Maria Ilaria Del Principe
  • Maria Ilaria Del Principe
    1Ematologia, Dipartimento di Biomedicina e Prevenzione Università degli Studi di Roma "Tor Vergata", Roma, Italia., Italy |


Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients’ risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy. Therefore, MRD might serve as an independent, additional biomarker to help identifying patients at higher risk of relapse. Detection of MRD requires the use of highly sensitive ancillary techniques, such as polymerase chain reaction (PCR) and multiparametric flow cytometry (MPFC). In the present manuscript, we will review the current approaches to investigate MRD and its clinical applications in AML management.


acute myeloid leukemia, minimal residual disease, flow cytometry, PCR, prognosis

Full Text:

Submitted: 2016-06-24 22:12:20
Published: 2016-10-20 00:00:00
Search for citations in Google Scholar
Related articles: Google Scholar


Estey EH. Acute myeloid leukemia: 2013 update on risk stratification and management. Am J Hematolol. 2013; 88(4): 318-327

Ferrara F, Schiffer CA: Acute myeloid leukemia in adults. Lancet 2013; 381: 484-495

Lowenberg B. Strategies in the treatment of acute myeloid leukemia. Haematologica 2004; 89: 1029-1032

Chen X, Xie H, Wood BL, Walter RB, Pagel JM, Becker PS, Sandhu VK, Abkowitz JL, Appelbaum FR, Estey EH. Relation of clinical response and minimal residual disease and their prognostic impact on outcome in acute myeloid leukemia. J ClinOncol. 2015; 33(11):1258-1264

Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European Leukemia Net. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European Leukemia Net.Blood. 2010;115(3):453-474

Kayser S, Walter RB, Stock W, Schlenk RF. Minimal residual disease in acute myeloid leukemia-current status and future perspectives. Curr Hematol Malig Rep. 2015;10(2):132-144

Grimwade D, Freeman SD. Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for "prime time"? Blood. 2014;124(23):3345-3355

Chou WC, Tang JL, Wu SJ, Tsay W, Yao M, Huang SY, Huang KC, Chen CY, Huang CF, Tien HF. Clinical implications of minimal residual disease monitoring by quantitative polymerase chain reaction in acute myeloid leukemia patients bearing nucleophosmin (NPM1) mutations. Leukemia 2007; 21(5): 998-1004

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

Cilloni D, Renneville A, Hermitte F, Robert K. Hills RK, Daly S, JovanovicJV,Gottardi E, Fava M, Schnittger S, Weiss T, Izzo B, Nomdedeu J, van der Heijden A, van der Reijden BA, Jansen JH,. van der Velden VHJ, Ommen H, Preudhomme C, Saglio G, Grimwade D. Real-Time Quantitative Polymerase Chain Reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: A European Leukemia Net Study. J Clin Oncol. 2009; 27(31): 5195-5201

Scholl C, Breitinger H, Schlenk RF, Döhner H, Fröhling S, Döhner K;.Development of a real-time RT-PCR assay for the quantification of the most frequent MLL/AF9 fusion types resulting from translocation t(9;11)(p22;q23) in acute myeloid leukemia. Genes, Chromosomes Cancer. 2003; 38(3): 274-280

Scholl C, Schlenk RF, Eiwen K, Döhner H, Fröhling S, Döhner K; AML Study GroupThe prognostic value of MLL-AF9 detection in patients with t(9;11)(p22;q23)-positive acute myeloid leukemia. Haematologica.2005; 90(12): 1626-1634

Perea G, Lasa A, Aventín A, Domingo A, Villamor N, Queipo de Llano MP, Llorente A, Juncà J, Palacios C, Fernández C, Gallart M, Font L, Tormo M, Florensa L, Bargay J, Martí JM, Vivancos P, Torres P, Berlanga JJ, Badell I, Brunet S, Sierra J, Nomdedéu JF; GrupoCooperativo para el Estudio y Tratamiento de las LeucemiasAgudas y Miel. Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia with favorable cytogenetics [t(8;21) and inv(16)]. Leukemia 2006; 20(1): 87-94

