova D, Racil Z, Jeziskova I. et al. Monitoring of minimal residual disease in acute myeloid leukemia with frequent and rare patient-specific NPM1 mutations. Am J Hematol 2010; 85 (12) 926-929
    CrossrefPubMedGoogle Scholar
  • 19 Ivey A, Hills RK, Simpson MA. et al; UK National Cancer Research Institute AML Working Group. Assessment of minimal residual disease in standard-risk AML. N Engl J Med 2016; 374 (05) 422-433
    CrossrefPubMedGoogle Scholar
  • 20 Balsat M, Renneville A, Thomas X. et al. Postinduction minimal residual disease predicts outcome and benefit from allogeneic stem cell transplantation in acute myeloid leukemia with NPM1 mutation: a study by the Acute Leukemia French Association Group. J Clin Oncol 2017; 35 (02) 185-193
    CrossrefPubMedGoogle Scholar
  • 21 Chou WC, Tang JL, Wu SJ. et al. Clinical implications of minimal residual disease monitoring by quantitative polymerase chain reaction in acute myeloid leukemia patients bearing nucleophosmin (NPM1) mutations. Leukemia 2007; 21 (05) 998-1004
    CrossrefPubMedGoogle Scholar
  • 22 Abdelhamid E, Besbes S, Renneville A. et al. Minimal residual disease assessment of IDH1/2 mutations in acute myeloid leukemia by LNA-RQ-PCR. Tunis Med 2016; 94 (03) 190-197
    PubMedGoogle Scholar
  • 23 Petrova L, Vrbacky F, Lanska M, Zavrelova A, Zak P, Hrochova K. IDH1 and IDH2 mutations in patients with acute myeloid leukemia: Suitable targets for minimal residual disease monitoring?. [published correction appears in Clin Biochem. 2019 Jan;63:161] Clin Biochem 2018; 61: 34-39
    CrossrefPubMedGoogle Scholar
  • 24 Gaidzik VI, Weber D, Paschka P. et al; German-Austrian Acute Myeloid Leukemia Study Group (AMLSG). DNMT3A mutant transcript levels persist in remission and do not predict outcome in patients with acute myeloid leukemia. Leukemia 2018; 32 (01) 30-37
    CrossrefPubMedGoogle Scholar
  • 25 Beillard E, Pallisgaard N, van der Velden VH. et al. 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 2003; 17 (12) 2474-2486
    CrossrefPubMedGoogle Scholar
  • 26 Gabert J, Beillard E, van der Velden VH. et al. 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 2003; 17 (12) 2318-2357
    CrossrefPubMedGoogle Scholar
  • 27 Viehmann S, Teigler-Schlegel A, Bruch J, Langebrake C, Reinhardt D, Harbott J. Monitoring of minimal residual disease (MRD) by real-time quantitative reverse transcription PCR (RQ-RT-PCR) in childhood acute myeloid leukemia with AML1/ETO rearrangement. Leukemia 2003; 17 (06) 1130-1136
    CrossrefPubMedGoogle Scholar
  • 28 Perea G, Lasa A, Aventín A. et al; Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)]. Leukemia 2006; 20 (01) 87-94
    CrossrefPubMedGoogle Scholar
  • 29 Corbacioglu A, Scholl C, Schlenk RF. et al. Prognostic impact of minimal residual disease in CBFB-MYH11-positive acute myeloid leukemia. J Clin Oncol 2010; 28 (23) 3724-3729
    CrossrefPubMedGoogle Scholar
  • 30 Yin JA, O'Brien MA, Hills RK, Daly SB, Wheatley K, Burnett AK. Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial. Blood 2012; 120 (14) 2826-2835
    CrossrefPubMedGoogle Scholar
  • 31 Zhu HH, Zhang XH, Qin YZ. et al. MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial. Blood 2013; 121 (20) 4056-4062
    CrossrefPubMedGoogle Scholar
  • 32 Jourdan E, Boissel N, Chevret S. et al; French AML Intergroup. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood 2013; 121 (12) 2213-2223
    CrossrefPubMedGoogle Scholar
  • 33 Wang Y, Wu DP, Liu QF. et al. In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification. Blood 2014; 124 (12) 1880-1886
    CrossrefPubMedGoogle Scholar
  • 34 Willekens C, Blanchet O, Renneville A. et al; French AML Intergroup. Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial. Haematologica 2016; 101 (03) 328-335
