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Annals of Hematology

, Volume 98, Issue 3, pp 541–559 | Cite as

The leukemia strikes back: a review of pathogenesis and treatment of secondary AML

  • Edna Cheung
  • Anthony J. Perissinotti
  • Dale L. Bixby
  • Patrick W. Burke
  • Kristen M. Pettit
  • Lydia L. Benitez
  • Julia Brown
  • Gianni B. Scappaticci
  • Bernard L. MariniEmail author
Review Article

Abstract

Secondary AML is associated with a disproportionately poor prognosis, consistently shown to exhibit inferior response rates, event-free survival, and overall survival in comparison with de novo AML. Secondary AML may arise from the evolution of an antecedent hematologic disorder, or it may arise as a complication of prior cytotoxic chemotherapy or radiation therapy in the case of therapy-related AML. Because of the high frequency of poor-risk cytogenetics and high-risk molecular features, such as alterations in TP53, leukemic clones are often inherently chemoresistant. Standard of care induction had long remained conventional 7 + 3 until its reformulation as CPX-351, recently FDA approved specifically for secondary AML. However, recent data also suggests relatively favorable outcomes with regimens based on high-dose cytarabine or hypomethylating agents. With several investigational agents being studied, the therapeutic landscape becomes even more complex, and the treatment approach involves patient-specific, disease-specific, and therapy-specific considerations.

Keywords

Secondary AML Therapy-related AML AML with myelodysplasia-related changes Liposomal daunorubicin and cytarabine FLAG Hypomethylating agents 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

References

  1. 1.
    Granfeldt Østgård LS, Medeiros BC, Sengeløv H, Nørgaard M, Andersen MK, Dufva IH, Friis LS, Kjeldsen E, Marcher CW, Preiss B, Severinsen M, Nørgaard JM (2015) Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a National Population-Based Cohort Study. J Clin Oncol 33(31):3641–3649.  https://doi.org/10.1200/JCO.2014.60.0890 CrossRefGoogle Scholar
  2. 2.
    Hulegårdh E, Nilsson C, Lazarevic V, Garelius H, Antunovic P, Rangert Derolf Å, Möllgård L, Uggla B, Wennström L, Wahlin A, Höglund M, Juliusson G, Stockelberg D, Lehmann S (2015) Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish acute leukemia registry. Am J Hematol 90(3):208–214.  https://doi.org/10.1002/ajh.23908 CrossRefGoogle Scholar
  3. 3.
    Valentini CG, Fianchi L, Voso MT, Caira M, Leone G, Pagano L (2011) Incidence of acute myeloid leukemia after breast cancer. Mediterr J Hematol Infect Dis 3(1):e2011069.  https://doi.org/10.4084/MJHID.2011.069 CrossRefGoogle Scholar
  4. 4.
    Craig BM, Rollison DE, List AF, Cogle CR (2012) Underreporting of myeloid malignancies by United States cancer registries. Cancer Epidemiol Biomark Prev 21(3):474–481.  https://doi.org/10.1158/1055-9965.EPI-11-1087 CrossRefGoogle Scholar
  5. 5.
    Kayser S, Döhner K, Krauter J et al (2011) The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood 117(7):2137–2145.  https://doi.org/10.1182/blood-2010-08-301713 CrossRefGoogle Scholar
  6. 6.
    Borthakur G, Lin E, Jain N, Estey EE, Cortes JE, O'Brien S, Faderl S, Ravandi F, Pierce S, Kantarjian H (2009) Survival is poorer in patients with secondary core-binding factor acute myelogenous leukemia compared with de novo core-binding factor leukemia. Cancer 115(14):3217–3221.  https://doi.org/10.1002/cncr.24367 CrossRefGoogle Scholar
  7. 7.
    Krug U, Röllig C, Koschmieder A, Heinecke A, Sauerland MC, Schaich M, Thiede C, Kramer M, Braess J, Spiekermann K, Haferlach T, Haferlach C, Koschmieder S, Rohde C, Serve H, Wörmann B, Hiddemann W, Ehninger G, Berdel WE, Büchner T, Müller-Tidow C (2010) Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet 376(9757):2000–2008.  https://doi.org/10.1016/S0140-6736(10)62105-8 CrossRefGoogle Scholar
  8. 8.