Martinelli G, Rondoni M, Buonamici S, Ottaviani E, Piccaluga PP, Malagola M, Baccarani M. Molecular monitoring to identify a threshold of CBFbeta/MYH11 transcript below which continuous complete remission of acute myeloid leukemia inv16 is likely. Haematologica. 2004;89:495-497

Corbacioglu A, Scholl C, Schlenk RF, Eiwen K, Du J, Bullinger L, Fröhling S, Reimer P, Rummel M, Derigs HG, Nachbaur D, Krauter J, Ganser A, Döhner H, Döhner KPrognosticimpact of minimal residual disease in CBFB-MYH11-positive acute myeloid leukemia. J Clin Oncol. 2010;28:3724-3729

Jourdan E, Boissel N, Chevret S, Delabesse E, Renneville A, Cornillet P, Blanchet O, Cayuela JM, Recher C, Raffoux E, Delaunay J, Pigneux A, Bulabois CE, Berthon C, Pautas C, Vey N, Lioure B, Thomas X, Luquet I, Terré C, Guardiola P, Béné MC, Preudhomme C, Ifrah N, Dombret H; 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

Schnittger S, Weisser M, Schoch C, HiddemannW, Haferlach T, Kern W. New score predicting for prognosis in PML-RARA1, AML1-ETO1, or CBFBMYH111 acute myeloid leukemia based on quantification of fusion transcripts. Blood. 2003;102(8):2746-2755

Leroy H, de Botton S, Grardel-Duflos N, Darre S, Leleu X, Roumier C, Morschhauser F, Lai JL, Bauters F, Fenaux P, Preudhomme C. Prognostic value of real-time quantitative PCR(RQ-PCR) in AML with t(8;21). Leukemia. 2005;19(3):367-372

Zhu HH, Zhang XH, Qin YZ, Liu DH, Jiang H, Chen H, Jiang Q, Xu LP, Lu J, Han W, Bao L, Wang Y, Chen YH, Wang JZ, Wang FR, Lai YY, Chai JY, Wang LR, Liu YR, Liu KY, Jiang B, Huang XJ. 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

Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358(18):1909-1918

Grunwald MR, Levis MJ. FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance. Int J Hematol 2013; 97: 683-694

Cloos J, Goemans BF, Hess CJ, et al. Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples. Leukemia. 2006 ;20(7):1217-1220

Paietta E. Minimal residual disease in acute myeloid leukemia: coming of age. Hematol Educ Program. 2012; 2012: 35-42

Thol F, Kölking B, Damm F, Reinhardt K, Klusmann JH, Reinhardt D, von Neuhoff N, Brugman MH, Schlegelberger B, Suerbaum S, Krauter J, Ganser A, Heuser MNext-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations. Genes Chromosome Cancer. 2012; 51 (7): 689-695

Spencer DH, Abel HJ, Lockwood CM, Payton JE, Szankasi P, Kelley TW, Kulkarni S, Pfeifer JD, Duncavage EJ. Detection of FLT3 internal tandem duplication in targeted, short-read-length, next-generation sequencing data. J Mo lDiagn. 2013;15(1):81-93

Bibault JE, Figeac M, Hélevaut N, Rodriguez C, Quief S, Sebda S, Renneville A, Nibourel O, Rousselot P, Gruson B, Dombret H, Castaigne S, Preudhomme C. Next-generation sequencing of FLT3 internal tandem duplications for minimal residual disease monitoring in acute myeloid leukemia. Oncotarget. 2015 6(26):22812-22821

Zuffa E, Franchini E, Papayannidis C, Baldazzi C, Simonetti G, Testoni N, Abbenante MC, Paolini S, Sartor C, Parisi S, Marconi G, Cattina F, Bochicchio MT, Venturi C, Ottaviani E, Cavo M, Martinelli G1Revealing very small FLT3 ITD mutated clones by ultra-deep sequencing analysis has important clinical implications in AML patients. Oncotarget. 2015;;6(31):31284-94

Gorello P, Cazzaniga G, Alberti F, Dell'Oro MG, Gottardi E, Specchia G, Roti G, Rosati R, Martelli MF, Diverio D, Lo Coco F, Biondi A, Saglio G, Mecucci C, Falini B: Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations. Leukemia 2006; 20:1103-1108

Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L, La Starza R, Diverio D, Colombo E, Santucci A, Bigerna B, Pacini R, Pucciarini A, Liso A, Vignetti M, Fazi P, Meani N, Pettirossi V, Saglio G, Mandelli F, Lo-Coco F, Pelicci PG, Martelli MF; GIMEMA Acute Leukemia Working Party.Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype.NEngl J Med. 2005;352(3):254-266

Kramer M, Bornhäuser M, Schaich M, Schetelig J, Platzbecker U, Röllig C, Heiderich C, Landt O, Ehninger G, Thiede C; 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(1):83-92

Schnittger S, Kern W, Tschulik C, Weiss T, Dicker F, Falini B, Haferlach C, Haferlach T. Minimal residual disease levels assessed by NPM1 mutation-specific RQ-PCR provide important prognostic information in AML.Blood. 2009;114(11):2220-2231

Krönke J, Schlenk RF, Jensen KO, Tschürtz F, Corbacioglu A, Gaidzik VI, Paschka P, Onken S, Eiwen K, Habdank M, Späth D, Lübbert M, Wattad M, Kindler T, Salih HR, Held G, Nachbaur D, von Lilienfeld-Toal M, Germing U, Haase D, Mergenthaler HG, Krauter J, Ganser A, Göhring G, Schlegelberger B, Döhner H, Döhner K. 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

Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, Patel Y, Bhudia N, Farah H, Mason J, Wall K, Akiki S, Griffiths M, Solomon E, McCaughan F, Linch DC, Gale RE, Vyas P, Freeman SD, Russell N, Burnett AK, Grimwade D; UK National Cancer Research Institute AML Working Group. Assessment of Minimal Residual Disease in Standard-Risk AML.N Engl J Med.2016;374(5):422-433

Ley T , Ding L, Walter M, McLellan MD, Lamprecht T, Larson DE, Kandoth C, Payton JE, Baty J, Welch J, Harris CC, Lichti CF, Townsend RR, Fulton RS, Dooling DJ, Koboldt DC, Schmidt H, Zhang Q, Osborne JR, Lin L, O'Laughlin M, McMichael JF, Delehaunty KD, McGrath SD, Fulton LA, Magrini VJ, Vickery TL, Hundal J, Cook LL, Conyers JJ, Swift GW, Reed JP, Alldredge PA, Wylie T, Walker J, Kalicki J, Watson MA, Heath S, Shannon WD, Varghese N, Nagarajan R, Westervelt P, Tomasson MH, Link DC, Graubert TA, DiPersio JF, Mardis ER, Wilson RK. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010; 363 (25): 2424-2433

Yan XJ, Xu J, Gu ZH,Pan CM, Lu G, Shen Y, Shi JY, Zhu YM, Tang L, Zhang XW, Liang WX, Mi JQ, Song HD, Li KQ, Chen Z, Chen SJ.. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet. 2011; 43(4): 309-315

Pløen GG, Nederby L, Guldberg P, Hansen M, Ebbesen LH, Jensen UB, Hokland P, Aggerholm A. Persistence of DNMT3A mutations at long-term remission in adult patients with AML. Br J Haematol. 2014; 167 (4): 478-486

Nomdedéu JF, Hoyos M, Carricondo M, Bussaglia E, Estivill C, Esteve J, Tormo M, Duarte R, Salamero O, de Llano MP, García A, Bargay J, Heras I, Martí-Tutusaus JM, Llorente A, Ribera JM, Gallardo D, Aventin A, Brunet S, Sierra J; CETLAM Group. Bone marrow WT1 levels at diagnosis, post-induction and post-intensification in adult de novo AML. Leukemia.2013;27(11):2157-2164

Lambert J, Lambert J, Nibourel O, Pautas C, Hayette S, Cayuela JM, Terré C, Rousselot P, Dombret H, Chevret S, Preudhomme C, Castaigne S, Renneville A. MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumabozogamicin. Oncotarget. 2014;5(15):6280-6288

Rossi G1, Minervini MM, Melillo L, di Nardo F, de Waure C, Scalzulli PR, Perla G, Valente D, Sinisi N, Cascavilla N. Predictive role of minimal residual disease and log clearance in acute myeloid leukemia: a comparison between multiparameter flow cytometry and Wilm's tumor 1 levels. Ann Hematol. 2014;93(7):1149-1157

