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Future Developments: Measurable Residual Disease

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Acute Myeloid Leukemia

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

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Abstract

Measurable (previously minimal) residual disease (MRD) detection in acute myeloid leukemia (AML) has progressed beyond being a recognized strong prognostic factor. MRD-risk stratification is now incorporated into many treatment schedules and there is ongoing evaluation of MRD-directed therapy. Evolving assay technology such as next-generation sequencing has resulted in an increased repertoire of potential molecular biomarkers for MRD but molecular MRD can be challenging in AML, particularly in older adults, due to the oligoclonal profile of leukemic and co-existing pre-leukemic progenitors. Evaluation of different MRD markers/assays has also extended to assessing the therapeutic efficacy of novel drugs. How MRD assessments pre- and post-transplant should guide the delivery of allogeneic transplant and peri-transplant interventions to reduce relapse remains a key question but recent studies contribute important additional information. This review will update on what has been happening in these different areas and consider prospects for the future use and interpretation of MRD in the setting of trials and routine clinical practice.

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References

  • Amatangelo MD, Quek L, Shih A et al (2017) Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response. Blood 130:732–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Araki D, Wood BL, Othus M et al (2016) Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: time to move toward a minimal residual disease-based definition of complete remission? J Clin Oncol 34:329–336

    Article  PubMed  Google Scholar 

  • Assi R, Kantarjian H, Ravandi F et al (2018) Immune therapies in acute myeloid leukemia: a focus on monoclonal antibodies and immune checkpoint inhibitors. Curr Opin Hematol 25:136–145

    Article  CAS  PubMed  Google Scholar 

  • Balsat M, Renneville A, Thomas X et al (2017) 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 35:185–193

    Article  CAS  PubMed  Google Scholar 

  • Blatte TJ, Schmalbrock LK, Skambraks S et al (2019) getITD for FLT3-ITD-based MRD monitoring in AML. Leukemia 33(10):2535–2539

    Article  PubMed  PubMed Central  Google Scholar 

  • Boddu P, Jorgensen J, Kantarjian H et al (2018) Achievement of a negative minimal residual disease state after hypomethylating agent therapy in older patients with AML reduces the risk of relapse. Leukemia 32:241–244

    Article  CAS  PubMed  Google Scholar 

  • Buccisano F, Maurillo L, Del Principe MI et al (2012) Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia. Blood 119:332–341

    Article  CAS  PubMed  Google Scholar 

  • Buccisano F, Maurillo L, Piciocchi A et al (2015) Minimal residual disease negativity in elderly patients with acute myeloid leukemia may indicate different postremission strategies than in younger patients. Ann Hematol 94:1319–1326

    Article  CAS  PubMed  Google Scholar 

  • Buccisano F, Maurillo L, Piciocchi A et al (2017) Pre-transplant persistence of minimal residual disease does not contraindicate allogeneic stem cell transplantation for adult patients with acute myeloid leukemia. Bone Marrow Transplant 52:473–475

    Article  CAS  PubMed  Google Scholar 

  • Buccisano F, Dillon R, Freeman SD et al (2018) Role of minimal (measurable) residual disease assessment in older patients with acute myeloid leukemia. Cancers (Basel) 10:215

    Article  CAS  Google Scholar 

  • Buckley SA, Wood BL, Othus M et al (2017) Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis. Haematologica 102:865–873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bullinger L, Dohner K, Dohner H (2017) Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol 35:934–946

    Article  CAS  PubMed  Google Scholar 

  • Burchert A, Bug G, Finke J et al (2018) Sorafenib as maintenance therapy post allogeneic stem cell transplantation for FLT3-ITD positive AML: results from the randomized, double-blind, placebo-controlled multicentre Sormain trial. Blood 132(Suppl 1):661–661

    Article  Google Scholar 

  • Burnett AK, Russell NH, Hills RK et al (2012) Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol 30:3924–3931

    Article  CAS  PubMed  Google Scholar 

  • Cocciardi S, Dolnik A, Kapp-Schwoerer S et al (2019) Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation. Nat Commun 10:2031

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cornelissen JJ, Gratwohl A, Schlenk RF et al (2012) The European LeukemiaNet AML working party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol 9:579–590