    Walter RB, Othus M, Borthakur G, Ravandi F, Cortes JE, Pierce SA, Appelbaum FR, Kantarjian HA, Estey EH (2011) Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol 29(33):4417–4424.  https://doi.org/10.1200/JCO.2011.35.7525 CrossRefGoogle Scholar
  9. 9.
    Smith SM, Le Beau MM, Huo D et al (2003) Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood 102(1):43–52.  https://doi.org/10.1182/blood-2002-11-3343 CrossRefGoogle Scholar
  10. 10.
    Larson RA (2007) Etiology and Management of Therapy-Related Myeloid Leukemia. Hematology 2007(1):453–459.  https://doi.org/10.1182/asheducation-2007.1.453 CrossRefGoogle Scholar
  11. 11.
    Christiansen DH, Andersen MK, Pedersen-Bjergaard J (2001) Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 19(5):1405–1413.  https://doi.org/10.1200/JCO.2001.19.5.1405 CrossRefGoogle Scholar
  12. 12.
    Kayastha N, Wolf SP, Locke SC, Samsa GP, El-Jawahri A, LeBlanc TW (2018) The impact of remission status on patients’ experiences with acute myeloid leukemia (AML): an exploratory analysis of longitudinal patient-reported outcomes data. Support Care Cancer 26(5):1437–1445.  https://doi.org/10.1007/s00520-017-3973-4 Google Scholar
  13. 13.
    Tefferi A, Vardiman JW (2009) Myelodysplastic syndromes. N Engl J Med 361(19):1872–1885.  https://doi.org/10.1056/NEJMra0902908 CrossRefGoogle Scholar
  14. 14.
    Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, Kantarjian H, Kuendgen A, Levis A, Malcovati L, Cazzola M, Cermak J, Fonatsch C, le Beau MM, Slovak ML, Krieger O, Luebbert M, Maciejewski J, Magalhaes SMM, Miyazaki Y, Pfeilstocker M, Sekeres M, Sperr WR, Stauder R, Tauro S, Valent P, Vallespi T, van de Loosdrecht AA, Germing U, Haase D (2012) Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120(12):2454–2465.  https://doi.org/10.1182/blood-2012-03-420489 CrossRefGoogle Scholar
  15. 15.
    Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K, Larson DE, McLellan MD, Dooling D, Abbott R, Fulton R, Magrini V, Schmidt H, Kalicki-Veizer J, O'Laughlin M, Fan X, Grillot M, Witowski S, Heath S, Frater JL, Eades W, Tomasson M, Westervelt P, DiPersio JF, Link DC, Mardis ER, Ley TJ, Wilson RK, Graubert TA (2012) Clonal architecture of secondary acute myeloid leukemia. N Engl J Med 366(12):1090–1098.  https://doi.org/10.1056/NEJMoa1106968 CrossRefGoogle Scholar
  16. 16.
    Shukron O, Vainstein V, Kündgen A, Germing U, Agur Z (2012) Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database. Am J Hematol 87(9):853–860.  https://doi.org/10.1002/ajh.23257 CrossRefGoogle Scholar
  17. 17.
    Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL, Pigneux A, Wetzler M, Stuart RK, Erba HP, Damon LE, Powell BL, Lindeman N, Steensma DP, Wadleigh M, DeAngelo DJ, Neuberg D, Stone RM, Ebert BL (2015) Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 125(9):1367–1376.  https://doi.org/10.1182/blood-2014-11-610543 CrossRefGoogle Scholar
  18. 18.
    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405.  https://doi.org/10.1182/blood-2016-03-643544 CrossRefGoogle Scholar
  19. 19.
    Vardiman J, Hyjek E (2011) World health organization classification, evaluation, and genetics of the myeloproliferative neoplasm variants. Hematol Am Soc Hematol Educ Program 2011(1):250–256.  https://doi.org/10.1182/asheducation-2011.1.250 CrossRefGoogle Scholar
  20. 20.