    CrossrefPubMedGoogle Scholar
  • 35 Grimwade D, Jovanovic JV, Hills RK. et al. Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol 2009; 27 (22) 3650-3658
    CrossrefPubMedGoogle Scholar
  • 36 Gorello P, Cazzaniga G, Alberti F. et al. Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations. Leukemia 2006; 20 (06) 1103-1108
    CrossrefPubMedGoogle Scholar
  • 37 Papadaki C, Dufour A, Seibl M. et al. Monitoring minimal residual disease in acute myeloid leukaemia with NPM1 mutations by quantitative PCR: clonal evolution is a limiting factor. Br J Haematol 2009; 144 (04) 517-523
    CrossrefPubMedGoogle Scholar
  • 38 Schnittger S, Kern W, Tschulik C. et al. Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML. Blood 2009; 114 (11) 2220-2231
    CrossrefPubMedGoogle Scholar
  • 39 Krönke J, Schlenk RF, Jensen KO. et al. Monitoring of minimal residual disease in NPM1-mutated acute myeloid leukemia: a study from the German-Austrian acute myeloid leukemia study group. J Clin Oncol 2011; 29 (19) 2709-2716
    CrossrefPubMedGoogle Scholar
  • 40 Shayegi N, Kramer M, Bornhäuser M. et al; Study Alliance Leukemia (SAL). The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML. Blood 2013; 122 (01) 83-92 DOI: 10.1182/blood-2012-10-461749.
    CrossrefPubMedGoogle Scholar
  • 41 Salipante SJ, Fromm JR, Shendure J, Wood BL, Wu D. Detection of minimal residual disease in NPM1-mutated acute myeloid leukemia by next-generation sequencing. Mod Pathol 2014; 27 (11) 1438-1446
    CrossrefPubMedGoogle Scholar
  • 42 Patkar N, Kodgule R, Kakirde C. et al. Clinical impact of measurable residual disease monitoring by ultradeep next generation sequencing in NPM1 mutated acute myeloid leukemia. Oncotarget 2018; 9 (93) 36613-36624
    CrossrefPubMedGoogle Scholar
  • 43 Tsai CH, Tang JL, Tien FM. et al. Clinical implications of sequential MRD monitoring by NGS at 2 time points after chemotherapy in patients with AML. Blood Adv 2021; 5 (10) 2456-2466
    CrossrefPubMedGoogle Scholar
  • 44 Abdelhamid E, Preudhomme C, Helevaut N. et al. Minimal residual disease monitoring based on FLT3 internal tandem duplication in adult acute myeloid leukemia. Leuk Res 2012; 36 (03) 316-323
    CrossrefPubMedGoogle Scholar
  • 45 Ravandi F, Walter RB, Freeman SD. Evaluating measurable residual disease in acute myeloid leukemia. Blood Adv 2018; 2 (11) 1356-1366
    CrossrefPubMedGoogle Scholar
  • 46 Huggett JF, Foy CA, Benes V. et al. The digital MIQE guidelines: minimum information for publication of quantitative digital PCR experiments. Clin Chem 2013; 59 (06) 892-902
    CrossrefPubMedGoogle Scholar
  • 47 Huggett JF. dMIQE Group. The digital MIQE guidelines update: minimum information for publication of quantitative digital PCR experiments for 2020. [published correction appears in Clin Chem. 2020 Nov 1;66(11):1464] Clin Chem 2020; 66 (08) 1012-1029
    CrossrefPubMedGoogle Scholar
  • 48 Mencia-Trinchant N, Hu Y, Alas MA. et al. Minimal residual disease monitoring of acute myeloid leukemia by massively multiplex digital PCR in patients with NPM1 mutations. J Mol Diagn 2017; 19 (04) 537-548
    CrossrefPubMedGoogle Scholar
  • 49 Ferret Y, Boissel N, Helevaut N. et al. Clinical relevance of IDH1/2 mutant allele burden during follow-up in acute myeloid leukemia. A study by the French ALFA group. Haematologica 2018; 103 (05) 822-829
    CrossrefPubMedGoogle Scholar
  • 50 Winters A, Goosman M, Stevens BM. et al. Tracking of AM associated mutations via droplet digital PCR is predictive of outcomes post-transplant. Blood 2018; 132: 2138
    CrossrefGoogle Scholar