    Article  CAS  PubMed  Google Scholar 

  • Daver N, Kantarjian H, Garcia-Manero G et al (2017) Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Haematologica 102:1709–1717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dillon R, Hills RK, Freeman SD et al (2020) Molecular MRD status and outcome after transplantation in NPM1 mutated AML: results from the UK NCRI AML17 study. Blood 135(9):680–688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DiNardo CD, Stein EM, de Botton S et al (2018) Durable remissions with Ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med 378:2386–2398

    Article  CAS  PubMed  Google Scholar 

  • DiNardo CD, Stein AS, Stein EM et al (2019a) Mutant IDH1 inhibitor ivosidenib (IVO; AG-120) in combination with azacitidine (AZA) for newly diagnosed acute myeloid leukemia (ND AML). J Clin Oncol 37(15 suppl):7011–7011

    Article  Google Scholar 

  • DiNardo CD, Schuh AC, Stein EM et al (2019b) Enasidenib plus Azacitidine significantly improves complete remission and overall response compared with Azacitidine alone in patients with newly diagnosed acute myeloid leukemia (AML) with isocitrate dehydrogenase 2 (IDH2) mutations: interim phase II results from an ongoing, randomized study. Blood 134(Suppl 1):643–643

    Article  Google Scholar 

  • DiNardo CD, Pratz K, Pullarkat V et al (2019c) Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood 133:7–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DiNardo CD, Tiong IS, Quaglieri A et al (2020) Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML. Blood 135(11):791–803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dohner H, Estey E, Grimwade D et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129:424–447

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Döhner K, Thiede C, Jahn N et al (2020) Impact of NPM1/FLT3-ITD genotypes defined by the2017 European LeukemiaNet in patients with acute myeloid leukemia. Blood 135(5):371–380

    Article  PubMed  PubMed Central  Google Scholar 

  • Ferret Y, Boissel N, Helevaut N et al (2018) Clinical relevance of IDH1/2 mutant allele burden during follow-up in acute myeloid leukemia. A study by the French ALFA Group. Haematologica 103:822–829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fournier E, Duployez N, Ducourneau B et al (2020) Mutational profile and benefit of gemtuzumab ozogamicin in acute myeloid leukemia patients treated in the ALFA0701 trial. Blood 135(8):542–546

    Article  PubMed  Google Scholar 

  • Freeman SD, Hourigan CS (2019) MRD evaluation of AML in clinical practice: are we there yet? Hematology Am Soc Hematol Educ Program 2019:557–569

    Article  PubMed  PubMed Central  Google Scholar 

  • Freeman SD, Virgo P, Couzens S et al (2013) Prognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia. J Clin Oncol 31:4123–4131

    Article  PubMed  Google Scholar 

  • Freeman SD, Hills RK, Virgo P et al (2018) Measurable residual disease at induction redefines partial response in acute myeloid leukemia and stratifies outcomes in patients at standard risk without NPM1 mutations. J Clin Oncol 36:1486–1497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Genovese G, Kahler AK, Handsaker RE et al (2014) Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 371:2477–2487

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gerstung M, Papaemmanuil E, Martincorena I et al (2017) Precision oncology for acute myeloid leukemia using a knowledge bank approach. Nat Genet 49:332–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Getta BM, Devlin SM, Levine RL et al (2017) 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 23:1064–1071

    Article  CAS  PubMed  Google Scholar 

  • Gilleece MH, Labopin M, Yakoub-Agha I et al (2018) Measurable residual disease, conditioning regimen intensity, and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: a registry analysis of 2292 patients by the acute leukemia working party European Society of Blood and Marrow Transplantation. Am J Hematol 93:1142–1152

    Article  PubMed  Google Scholar 

  • Goldberg AD, Talati C, Desai P et al (2018) TP53 mutations predict poorer responses to CPX-351 in acute myeloid leukemia. Blood 132(Suppl 1):1433–1433

    Article  Google Scholar 

  • Grimwade D, Ivey A, Huntly BJ (2016) Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood 127:29–41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guenot C, Lacombe F, Allou K et al (2019) Peripheral blood minimal/measurable residual disease assessed in flow cytometry in acute myeloblastic leukemia. Leukemia 33(7):1814–1816

    Article  PubMed  Google Scholar 

  • Haubner S, Perna F, Kohnke T et al (2019) Coexpression profile of leukemic stem cell markers for combinatorial targeted therapy in AML. Leukemia 33:64–74