    Cerquozzi S, Tefferi A (2015) Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J 5(11):e366.  https://doi.org/10.1038/bcj.2015.95 CrossRefGoogle Scholar
  21. 21.
    Aynardi J, Manur R, Hess PR et al (2018) JAK2 V617F-positive acute myeloid leukaemia (AML): a comparison between de novo AML and secondary AML transformed from an underlying myeloproliferative neoplasm. A study from the Bone Marrow Pathology Group. Br J Haematol.  https://doi.org/10.1111/bjh.15276
  22. 22.
    Yoshizato T, Dumitriu B, Hosokawa K, Makishima H, Yoshida K, Townsley D, Sato-Otsubo A, Sato Y, Liu D, Suzuki H, Wu CO, Shiraishi Y, Clemente MJ, Kataoka K, Shiozawa Y, Okuno Y, Chiba K, Tanaka H, Nagata Y, Katagiri T, Kon A, Sanada M, Scheinberg P, Miyano S, Maciejewski JP, Nakao S, Young NS, Ogawa S (2015) Somatic mutations and clonal hematopoiesis in aplastic Anemia. N Engl J Med 373(1):35–47.  https://doi.org/10.1056/NEJMoa1414799 CrossRefGoogle Scholar
  23. 23.
    Mauritzson N, Albin M, Rylander L, Billström R, Ahlgren T, Mikoczy Z, Björk J, Strömberg U, Nilsson PG, Mitelman F, Hagmar L, Johansson B (2002) Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001. Leukemia 16(12):2366–2378.  https://doi.org/10.1038/sj.leu.2402713 CrossRefGoogle Scholar
  24. 24.
    Bhatia S (2013) Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol 40(6):666–675.  https://doi.org/10.1053/j.seminoncol.2013.09.013 CrossRefGoogle Scholar
  25. 25.
    Schoch C, Kern W, Schnittger S, Hiddemann W, Haferlach T (2004) Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML. Leukemia 18(1):120–125.  https://doi.org/10.1038/sj.leu.2403187 CrossRefGoogle Scholar
  26. 26.
    Godley LA, Larson RA (2008) Therapy-related myeloid leukemia. Semin Oncol 35(4):418–429.  https://doi.org/10.1053/j.seminoncol.2008.04.012 CrossRefGoogle Scholar
  27. 27.
    Olney HJ, Mitelman F, Johansson B, Mrózek K, Berger R, Rowley JD (2002) Unique balanced chromosome abnormalities in treatment-related myelodysplastic syndromes and acute myeloid leukemia: report from an international workshop. Genes Chromosom Cancer 33(4):413–423 http://www.ncbi.nlm.nih.gov/pubmed/11921275. Accessed 18 June 2018CrossRefGoogle Scholar
  28. 28.
    Pedersen-Bjergaard J, Andersen MK, Andersen MT, Christiansen DH (2008) Genetics of therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 22(2):240–248.  https://doi.org/10.1038/sj.leu.2405078 CrossRefGoogle Scholar
  29. 29.
    Smith RE, Bryant J, DeCillis A, Anderson S (2003) National Surgical Adjuvant Breast and bowel project experience. Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and bowel project experience. J Clin Oncol 21(7):1195–1204.  https://doi.org/10.1200/JCO.2003.03.114 CrossRefGoogle Scholar
  30. 30.
    Curtis RE, Boice JD, Stovall M et al (1992) Risk of leukemia after chemotherapy and radiation treatment for breast Cancer. N Engl J Med 326(26):1745–1751.  https://doi.org/10.1056/NEJM199206253262605 CrossRefGoogle Scholar
  31. 31.
    Zhang W, Becciolini A, Biggeri A, Pacini P, Muirhead CR (2011) Second malignancies in breast cancer patients following radiotherapy: a study in Florence, Italy. Breast Cancer Res 13(2):R38.  https://doi.org/10.1186/bcr2860 CrossRefGoogle Scholar
  32. 32.
