Minimal Residual Disease in Acute Myeloid Leukemia—Current Status and Future Perspectives

Current Hematologic Malignancy Reports

Volumn 10, Issue 2, 2015, Pages 132-144

  Kayser, Sabine ^a   Walter, Roland B ^b,c   Stock, Wendy ^d   Schlenk, Richard F ^e  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b USA   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

^d UNIVERSITY OF CHICAGO MEDICAL CENTER   (United States)

^e UNIVERSITY HOSPITAL ULM   (Germany)

Author keywords

Acute myeloid leukemia; Minimal residual disease; Multiparameter flow cytometry; Next generation sequencing; Prognostic and predictive value of MRD; Real time quantitative polymerase chain reaction

Indexed keywords

ABELSON KINASE; ANTHRACYCLINE; ANTINEOPLASTIC AGENT; CD135 ANTIGEN; DNA METHYLTRANSFERASE 3A; NUCLEOPHOSMIN; PROTEIN; RUNX1T1 PROTEIN; TRANSCRIPTION FACTOR RUNX1; UNCLASSIFIED DRUG; WT1 PROTEIN; TUMOR MARKER;

ACUTE MYELOBLASTIC LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; FLOW CYTOMETRY; FRAMESHIFT MUTATION; GENE EXPRESSION; HEMATOPOIETIC STEM CELL TRANSPLANTATION; IMMUNOPHENOTYPING; LEUKEMIA REMISSION; LEUKOCYTE; MINIMAL RESIDUAL DISEASE; MOLECULAR PATHOLOGY; MYELOABLATIVE CONDITIONING; NONMYELOABLATIVE CONDITIONING; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; DNA MUTATIONAL ANALYSIS; GENETICS; HIGH THROUGHPUT SEQUENCING; HUMAN; LEUKEMIA, MYELOID, ACUTE; METABOLISM; NEOPLASM, RESIDUAL; PATHOLOGY; PREDICTIVE VALUE; PROCEDURES; PROGNOSIS; REAL TIME POLYMERASE CHAIN REACTION; REMISSION;

BIOMARKERS, TUMOR; DNA MUTATIONAL ANALYSIS; FLOW CYTOMETRY; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; LEUKEMIA, MYELOID, ACUTE; NEOPLASM, RESIDUAL; PREDICTIVE VALUE OF TESTS; PROGNOSIS; REAL-TIME POLYMERASE CHAIN REACTION; REMISSION INDUCTION;

EID: 84929689031     PISSN: 15588211     EISSN: 1558822X     Source Type: Journal    
DOI: 10.1007/s11899-015-0260-7     Document Type: Review

References (100)