Zhong L, Wei L, Chen J, Huang X, Gong Y, Lu Y. WT1 expression in circulating RNA as a minimal residual disease marker for AML patients after stem cell transplantation. MolDiagnTher 2015 ;19(4):205-212

Zhang R, Yang JY, Sun HQ, Jia H, Liao J, Shi YJ, Li G. Comparison of minimal residual disease (MRD) monitoring by WT1 quantification between childhood acute myeloid leukemia and acute lymphoblastic leukemia. Eur Rev Med Pharmacol Sci. 2015;19(14):2679-2688

Hasle H, Kjeldsen E, Hokland P.WT1 gene expression: an excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukemia patients: results from a single centre study. Br J Haematol. 2004;125(5):590-600

Ommen HB, Nyvold CG, Braendstrup K, Andersen BL, Ommen IB, Hasle H, Hokland P, Ostergaard M. Relapse prediction in acute myeloid leukaemia patients in complete remission using WT1 as a molecular marker: development of a mathematical model to predict time from molecular to clinical relapse and define optimal sampling intervals. Br J Haematol. 2008;141(6):782-791

Goswami M, McGowan KS, Lu K, Jain N, Candia J, Hensel NF, Tang J, Calvo KR, Battiwalla M, Barrett AJ, Hourigan CS. A multigene array for measurable residual disease detection in AML patients undergoing SCT. Bone Marrow Transplant. 2015;50(5):642-651

Ossenkoppele GJ, van de Loosdrecht AA, Schuurhuis GJ Review of the relevance of aberrant antigen expression by flow cytometry in myeloid neoplasms.Br J Haematol. 2011 May;153(4):421-436

San Miguel JF, Vidriales MB, Lopez-Berges C López-Berges C, Díaz-Mediavilla J, Gutiérrez N, Cañizo C, Ramos F, Calmuntia MJ, Pérez JJ, González M, Orfao A. Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to postinduction treatment stratification. Blood 2001; 98(6): 1746-1751

Olaru D, Campos L, Flandrin P, Nadal N, Duval A, Chautard S, Guyotat D. Multiparametric analysis of normal and postchemotherapy bone marrow: Implication for the detection of leukemia-associated immunophenotypes. Cytometry B ClinCytom. 2008;74(1):17-24

Macedo A, Orfao A, Ciudad J, Gonzalez M, Vidriales B, Lopez-BergesMC, Martinez A, Landolfi C, Canizo C, San Miguel JF. Phenotypicanalysis of CD34 subpopulations in normal human bone marrowand its application for the detection of minimal residual disease.Leukemia 1995;9:1896–1901

Béné MC, Nebe T, Bettelheim P, Buldini B, Bumbea H, Kern W, Lacombe F, Lemez P, Marinov I, Matutes E, Maynadié M, Oelschlagel U, Orfao A, Schabath R, Solenthaler M, Tschurtschenthaler G, Vladareanu AM, Zini G, Faure GC, Porwit A. Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10.Leukemia. 2011;25(4):567-574

Johansson U, Bloxham D, Couzens S, Jesson J, Morilla R, Erber W, Macey M; British Committee for Standards in Haematology. Guidelines on the use of multicolour flow cytometry in the diagnosis of haematological neoplasms. British Committee for Standards in Haematology.Br J Haematol. 2014 ;165(4):455-488

San Miguel JF, Martinez a, MacedoA, Vidriales MB, Lopez-Berges C,Gonzalez M, Caballero D, Garcıa-Marcos M a, Ramos F, Fernandez-Calvo J, Calmuntia MJ, Diaz-Mediavilla J, Orfao A. Immunophenotyping investigation of minimal residual disease is a useful approach forpredicting relapse in acute myeloid leukemia patients. Blood 1997;90:2465–2470

Kern W, Schnittger S. Monitoring of acute myeloid leukemia by flow cytometry. CurrOncol Rep. 2003;5:405–412