    Borrego-Soto G, Ortiz-López R, Rojas-Martínez A (2015) Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer. Genet Mol Biol 38(4):420–432.  https://doi.org/10.1590/S1415-475738420150019 CrossRefGoogle Scholar
  33. 33.
    Dimopoulos MA, Richardson PG, Brandenburg N, Yu Z, Weber DM, Niesvizky R, Morgan GJ (2012) A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide. Blood 119(12):2764–2767.  https://doi.org/10.1182/blood-2011-08-373514 CrossRefGoogle Scholar
  34. 34.
    Ertz-Archambault N, Kosiorek H, Taylor GE, Kelemen K, Dueck A, Castro J, Marino R, Gauthier S, Finn L, Sproat LZ, Palmer J, Mesa RA, al-Kali A, Foran J, Tibes R (2017) Association of Therapy for autoimmune disease with myelodysplastic syndromes and acute myeloid leukemia. JAMA Oncol 3(7):936.  https://doi.org/10.1001/jamaoncol.2016.6435 CrossRefGoogle Scholar
  35. 35.
    Poynter JN, Richardson M, Roesler M, Blair CK, Hirsch B, Nguyen P, Cioc A, Cerhan JR, Warlick E (2017) Chemical exposures and risk of acute myeloid leukemia and myelodysplastic syndromes in a population-based study. Int J Cancer 140(1):23–33.  https://doi.org/10.1002/ijc.30420 CrossRefGoogle Scholar
  36. 36.
    Bullinger L, Döhner K, Döhner H (2017) Genomics of acute myeloid leukemia diagnosis and pathways. J Clin Oncol 35(9):934–946.  https://doi.org/10.1200/JCO.2016.71.2208 CrossRefGoogle Scholar
  37. 37.
    Cancer Genome Atlas Research Network, Ley TJ, Miller C et al (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 368(22):2059–2074.  https://doi.org/10.1056/NEJMoa1301689 CrossRefGoogle Scholar
  38. 38.
    Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, Ritchey JK, Young MA, Lamprecht T, McLellan MD, McMichael JF, Wallis JW, Lu C, Shen D, Harris CC, Dooling DJ, Fulton RS, Fulton LL, Chen K, Schmidt H, Kalicki-Veizer J, Magrini VJ, Cook L, McGrath SD, Vickery TL, Wendl MC, Heath S, Watson MA, Link DC, Tomasson MH, Shannon WD, Payton JE, Kulkarni S, Westervelt P, Walter MJ, Graubert TA, Mardis ER, Wilson RK, DiPersio JF (2012) Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481(7382):506–510.  https://doi.org/10.1038/nature10738 CrossRefGoogle Scholar
  39. 39.
    Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, Wartman LD, Lamprecht TL, Liu F, Xia J, Kandoth C, Fulton RS, McLellan MD, Dooling DJ, Wallis JW, Chen K, Harris CC, Schmidt HK, Kalicki-Veizer JM, Lu C, Zhang Q, Lin L, O’Laughlin MD, McMichael JF, Delehaunty KD, Fulton LA, Magrini VJ, McGrath SD, Demeter RT, Vickery TL, Hundal J, Cook LL, Swift GW, Reed JP, Alldredge PA, Wylie TN, Walker JR, Watson MA, Heath SE, Shannon WD, Varghese N, Nagarajan R, Payton JE, Baty JD, Kulkarni S, Klco JM, Tomasson MH, Westervelt P, Walter MJ, Graubert TA, DiPersio JF, Ding L, Mardis ER, Wilson RK (2012) The origin and evolution of mutations in acute myeloid leukemia. Cell 150(2):264–278.  https://doi.org/10.1016/j.cell.2012.06.023 CrossRefGoogle Scholar
  40. 40.
    Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, Kennedy JA, Schimmer AD, Schuh AC, Yee KW, McLeod JL, Doedens M, Medeiros JJF, Marke R, Kim HJ, Lee K, McPherson JD, Hudson TJ, Pan-Leukemia Gene Panel Consortium THALT, Brown AMK, Yousif F, Trinh QM, Stein LD, Minden MD, Wang JCY, Dick JE (2014) Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 506(7488):328–333.  https://doi.org/10.1038/nature13038 CrossRefGoogle Scholar
  41. 41.