    Article  CAS  PubMed  Google Scholar 

  • Hills RK, Castaigne S, Appelbaum FR et al (2014) Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol 15:986–996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirsch P, Tang R, Abermil N et al (2017) Precision and prognostic value of clone-specific minimal residual disease in acute myeloid leukemia. Haematologica 102:1227–1237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hochman MJ, Othus M, Shaw C et al (2019) Does intensity of induction chemotherapy affect the impact of measurable residual disease (MRD) on prognosis in acute myeloid leukemia (AML)? J Clin Oncol 37(15 suppl):7031–7031

    Article  Google Scholar 

  • Hoffmann H, Thiede C, Glauche I et al (2019) The prognostic potential of monitoring disease dynamics in NPM1-positive acute myeloid leukemia. Leukemia 33(6):1531–1534

    Article  CAS  PubMed  Google Scholar 

  • Hollein A, Jeromin S, Meggendorfer M et al (2018a) Minimal residual disease (MRD) monitoring and mutational landscape in AML with RUNX1-RUNX1T1: a study on 134 patients. Leukemia 32:2270–2274

    Article  PubMed  CAS  Google Scholar 

  • Hollein A, Meggendorfer M, Dicker F et al (2018b) NPM1 mutated AML can relapse with wild-type NPM1: persistent clonal hematopoiesis can drive relapse. Blood Adv 2:3118–3125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hourigan CS, Goswami M, Battiwalla M et al (2016) When the minimal becomes measurable. J Clin Oncol 34:2557–2558

    Article  PubMed  Google Scholar 

  • Hourigan CS, Gale RP, Gormley NJ et al (2017) Measurable residual disease testing in acute myeloid leukaemia. Leukemia 31:1482–1490

    Article  CAS  PubMed  Google Scholar 

  • Hourigan CS, Dillon LW, Gui G et al (2020) Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease. J Clin Oncol 38(12):1273–1283

    Article  CAS  PubMed  Google Scholar 

  • Ivey A, Hills RK, Simpson MA et al (2016) Assessment of minimal residual disease in standard-risk AML. N Engl J Med 374:422–433

    Article  CAS  PubMed  Google Scholar 

  • Jaiswal S, Fontanillas P, Flannick J et al (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371:2488–2498

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jongen-Lavrencic M, Grob T, Hanekamp D et al (2018) Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med 378:1189–1199

    Article  CAS  PubMed  Google Scholar 

  • Kadia TM, Cortes JE, Konopleva MY et al (2019) Venetoclax combined with Cladribine + low dose AraC (LDAC) alternating with 5-Azacytidine produces high rates of minimal residual disease (MRD) negative complete remissions (CR) in older patients with newly diagnosed acute myeloid leukemia (AML). Blood 134:2647–2647

    Article  Google Scholar 

  • Khan N, Freeman SD, Virgo P et al (2015) An immunophenotypic pre-treatment predictor for poor response to induction chemotherapy in older acute myeloid leukaemia patients: blood frequency of CD34+ CD38 low blasts. Br J Haematol 170:80–84

    Article  CAS  PubMed  Google Scholar 

  • Kim T, Moon JH, Ahn JS et al (2018) Next-generation sequencing-based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse. Blood 132:1604–1613

    Article  CAS  PubMed  Google Scholar 

  • Klco JM, Miller CA, Griffith M et al (2015) Association between mutation clearance after induction therapy and outcomes in acute myeloid leukemia. JAMA 314:811–822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lambert J, Lambert J, Nibourel O et al (2014) MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin. Oncotarget 5:6280–6288

    Article  PubMed  PubMed Central  Google Scholar 

  • Lancet JE, Uy GL, Cortes JE et al (2018) CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol 36:2684–2692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung W, Pui CH, Coustan-Smith E et al (2012) Detectable minimal residual disease before hematopoietic cell transplantation is prognostic but does not preclude cure for children with very-high-risk leukemia. Blood 120:468–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levine RL, Valk PJM (2019) Next-generation sequencing in the diagnosis and minimal residual disease assessment of acute myeloid leukemia. Haematologica 104:868–871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levis MJ, Perl AE, Altman JK et al (2018) A next-generation sequencing-based assay for minimal residual disease assessment in AML patients with FLT3-ITD mutations. Blood Adv 2:825–831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levis M, Shi W, Chang K et al (2020) FLT3 inhibitors added to induction therapy induce deeper remissions. Blood 135:75–78

    Article  PubMed  Google Scholar 

  • Löwenberg B, Pabst T, Maertens J et al (2021) Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial. Blood Adv 5(4):1110–1121