Venditti A, Buccisano F, Del Poeta G, Maurillo L, Tamburini A, Cox C, Battaglia A, Catalano G, Del Moro B, Cudillo L, Postorino M, Masi M, Amadori S. Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia: Presented inpart at the 41st Annual Meeting of the American Society of Hematology, December 3–7, 1999, New Orleans, LA. Blood 2000;96:3948–3952

Kern W, Voskova D, Schoch C, Hiddemann W, Schnittger S, Haferlach T. Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia. Blood 2004;104:3078–3085

Kern W, Haferlach T, Schoch C, Loffler H, Gassmann W, Heinecke A, Sauerland MC, Berdel W, Buchner T, Hiddemann W.Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial. Blood 2003; 101, 64-70

Gianfaldoni G, Mannelli F, Bencini S, Leoni F, Baldini S, Bosi A. Peripheral blood blast clearance during induction therapy in acute myeloid leukemia. Blood. 2008;111:1746-1747

Elliott MA, Litzow MR, Letendre LL, Wolf RC, Hanson CA, Tefferi A, Tallman MS.Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival. Blood. 2007;110:4172-4174

Maurillo L, Buccisano F, Piciocchi A, Del Principe MI, Sarlo C, Di Veroli A, Panetta P, Irno-Consalvo M, Nasso D, Ditto C, Refrigeri M, De Angelis G, Cerretti R, Arcese W, Sconocchia G, Lo-Coco F, Amadori S, Venditti A. Minimal residual disease as biomarker for optimal biologic dosing of ARA-C in patients with acute myeloid leukemia.Am J Hematol. 2015 Feb;90(2):125-131

Köhnke T, Sauter D, Ringel K, Hoster E, Laubender RP, Hubmann M, Bohlander SK, Kakadia PM,Schneider S, Dufour A, Sauerland M-C, Berdel WE, Büchner T, Wörmann B, Braess J, Hiddemann W, Spiekermann K, Subklewe M. Early assessment of minimal residua ldisease in AML by flowcytometry during aplasia identifies patients at increased riskof relapse. Leukemia 2014; 1-10

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; 76, 91-101

Terwijn M, van Putten WL, Kelder A, van der Velden VH, Brooimans RA, Pabst T, Maertens J, Boeckx N, de Greef GE, Valk PJ, Preijers FW, Huijgens PC, Dräger AM, Schanz U, Jongen-Lavrecic M, Biemond BJ, Passweg JR, van Gelder M, Wijermans P, Graux C, Bargetzi M, Legdeur MC, Kuball J, de Weerdt O, Chalandon Y, Hess U, Verdonck LF, Gratama JW, Oussoren YJ, Scholten WJ, Slomp J, Snel AN, Vekemans MC, Löwenberg B, Ossenkoppele GJ, Schuurhuis GJ. J Clin Oncol. 2013;31(31):3889-3897

Freeman SD, Virgo P, Couzens S, Grimwade D, Russell N, Hills RK, Burnett AK 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):4123-4131

Venditti A, Buccisano F, Del Poeta G, Maurillo L, Tamburini A, Cox C, Battaglia A, Catalano G, Del Moro B, Cudillo L, Postorino M, Masi M, Amadori S.Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood 2000; 96, 3948-3952

Buccisano F, Maurillo L, Gattei V, Del Poeta G, Del Principe MI, Cox MC, Panetta P, Consalvo MI, Mazzone C, Neri B, Ottaviani L, Fraboni D, Tamburini A, Lo-Coco F, Amadori S, Venditti A The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia. Leukemia 2006; 20, 1783-1789

Maurillo L, Buccisano F, Del Principe MI, Sarlo C, Di Caprio L, Ditto C, Giannotti F, Nasso D, Ceresoli E, Postorino M, Refrigeri M, Amadori S, Venditti A.. Toward Optimization of Postremission Therapy for Residual Disease-Positive Patients With Acute Myeloid Leukemia. J Clin Oncol 2008; 26:4944-4951

Walter RB, Buckley SA, Pagel JM, Wood BL, Storer BE, Sandmaier BM,Fang M, Gyurkocza B, Delaney C, Radich JP, Estey EH, Appelbaum FR. Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission. Blood. 2013; 122(10):1813–1821