    Milosevic JD, Puda A, Malcovati L, Berg T, Hofbauer M, Stukalov A, Klampfl T, Harutyunyan AS, Gisslinger H, Gisslinger B, Burjanivova T, Rumi E, Pietra D, Elena C, Vannucchi AM, Doubek M, Dvorakova D, Robesova B, Wieser R, Koller E, Suvajdzic N, Tomin D, Tosic N, Colinge J, Racil Z, Steurer M, Pavlovic S, Cazzola M, Kralovics R (2012) Clinical significance of genetic aberrations in secondary acute myeloid leukemia. Am J Hematol 87(11):1010–1016.  https://doi.org/10.1002/ajh.23309 CrossRefGoogle Scholar
  42. 42.
    Joslin JM, Fernald AA, Tennant TR, Davis EM, Kogan SC, Anastasi J, Crispino JD, le Beau MM (2007) Haploinsufficiency of EGR1, a candidate gene in the del(5q), leads to the development of myeloid disorders. Blood 110(2):719–726.  https://doi.org/10.1182/blood-2007-01-068809 CrossRefGoogle Scholar
  43. 43.
    Rücker FG, Schlenk RF, Bullinger L et al (2012) TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood 119(9):2114–2121.  https://doi.org/10.1182/blood-2011-08-375758 CrossRefGoogle Scholar
  44. 44.
    Wong TN, Ramsingh G, Young AL, Miller CA, Touma W, Welch JS, Lamprecht TL, Shen D, Hundal J, Fulton RS, Heath S, Baty JD, Klco JM, Ding L, Mardis ER, Westervelt P, DiPersio JF, Walter MJ, Graubert TA, Ley TJ, Druley TE, Link DC, Wilson RK (2015) Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature 518(7540):552–555.  https://doi.org/10.1038/nature13968 CrossRefGoogle Scholar
  45. 45.
    Larson RA (2012) Cytogenetics, not just previous therapy, determines the course of therapy-related myeloid neoplasms. J Clin Oncol 30(19):2300–2302.  https://doi.org/10.1200/JCO.2011.41.1215 CrossRefGoogle Scholar
  46. 46.
    Michelis FV, Atenafu EG, Gupta V, Kim DD, Kuruvilla J, Lipton JH, Loach D, Seftel MD, Uhm J, Alam N, Lambie A, McGillis L, Messner HA (2015) Comparable outcomes post allogeneic hematopoietic cell transplant for patients with de novo or secondary acute myeloid leukemia in first remission. Bone Marrow Transplant 50(7):907–913.  https://doi.org/10.1038/bmt.2015.59 CrossRefGoogle Scholar
  47. 47.
    Tang F-F, Huang X-J, Zhang X-H, Chen H, Chen YH, Han W, Chen Y, Wang FR, Wang Y, Wang JZ, Yan CH, Sun YQ, Mo XD, Liu KY, Xu LP (2016) Allogeneic hematopoietic cell transplantation for adult patients with treatment-related acute myeloid leukemia during first remission: comparable to de novo acute myeloid leukemia. Leuk Res 47:8–15.  https://doi.org/10.1016/j.leukres.2016.05.005 CrossRefGoogle Scholar
  48. 48.
    Yates JW, Wallace HJ, Ellison RR, Holland JF Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep 57(4):485–488 http://www.ncbi.nlm.nih.gov/pubmed/4586956. Accessed 28 Jul 2018
  49. 49.
    Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, Kooy MM, Verdonck LF, Beck J, Döhner H, Gratwohl A, Pabst T, Verhoef G (2009) High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 361(13):1235–1248.  https://doi.org/10.1056/NEJMoa0901409 CrossRefGoogle Scholar
  50. 50.
    Boddu P, Kantarjian HM, Garcia-Manero G, Ravandi F, Verstovsek S, Jabbour E, Borthakur G, Konopleva M, Bhalla KN, Daver N, DiNardo CD, Benton CB, Takahashi K, Estrov Z, Pierce SR, Andreeff M, Cortes JE, Kadia TM (2017) Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis. Blood Adv 1(17):1312–1323.  https://doi.org/10.1182/bloodadvances.2017008227 CrossRefGoogle Scholar
  51. 51.