    Google Scholar 

  • Morita K, Kantarjian HM, Wang F et al (2018) Clearance of somatic mutations at remission and the risk of relapse in acute myeloid leukemia. J Clin Oncol 36:1788–1797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ok CY, Loghavi S, Sui D et al (2019) Persistent IDH1/2 mutations in remission can predict relapse in patients with acute myeloid leukemia. Haematologica 104:305–311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ossenkoppele G, Schuurhuis GJ, van de Loosdrecht A et al (2019) Can we incorporate MRD assessment into clinical practice in AML? Best Pract Res Clin Haematol 32:186–191

    Article  PubMed  Google Scholar 

  • Perl AE, Martinelli G, Cortes JE et al (2019) Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med 381:1728–1740

    Article  CAS  PubMed  Google Scholar 

  • Platzbecker U, Middeke JM, Sockel K et al (2018) Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol 19:1668–1679

    Article  CAS  PubMed  Google Scholar 

  • Platzbecker U, Middeke JM, Sockel K et al (2019) Azacitidine for pre-Emptive treatment of measurable-residual disease in MDS/AML patients at high risk of hematological relapse: results of the second cohort of the RELAZA2 trial. Blood 134(suppl 1):644–644

    Article  Google Scholar 

  • Prassek VV, Rothenberg-Thurley M, Sauerland MC et al (2018) Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged 75 years or older. Haematologica 103:1853–1861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prata PH, Bally C, Prebet T et al (2018) NPM1 mutation is not associated with prolonged complete remission in acute myeloid leukemia patients treated with hypomethylating agents. Haematologica 103:e455–e457

    Article  PubMed  PubMed Central  Google Scholar 

  • Press RD, Eickelberg G, Froman A et al (2019) Next-generation sequencing-defined minimal residual disease before stem cell transplantation predicts acute myeloid leukemia relapse. Am J Hematol 94:902–912

    Article  CAS  PubMed  Google Scholar 

  • Roboz GJ, DiNardo CD, Stein EM et al (2020) Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood 135(7):463–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rucker FG, Agrawal M, Corbacioglu A et al (2019) Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML study group. Blood 134:1608–1618

    Article  PubMed  Google Scholar 

  • Salk JJ, Schmitt MW, Loeb LA (2018) Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations. Nat Rev Genet 19:269–285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santini V, Ossenkoppele GJ (2019) Hypomethylating agents in the treatment of acute myeloid leukemia: a guide to optimal use. Crit Rev Oncol Hematol 140:1–7

    Article  PubMed  Google Scholar 

  • Schlenk RF, Paschka P, Krzykalla J et al (2020) Gemtuzumab ozogamicin in NPM1-mutated acute myeloid leukemia: early results from the prospective randomized AMLSG 09-09 phase III study. J Clin Oncol 38(6):623–632

    Article  CAS  PubMed  Google Scholar 

  • Schuurhuis GJ, Heuser M, Freeman S et al (2018) Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD working party. Blood 131:1275–1291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Short NJ, Rafei H, Daver NG et al (2019) Achievement of complete remission (CR) with measurable residual disease (MRD) negativity is highly prognostic in patients (pts) with relapsed or refractory (R/R) acute myeloid leukemia (AML) receiving first salvage chemotherapy. Blood 134(Suppl 1):735–735

    Article  Google Scholar 

  • Sierra J, Garrido A, Diaz Beya M et al (2019) Final results of the AML12 trial of the Spanish Cetlam Group in Adults with acute myeloid leukemia (AML) up to the age of 70 years: risk adapted post-remission allocation based on genetic data and minimal residual disease. Blood 134:289–289

    Article  Google Scholar 

  • Stein EM, DiNardo CD, Fathi AT et al (2018) Ivosidenib or Enasidenib combined with induction and consolidation chemotherapy in patients with newly diagnosed AML with an IDH1 or IDH2 mutation is safe, effective, and leads to MRD-negative complete remissions. Blood 132(Suppl 1):560–560

    Article  Google Scholar 

  • Stein EM, DiNardo CD, Fathi AT et al (2019) Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib. Blood 133:676–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stone RM, Mandrekar SJ, Sanford BL et al (2017) Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med 377:454–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Terwijn M, van Putten WL, Kelder A et al (2013) 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 31:3889–3897