  • 51 Brunetti C, Anelli L, Zagaria A. et al. Droplet digital PCR is a reliable tool for monitoring minimal residual disease in acute promyelocytic leukemia. J Mol Diagn 2017; 19 (03) 437-444
    CrossrefPubMedGoogle Scholar
  • 52 Brambati C, Galbiati S, Xue E. et al. Droplet digital polymerase chain reaction for DNMT3A and IDH1/2 mutations to improve early detection of acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation. Haematologica 2016; 101 (04) e157-e161
    CrossrefPubMedGoogle Scholar
  • 53 Bill M, Grimm J, Jentzsch M. et al. Digital droplet PCR-based absolute quantification of pre-transplant NPM1 mutation burden predicts relapse in acute myeloid leukemia patients. Ann Hematol 2018; 97 (10) 1757-1765
    CrossrefPubMedGoogle Scholar
  • 54 Grassi S, Guerrini F, Ciabatti E. et al. Digital droplet PCR is a specific and sensitive tool for detecting IDH2 mutations in acute myeloid leukemia patients. Cancers (Basel) 2020; 12 (07) 30
    CrossrefPubMedGoogle Scholar
  • 55 Klco JM, Miller CA, Griffith M. et al. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia. JAMA 2015; 314 (08) 811-822
    CrossrefPubMedGoogle Scholar
  • 56 Getta BM, Devlin SM, Levine RL. et al. Multicolor Flow Cytometry and Multigene Next-Generation Sequencing Are Complementary and Highly Predictive for Relapse in Acute Myeloid Leukemia after Allogeneic Transplantation. Biol Blood Marrow Transplant 2017; 23 (07) 1064-1071
    CrossrefPubMedGoogle Scholar
  • 57 Jongen-Lavrencic M, Grob T, Hanekamp D. et al. Molecular Minimal Residual Disease in Acute Myeloid Leukemia. N Engl J Med 2018; 378 (13) 1189-1199
    CrossrefPubMedGoogle Scholar
  • 58 Kim T, Moon JH, Ahn JS. et al. Next-generation sequencing-based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse. Blood 2018; 132 (15) 1604-1613
    CrossrefPubMedGoogle Scholar
  • 59 Morita K, Kantarjian HM, Wang F. et al. Clearance of Somatic Mutations at Remission and the Risk of Relapse in Acute Myeloid Leukemia. J Clin Oncol 2018; 36 (18) 1788-1797
    CrossrefPubMedGoogle Scholar
  • 60 Press RD, Eickelberg G, Froman A. et al. Next-generation sequencing-defined minimal residual disease before stem cell transplantation predicts acute myeloid leukemia relapse. Am J Hematol 2019; 94 (08) 902-912
    CrossrefPubMedGoogle Scholar
  • 61 Hourigan CS, Dillon LW, Gui G. et al. Impact of Conditioning Intensity of Allogeneic Transplantation for Acute Myeloid Leukemia With Genomic Evidence of Residual Disease. J Clin Oncol 2020; 38 (12) 1273-1283
    CrossrefPubMedGoogle Scholar
  • 62 Balagopal V, Hantel A, Kadri S. et al. Measurable residual disease monitoring for patients with acute myeloid leukemia following hematopoietic cell transplantation using error corrected hybrid capture next generation sequencing. PLoS One 2019; 14 (10) e0224097
    CrossrefPubMedGoogle Scholar
  • 63 Onecha E, Linares M, Rapado I. et al. A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia. Haematologica 2019; 104 (02) 288-296
    CrossrefPubMedGoogle Scholar
  • 64 Patkar N, Kakirde C, Shaikh AF. et al. Clinical impact of panel-based error-corrected next generation sequencing versus flow cytometry to detect measurable residual disease (MRD) in acute myeloid leukemia (AML). Leukemia 2021; 35 (05) 1392-1404
    CrossrefPubMedGoogle Scholar
  • 65 Ghannam J, Dillon LW, Hourigan CS. Next-generation sequencing for measurable residual disease detection in acute myeloid leukaemia. Br J Haematol 2020; 188 (01) 77-85
    CrossrefPubMedGoogle Scholar
  • 66 Yoest JM, Shirai CL, Duncavage EJ. Sequencing-based measurable residual disease testing in acute myeloid leukemia. Front Cell Dev Biol 2020; 8: 249
    CrossrefPubMedGoogle Scholar
  • 67 Vonk CM, Al Hinai ASA, Hanekamp D, Valk PJM. Molecular minimal residual disease detection in acute myeloid leukemia. Cancers (Basel) 2021; 13 (21) 5431