1. Burnett A, Wetzler M, Löwenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011;29(5):487–94.
2. Ferrara F, Schiffer CA. Acute myeloid leukaemia in adults. Lancet. 2013;381(9865):484–95.
3. Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74.
4. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21(24):4642–9.
5. 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.
6. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74.
7. Schlenk RF. Post-remission therapy for acute myeloid leukemia. Haematologica. 2014;99(11):1663–70.
8. Terwijn M, van Putten WL, Kelder A, 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. Results of a large clinical trial evaluating the role of immunophenotyping in MRD monitoring.
9. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–84.
10. Vora A, Goulden N, Wade R, et al. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013;14(3):199–209.
11. Vora A, Goulden N, Mitchell C, et al. Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2014;15(8):809–18.
12. Brüggemann M, Raff T, Kneba M. Has MRD monitoring superseded other prognostic factors in adult ALL? Blood. 2012;120(23):4470–81.
13. Brüggemann M, Raff T, Flohr T, et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006;107(3):1116–23.
14. Buyse M, Molenberghs G, Paoletti X, et al. Statistical evaluation of surrogate endpoints with examples from cancer clinical trials. Biom J. 2015 Feb 12. doi: 10.1002/bimj.201400049. [Epub ahead of print].
15. Walter RB, Buckley SA, Pagel JM, 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.
16. Nolan GP, Roederer M, Chattopadhyay PK. A deep profiler’s guide to cytometry. Trends Immunol. 2012;33(7):323–32.
17. Amir el AD, Davis KL, Tadmor MD, et al. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat Biotechnol. 2013;31(6):545–52.
18. Feller N, van der Velden VH, Brooimans RA, 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, e129.
19. 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):2318–57.
20. Baer MR, Stewart CC, Dodge RK, et al. High frequency of immunophenotypic changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B study 8361). Blood. 2001;97(11):3574–80.
21. Langebrake C, Brinkmann I, Teigler-Schlegel A, et al. Immunophenotypic differences between diagnosis and relapse in childhood AML: implications for MRD monitoring. Cytometry B Clin Cytom. 2005;63(1):1–9.
22. Voskova D, Schoch C, Schnittger S, Hiddemann W, Haferlach T, 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 Clin Cytom. 2004;62(1):25–38.
23. Kubista M, Andrade JM, Bengtsson M, et al. The real-time polymerase chain reaction. Mol Aspects Med. 2006;27(2-3):95–125.
24. 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(5):998–1004.
25. Yin JA, O’Brien MA, Hills RK, et al. Minimal residual disease monitoring by RT-qPCR in core-binding factor AML allows risk-stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial. Blood. 2012;120(14):2826–35.
26. Cilloni D, Renneville A, Hermitte F, et al. 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 LeukemiaNet study. J Clin Oncol. 2009;27(31):5195–201.
27. 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):2474–86.
28. Ostergaard M, Nyvold CG, Jovanovic JV, et al. Development of standardized approaches to reporting of minimal residual disease data using a reporting software package designed within the European LeukemiaNet. Leukemia. 2011;25(7):1168–73. This quality control study reports on a software suitable for efficient handling of qPCR data, generation of MRD reports and harmonization of MRD data.
29. 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):3650–8.
30. Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113(9):1875–91.
31. Santamaría C, Chillón MC, Fernández C, et al. Using quantification of the PML-RARalpha transcript to stratify the risk of relapse in patients with acute promyelocytic leukemia. Haematologica. 2007;92(3):315–22.
32. Grimwade D, Jovanovic JV, Hills RK. Can we say farewell to monitoring minimal residual disease in acute promyelocytic leukaemia? Best Pract Res Clin Haematol. 2014;27(1):53–61.
33. Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111–21.
34. 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):4056–62. The authors evaluated a risk-directed therapy approach based on MRD in t(8;21)(q22;q22) AML patients.
35. Jourdan E, Boissel N, Chevret S, et al. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood. 2013;121(12):2213–23. Results of a prospective MRD clinical study in core-binding leukemia.
36. Hoyos M, Nomdedeu JF, Esteve J, et al. Core binding factor acute myeloid leukemia: the impact of age, leukocyte count, molecular findings, and minimal residual disease. Eur J Haematol. 2013;91(3):209–18.
37. Leroy H, de Botton S, Grardel-Duflos N, et al. Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21). Leukemia. 2005;19(3):367–72.
38. Weisser M, Haferlach C, Hiddemann W, Schnittger S. The quality of molecular response to chemotherapy is predictive for the outcome of AML1-ETO-positive AML and is independent of pretreatment risk factors. Leukemia. 2007;21(6):1177–82.