    Article  PubMed  Google Scholar 

  • Thol F, Gabdoulline R, Liebich A et al (2018) Measurable residual disease monitoring by NGS before allogeneic hematopoietic cell transplantation in AML. Blood 132:1703–1713

    Article  CAS  PubMed  Google Scholar 

  • Thol F, Heida B, Buettner K et al (2019) Post transplantation measurable residual disease (MRD) monitoring using next-generation sequencing is highly predictive for relapse after allogeneic stem cell transplantation. Blood 134(Suppl 1):184–184

    Article  Google Scholar 

  • Tiong IS, Dillon R, Ivey A et al (2019) Rapid elimination of NPM1 mutant measurable residual disease (MRD) using low intensity Venetoclax-based combinations in acute myeloid leukemia (AML). Blood 134(Suppl 1):2648–2648

    Article  Google Scholar 

  • Venditti A, Piciocchi A, Candoni A et al (2019) GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia. Blood 134:935–945

    Article  CAS  PubMed  Google Scholar 

  • Versluis J, Kalin B, Zeijlemaker W et al (2017) Graft-versus-leukemia effect of allogeneic stem-cell transplantation and minimal residual disease in patients with acute myeloid leukemia in first complete remission. JCO Precis Oncol 1:1–13

    PubMed  Google Scholar 

  • Walter RB, Gyurkocza B, Storer BE et al (2015) Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia 29:137–144

    Article  CAS  PubMed  Google Scholar 

  • Wei A, Strickland SA, Hou J-Z et al (2018) Venetoclax with low-dose Cytarabine induces rapid, deep, and durable responses in previously untreated older adults with AML ineligible for intensive chemotherapy. Blood 132(Suppl 1):284–284

    Article  Google Scholar 

  • Wei AH, Döhner H, Pocock C et al (2019a) The QUAZAR AML-001 maintenance trial: results of a phase III international, randomized, double-blind, placebo-controlled study of CC-486 (oral formulation of azacitidine) in patients with acute myeloid leukemia (AML) in first remission. Blood 134(Suppl 2):LBA-3

    Article  Google Scholar 

  • Wei AH, Strickland SA Jr, Hou JZ et al (2019b) Venetoclax combined with low-dose Cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol 37:1277–1284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winters AC, Gutman JA, Purev E et al (2019) Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia. Blood Adv 3:2911–2919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yee KWL, Roboz GJ, O’Connell CL et al (2019) Landmark response and survival analyses from 206 AML patients treated with guadecitabine in a phase 2 study demonstrate the importance of adequate treatment duration to maximize response and survival benefit. Survival benefit not restricted to patients with objective response. Blood 134(Suppl 1):3846

    Article  Google Scholar 

  • Zeijlemaker W, Kelder A, Oussoren-Brockhoff YJ et al (2016) A simple one-tube assay for immunophenotypical quantification of leukemic stem cells in acute myeloid leukemia. Leukemia 30:439–446

    Article  CAS  PubMed  Google Scholar 

  • Zeijlemaker W, Grob T, Meijer R et al (2019) CD34(+)CD38(−) leukemic stem cell frequency to predict outcome in acute myeloid leukemia. Leukemia 33:1102–1112

    Article  CAS  PubMed  Google Scholar 

  • Zhu HH, Zhang XH, Qin YZ et al (2013) 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 121:4056–4062

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Hematology, Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy

    Adriano Venditti

  2. Department of Hematology, University Medical Center, Rotterdam, the Netherlands

    Peter J. M. Valk

  3. Haematology, Guy’s and St Thomas’ NHS Foundation Trust, Guy’s Hospital, London, UK

    Nigel H. Russell

  4. Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

    Sylvie D. Freeman

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  1. Adriano Venditti
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  2. Peter J. M. Valk
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  3. Nigel H. Russell
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  4. Sylvie D. Freeman
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Correspondence to Sylvie D. Freeman .

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  1. Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus, Dresden, Germany

    Christoph Röllig

  2. Department of Haematology, Amsterdam University Medical Center location VUMC, Amsterdam, Noord-Holland, The Netherlands

    Gert J. Ossenkoppele

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Venditti, A., Valk, P.J.M., Russell, N.H., Freeman, S.D. (2021). Future Developments: Measurable Residual Disease. In: Röllig, C., Ossenkoppele, G.J. (eds) Acute Myeloid Leukemia . Hematologic Malignancies. Springer, Cham. https://doi.org/10.1007/978-3-030-72676-8_18

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