    CrossrefPubMedGoogle Scholar
  • 68 Hasserjian RP, Steensma DP, Graubert TA, Ebert BL. Clonal hematopoiesis and measurable residual disease assessment in acute myeloid leukemia. Blood 2020; 135 (20) 1729-1738
    CrossrefPubMedGoogle Scholar
  • 69 Ritterhouse LL, Parilla M, Zhen CJ. et al. Clinical validation and implementation of a measurable residual disease assay for NPM1 in acute myeloid leukemia by error-corrected next-generation sequencing. Mol Diagn Ther 2019; 23 (06) 791-802
    CrossrefPubMedGoogle Scholar
  • 70 Levis MJ, Perl AE, Altman JK. et al. A next-generation sequencing-based assay for minimal residual disease assessment in AML patients with FLT3-ITD mutations. Blood Adv 2018; 2 (08) 825-831
    CrossrefPubMedGoogle Scholar
  • 71 Bibault JE, Figeac M, Hélevaut N. et al. Next-generation sequencing of FLT3 internal tandem duplications for minimal residual disease monitoring in acute myeloid leukemia. Oncotarget 2015; 6 (26) 22812-22821
    CrossrefPubMedGoogle Scholar
  • 72 Blätte TJ, Schmalbrock LK, Skambraks S. et al. getITD for FLT3-ITD-based MRD monitoring in AML. Leukemia 2019; 33 (10) 2535-2539
    CrossrefPubMedGoogle Scholar
  • 73 Shih LY, Huang CF, Wu JH. et al. Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse. Blood 2002; 100 (07) 2387-2392
    CrossrefPubMedGoogle Scholar
  • 74 Garg M, Nagata Y, Kanojia D. et al. Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse. Blood 2015; 126 (22) 2491-2501
    CrossrefPubMedGoogle Scholar
  • 75 Patkar N, Bhanshe P, Rajpal S. et al. NARASIMHA: novel assay based on targeted RNA sequencing to identify ChiMeric gene fusions in hematological malignancies. Blood Cancer J 2020; 10 (05) 50
    CrossrefPubMedGoogle Scholar
  • 76 Dillon LW, Hayati S, Roloff GW. et al. Targeted RNA-sequencing for the quantification of measurable residual disease in acute myeloid leukemia. Haematologica 2019; 104 (02) 297-304
    CrossrefPubMedGoogle Scholar
  • 77 Kim T, Moon JH, Ahn JS. et al. RNA sequencing as an alternative tool for detecting measurable residual disease in core-binding factor acute myeloid leukemia. Sci Rep 2020; 10 (01) 20119
    CrossrefPubMedGoogle Scholar
  • 78 Zhou Y, Wood BL. Methods of detection of measurable residual disease in AML. Curr Hematol Malig Rep 2017; 12 (06) 557-567
    CrossrefPubMedGoogle Scholar
  • 79 Döhner H, Wei AH, Appelbaum FR. et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022; 140 (12) 1345-1377
    CrossrefPubMedGoogle Scholar
  • 80 Short NJ, Zhou S, Fu C. et al. Association of measurable residual disease with survival outcomes in patients with acute myeloid leukemia: a systematic review and meta-analysis. JAMA Oncol 2020; 6 (12) 1890-1899
    CrossrefPubMedGoogle Scholar
  • 81 Aitken MJL, Ravandi F, Patel KP, Short NJ. Prognostic and therapeutic implications of measurable residual disease in acute myeloid leukemia. J Hematol Oncol 2021; 14 (01) 137
    CrossrefPubMedGoogle Scholar
  • 82 Short NJ, Patel KP, Albitar M. et al. Targeted next-generation sequencing of circulating cell-free DNA vs bone marrow in patients with acute myeloid leukemia. Blood Adv 2020; 4 (08) 1670-1677
    CrossrefPubMedGoogle Scholar
  • 83 Nakamura S, Yokoyama K, Shimizu E. et al. Prognostic impact of circulating tumor DNA status post-allogeneic hematopoietic stem cell transplantation in AML and MDS. Blood 2019; 133 (25) 2682-2695
    CrossrefPubMedGoogle Scholar
  • 84 Rausch C, Rothenberg-Thurley M, Buerger SA. et al. Double dropoff droplet digital PCR: a novel, versatile tool for mutation screening and residual disease monitoring in acute myeloid leukemia using cellular or cell-free DNA. J Mol Diagn 2021; 23 (08) 975-985
    PubMedGoogle Scholar