39. Schlenk RF, Benner A, Krauter J, et al. Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol. 2004;22(18):3741–50.
40. Nguyen S, Leblanc T, Fenaux P, et al. A white blood cell index as the main prognostic factor in t(8;21) acute myeloid leukemia (AML): a survey of 161 cases from the French AML Intergroup. Blood. 2002;99(10):3517–23.
41. Schoch C, Haase D, Haferlach T, et al. Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor. Leukemia. 1996;10(8):1288–95.
42. Schnittger S, Kohl TM, Haferlach T, et al. KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood. 2006;107(5):1791–9.
43. Cairoli R, Beghini A, Grillo G, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood. 2006;107(9):3463–8.
44. Boissel N, Leroy H, Brethon B, et al. Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia. 2006;20(6):965–70.
45. Paschka P, Marcucci G, Ruppert AS, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol. 2006;24(24):3904–11.
46. Allen C, Hills RK, Lamb K, et al. The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia. Leukemia. 2013;27(9):1891–901.
47. Prebet T, Bertoli S, Delaunay J, et al. Anthracycline dose intensification improves molecular response and outcome of patients treated for core binding factor acute myeloid leukemia. Haematologica. 2014;99:e185–7.
48. 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):3724–9.
49. Schnittger S, Weisser M, Schoch C, Hiddemann W, Haferlach T, Kern W. New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFBMYH11+ acute myeloid leukemia based on quantification of fusion transcripts. Blood. 2003;102(8):2746–55.
50. Krauter J, Görlich K, Ottmann O, et al. Prognostic value of minimal residual disease quantification by real-time reverse transcriptase polymerase chain reaction in patients with core binding factor leukemias. J Clin Oncol. 2003;21(23):4413–22.
51. Forestier E, Heim S, Blennow E, et al. Cytogenetic abnormalities in childhood acute myeloid leukaemia: a Nordic series comprising all children enrolled in the NOPHO-93-AML trial between 1993 and 2001. Br J Haematol. 2003;121(4):566–77.
52. Byrd JC, Mrózek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100(13):4325–36.
53. Krauter J, Wagner K, Schäfer I, et al. Prognostic factors in adult patients up to 60 years old with acute myeloid leukemia and translocations of chromosome band 11q23: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol. 2009;27(18):3000–6.
54. Scholl C, Breitinger H, Schlenk RF, et al. 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):274–80.
55. Scholl C, Schlenk RF, Eiwen K, et al. The prognostic value of MLL-AF9 detection in patients with t(9;11)(p22;q23)-positive acute myeloid leukemia. Haematologica. 2005;90(12):1626–34.
56. Abildgaard L, Ommen HB, Lausen B, Hasle H, Nyvold CG. A novel RT-qPCR assay for quantification of the MLL-MLLT3 fusion transcript in acute myeloid leukaemia. Eur J Haematol. 2013;91(5):394–8.
57. Falini B, Sportoletti P, Martelli MP. Acute myeloid leukemia with mutated NPM1: diagnosis, prognosis and therapeutic perspectives. Curr Opin Oncol. 2009;21(6):573–81.
58. 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(6):1103–8.
59. 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):2220–31.
60. Krönke J, Bullinger L, Teleanu V, et al. Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia. Blood. 2013;122(1):100–8.
61. 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):2709–16.
62. Hubmann M, Köhnke T, Hoster E, et al. Molecular response assessment by quantitative real-time polymerase chain reaction after induction therapy in NPM1-mutated patients identifies those at high risk of relapse. Haematologica. 2014;99(8):1317–25.
63. Lambert J, Lambert J, Nibourel O, et al. MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin. Oncotarget. 2014;5(15):628–6288. This is one of the first zandomized studies indicating that MRD-assessment may serve as a surrogate for survival endpoints for the treatment under investigation.
64. Shayegi N, Kramer M, Bornhäuser M, et al. 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.
65. Kayser S, Levis MJ. FLT3 tyrosine kinase inhibitors in acute myeloid leukemia: clinical implications and limitations. Leuk Lymphoma. 2014;55(2):243–55.
66. Schnittger S, Schoch C, Kern W, Hiddemann W, Haferlach T. FLT3 length mutations as marker for follow-up studies in acute myeloid leukaemia. Acta Haematol. 2004;112(1-2):68–78.
67. Palmisano M, Grafone T, Ottaviani E, et al. NPM1 mutations are more stable than FLT3 mutations during the course of disease in patients with acute myeloid leukemia. Haematologica. 2007;92(9):1268–9.
68. 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(7):2387–92.
69. Kottaridis PD, Gale RE, Langabeer SE, et al. Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors. Blood. 2002;100(7):2393–8.
70. 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):1217–20.
71. Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Hematology Am Soc Hematol Educ Program. 2013;2013:220–6.
72. Schiller J, Praulich I, Krings Rocha C, Kreuzer KA. Patient-specific analysis of FLT3 internal tandem duplications for the prognostication and monitoring of acute myeloid leukemia. Eur J Haematol. 2012;89(1):53–62.
73. Grunwald MR, Tseng LH, Lin MT, et al. Improved FLT3 internal tandem duplication PCR assay predicts outcome after allogeneic transplant for acute myeloid leukemia. Biol Blood Marrow Transplant. 2014;20(12):1989–95.
74. Lin MT, Tseng LH, Beierl K, et al. Tandem duplication PCR: an ultrasensitive assay for the detection of internal tandem duplications of the FLT3 gene. Diagn Mol Pathol. 2013;22(3):149–55.
75. Thol F, Kölking B, Damm F, et al. Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations. Genes, Chromosomes Cancer. 2012;51(7):689–95.
76. Mardis ER. The $1,000 genome, the $100,000 analysis? Genome Med. 2010;2:84.
77. Ley T, Ding L, Walter M, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424–33.
78. Yan XJ, Xu J, Gu ZH, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet. 2011;43(4):309–15.
79. Shlush LI, Zandi S, Mitchell A, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506(7488):328–33. Identification of the very first mutation in the process of leukemia development.
80. Jaiswal S, Fontanillas P, Flannick J, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371(26):2488–98.
81. Genovese G, Kähler AK, Handsaker RE, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014;371(26):2477–87.
82. Gaidzik VI, Schlenk RF, Paschka P, et al. Clinical impact of DNMT3A mutations in younger adult patients with acute myeloid leukemia: results of the AML Study Group (AMLSG). Blood. 2013;121(23):4769–77.
83. Marcucci G, Metzeler KH, Schwind S, et al. Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol. 2012;30(7):742–50.
84. Hou HA, Kuo YY, Liu CY, et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood. 2012;119(2):559–68.
85. Pløen GG, Nederby L, Guldberg P, et al. Persistence of DNMT3A mutations at long-term remission in adult patients with AML. Br J Haematol. 2014;167(4):478–86.
86. Lasa A, Carricondo M, Estivill C, et al. WT1 monitoring in core binding factor AML: comparison with specific chimeric products. Leuk Res. 2009;33(12):1643–9.
87. Cilloni D, Gottardi E, Fava M, et al. Usefulness of quantitative assessment of the WT1 gene transcript as a marker for minimal residual disease detection. Blood. 2003;102(2):773–4.
88. Cilloni D, Messa F, Arruga F, et al. Early prediction of treatment outcome in acute myeloid leukemia by measurement of WT1 transcript levels in peripheral blood samples collected after chemotherapy. Haematologica. 2008;93(6):921–4.
89. Nowakowska-Kopera A, Sacha T, Florek I, Zawada M, Czekalska S, Skotnicki AB. Wilms’ tumor gene 1 expression analysis by real-time quantitative polymerase chain reaction for monitoring of minimal residual disease in acute leukemia. Leuk Lymphoma. 2009;50(8):1326–32.
90. Rubnitz JE, Inaba H, Dahl G, et al. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial. Lancet Oncol. 2010;11(6):543–52.
91. Sockel K, Wermke M, Radke J, et al. Minimal residual disease-directed preemptive treatment with azacitidine in patients with NPM1-mutant acute myeloid leukemia and molecular relapse. Haematologica. 2011;96(10):1568–70.
92. Greiner J, Ono Y, Hofmann S, et al. Mutated regions of nucleophosmin 1 elicit both CD4(+) and CD8(+) T-cell responses in patients with acute myeloid leukemia. Blood. 2012;120(6):1282–9.
93. Hofmann S, Götz M, Schneider V, et al. Donor lymphocyte infusion induces polyspecific CD8(+) T-cell responses with concurrent molecular remission in acute myeloid leukemia with NPM1 mutation. J Clin Oncol. 2013;31(3):e44–7.
94. Bastos-Oreiro M, Perez-Corral A, Martínez-Laperche C, et al. Prognostic impact of minimal residual disease analysis by flow cytometry in patients with acute myeloid leukemia before and after allogeneic hemopoietic stem cell transplantation. Eur J Haematol. 2014;93(3):239–46.
95. Leung W, Pui CH, Coustan-Smith E, et al. Detectable minimal residual disease before hematopoietic cell transplantation is prognostic but does not preclude cure for children with very-high-risk leukemia. Blood. 2012;120(2):468–72.
96. Wheatley K, Burnett AK, Goldstone AH, et al. A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial United Kingdom Medical Research Council’s Adult and Childhood Leukaemia Working Parties. Brit J Haematol. 1999;107(1):69–79.
97. Kern W, Haferlach T, Schoch C, et al. 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(1):64–70.
98. Freeman SD, Virgo P, Couzens S, 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.
99. San Miguel JF, Vidriales MB, López-Berges C, et al. 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;98:1746–51.
100. Burnett AK, Russell NH, Hills RK, et al. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial. J Clin Oncol. 2013;31(27):3360–8.