Walter RB, Gyurkocza B, Storer BE, Godwin CD, Pagel JM, Buckley SA, Sorror ML, Wood BL, Storb R, Appelbaum FR, Sandmaier BM. 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): 137-144

Zhou Y, Othus M, Araki D, Wood BL, Radich JP, Halpern AB, Mielcarek M, Estey EH, Appelbaum FR, Walter RB. Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia. Leukemia. 2016 doi: 10.1038/leu.2016.46. [Epub ahead of print]

Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Ludwig WD, Serve H, Reichle A, Peceny R, Oruzio D, Schmid C, Schiel X, Hentrich M, Sauerland C, Unterhalt M, Fiegl M, Kern W, Buske C, Bohlander S, Heinecke A, Baurmann H, Beelen DW, Berdel WE, Büchner T, Hiddemann W. Dose-dense induction with sequential high-dose cytarabine and mitoxantone (S-HAM) and pegfilgrastim results in a high efficacy and a short duration of critical neutropenia in de novo acute myeloid leukemia: a pilot study of the AMLCG. Blood 2009; 113, 3903-3910

Schaich M, Illmer T, Aulitzky WE, BornhaeuserM, GriesshammerM, s Haenel M, Ho AD, Link H, Neubauer A, Schmitz N, Serve H, Thiede C, Thiel E, WagnerT, WandtH, BerdelW, GEhninger G on behalf of the Study Alliance Leukemia (SAL)Upfront Allogeneic Stem Cell Transplantation for Remission Induction in High-Risk Acute Myeloid Leukemia Patients within the Randomized Multi- Center Trial AML2003. Blood 2008; 112, 978a.

Buccisano F, Maurillo L, Piciocchi A, Del Principe MI, Sarlo C, Cefalo M, Ditto C, Di Veroli A, De Santis G, Irno Consalvo M, Fraboni D, Panetta P, Palomba P, Attrotto C, Del Poeta G, Sconocchia G, Lo-Coco F, Amadori S, Venditti A. Minimal residual disease negativity in elderly patients with acute myeloid leukemia may indicate different postremission strategies than in younger patients. Ann Hematol. 2015; 94(8):1319-1326

Buccisano F, Maurillo L, Del Principe MI, Del Poeta G, Sconocchia G, Lo-Coco F, Arcese W, Amadori S, Venditti A. Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia.Blood. 2012, 119, 332-341

Buccisano F, Maurillo L, Spagnoli A, Del Principe MI, Fraboni D, Panetta P, Ottone T, Consalvo MI, Lavorgna S, Bulian P, Ammatuna E, Angelini DF, Diamantini A, Campagna S, Ottaviani L, Sarlo C, Gattei V, Del Poeta G, Arcese W, Amadori S, Lo Coco F, Venditti ACytogenetic and molecular diagnostic characterization combined to post-consolidation minimal residual disease assessment by flow-cytometry improves risk stratification in adult acute myeloid leukemia. Blood. 2010;116:2295-2303


Langebrake C, Brinkmann I, Teigler-Schlegel A, CreutzigU, Griesinger F, Puhlmann U, Reinhardt D. Immunophenotypic differences between diagnosis and relapse in childhood AML: Implications for MRD monitoring. Cytometry B Clin Cytom 2005;63B:1–9

Baer MR, Stewart CC, Dodge RK, Leget G, Sule N, MrozekK,Schiffer CA, Powell BL, Kolitz JE, Moore JO, Stone RM, Davey FR, Carroll AJ, Larson RA, Bloomfield CD. High frequency of immunophenotype changes in acute myeloid leukemia at relapse: Implications for residual disease detection (Cancer and Leukemia Group B Study 8361). Blood 2001;97:3574–3580

Voskova D, Schoch C, Schnittger S, Hiddemann W, HaferlachT,Kern W. Stability of leukemia-associated aberrant immunophenotypes in patients with acute myeloid leukemia between diagnosis and relapse: comparison with cytomorphologic, cytogenetic, and molecular genetic findings. Cytometry B ClinCytom 2004;62B:25–38

Van der Velden VHJ, van der Sluijs-Geling A, Gibson BES, teMarvelde JG, Hoogeveen PG, Hop WCJ, Wheatley K, Bierings MB, Schuurhuis GJ, de Graaf SSN, van Wering ER, van Dongen JJM. Clinical significance of flow cytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol. Leukemia 2010;24:1599–1606

Bachas C, Schuurhuis GJ, Assaraf YG, Kwidama ZJ, Kelder A, Wouters F, Snel a N, Kaspers GJL, Cloos J. The role of minor subpopulations within the leukemic blast compartment of AML patients at initial diagnosis in the development of relapse. Leukemia 2012;26:1313–1320

Angelini DF, Ottone T, Guerrera G, Lavorgna S, Cittadini M, Buccisano F, De Bardi M, Gargano F, Maurillo L, Divona M, Noguera NI, Consalvo MI, Borsellino G, Bernardi G, Amadori S, Venditti A, Battistini L, Lo-Coco F. A Leukemia-Associated CD34/CD123/CD25/CD99+ Immunophenotype Identifies FLT3-Mutated Clones in Acute Myeloid Leukemia.Clin Cancer Res. 2015 1;21(17):3977-3985

Maurillo L, Buccisano F, Spagnoli A, Del Poeta G, Panetta P, Neri B, Del Principe MI, Mazzone C, Consalvo MI, Tamburini A, Ottaviani L, Fraboni D, Sarlo C, De Fabritiis P, Amadori S, Venditti A.Monitoring of minimal residual disease in adult acute myeloid leukemia using peripheral blood as an alternative source to bone marrow. Haematologica. 2007 ;92(5):605-611

Zeijlemaker W, Kelder A, Oussoren-Brockhoff YJ, Scholten WJ, Snel AN, Veldhuizen D, Cloos J, Ossenkoppele GJ, Schuurhuis GJ. Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia. Leukemia. 2016;30(3):708-715

Anguille S, Van Tendeloo VF, Berneman ZN. Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia. Leukemia. 2012;26(10):2186-2196

Terwijn M, Zeijlemaker W, Kelder A, Rutten AP, Snel AN, Scholten WJ, Pabst T, Verhoef G, Löwenberg B, Zweegman S, Ossenkoppele GJ, Schuurhuis GJ. Leukemic Stem Cell Frequency: A Strong Biomarker for Clinical Outcome in Acute Myeloid Leukemia. Plos One 2014; :e107587

Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD Jr, van Rooijen N, Weissman IL. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138(2): 286-299

van Rhenen A, van Dongen GA, Kelder A, Rombouts EJ, Feller N, Moshaver B, Stigter-van Walsum M, Zweegman S, Ossenkoppele GJ, Jan Schuurhuis G The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood. 2007 ;110(7):2659-2666

Will B, Steidl U. Multiparameter fluorescence-activated cell sorting and analysis of stem and progenitor cells in myeloid malignancies. Best Pract Res ClinHaematol. 2010; 23(3): 391-401

van Rhenen A, Moshaver B, Kelder A, Feller N, Nieuwint AW, Zweegman S, Ossenkoppele GJ, Schuurhuis GJ.Aberrant marker expression patterns on the CD34+CD38- stem cell compartment in acute myeloid leukemia allows to distinguish the malignant from the normal stem cell compartment both at diagnosis and in remission. Leukemia. 2007 ;21(8):1700-1707

van Rhenen A, Feller N, Kelder A, Westra AH, Rombouts E, Zweegman S, van der Pol MA, Waisfisz Q, Ossenkoppele GJ, Schuurhuis GJ.High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival.Clin Cancer Res. 2005;11(18):6520-6527

Zeijlemaker W, Kelder A, Oussoren-Brockhoff YJ, Scholten WJ, Snel AN, Veldhuizen D, Cloos J, Ossenkoppele GJ, Schuurhuis GJ. A simple one-tube assay for immunophenotypical quantification of leukemic stem cells in acute myeloid leukemia. Leukemia. 2016;30(2):439-446

Abstract views:


Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

Comments on this article

View all comments

Copyright (c) 2016 Mediterranean Journal of Hematology and Infectious Diseases

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
© PAGEPress 2008-2018     -     PAGEPress is a registered trademark property of PAGEPress srl, Italy.     -     VAT: IT02125780185     •     Privacy