    Lancet JE, Uy GL, Cortes JE et al (2016) Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) AML. J Clin Oncol 34(15):Suppl 7000.  https://doi.org/10.1200/JCO.2016.34.15_SUPPL.7000 CrossRefGoogle Scholar
  52. 52.
    Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS (2009) Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 361(13):1249–1259.  https://doi.org/10.1056/NEJMoa0904544 CrossRefGoogle Scholar
  53. 53.
    Löwenberg B, Pabst T, Vellenga E, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Biemond BJ, Gratwohl A, de Greef GE, Verdonck LF, Schaafsma MR, Gregor M, Theobald M, Schanz U, Maertens J, Ossenkoppele GJ (2011) Cytarabine dose for acute myeloid leukemia. N Engl J Med 364(11):1027–1036.  https://doi.org/10.1056/NEJMoa1010222 CrossRefGoogle Scholar
  54. 54.
    Lee J-H, Joo Y-D, Kim H, Bae SH, Kim MK, Zang DY, Lee JL, Lee GW, Lee JH, Park JH, Kim DY, Lee WS, Ryoo HM, Hyun MS, Kim HJ, Min YJ, Jang YE, Lee KH, for the Cooperative Study Group A for Hematology (2011) A randomized trial comparing standard versus high-dose daunorubicin induction in patients with acute myeloid leukemia. Blood 118(14):3832–3841.  https://doi.org/10.1182/blood-2011-06-361410 CrossRefGoogle Scholar
  55. 55.
    Leith CP, Kopecky KJ, Chen IM et al (1999) Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a southwest oncology group study. Blood 94(3):1086–1099 http://www.ncbi.nlm.nih.gov/pubmed/10419902. Accessed 19 June 2018Google Scholar
  56. 56.
    Tsuji K, Wang Y-H, Takanashi M, Odajima T, Lee GA, Sugimori H, Motoji T (2012) Overexpression of lung resistance-related protein and P-glycoprotein and response to induction chemotherapy in acute myelogenous leukemia. Hematol Rep 4(3):e18.  https://doi.org/10.4081/hr.2012.e18 CrossRefGoogle Scholar
  57. 57.
    Tardi P, Johnstone S, Harasym N, Xie S, Harasym T, Zisman N, Harvie P, Bermudes D, Mayer L (2009) In vivo maintenance of synergistic cytarabine:daunorubicin ratios greatly enhances therapeutic efficacy. Leuk Res 33(1):129–139.  https://doi.org/10.1016/j.leukres.2008.06.028 CrossRefGoogle Scholar
  58. 58.
    Brunetti C, Anelli L, Zagaria A, Specchia G, Albano F (2017) CPX-351 in acute myeloid leukemia: can a new formulation maximize the efficacy of old compounds? Expert Rev Hematol 10(10):853–862.  https://doi.org/10.1080/17474086.2017.1369400 CrossRefGoogle Scholar
  59. 59.
    Feldman EJ, Kolitz JE, Trang JM, Liboiron BD, Swenson CE, Chiarella MT, Mayer LD, Louie AC, Lancet JE (2012) Pharmacokinetics of CPX-351; a nano-scale liposomal fixed molar ratio formulation of cytarabine:daunorubicin, in patients with advanced leukemia. Leuk Res 36(10):1283–1289.  https://doi.org/10.1016/j.leukres.2012.07.006 CrossRefGoogle Scholar
  60. 60.
    Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, Komrokji R, Solomon SR, Kolitz JE, Cooper M, Yeager AM, Louie AC, Feldman EJ (2014) Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood 123(21):3239–3246.  https://doi.org/10.1182/blood-2013-12-540971 CrossRefGoogle Scholar
  61. 61.
    Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC (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:JCO2017776112.  https://doi.org/10.1200/JCO.2017.77.6112 CrossRefGoogle Scholar
  62. 62.
    Boddu PC, Kantarjian HM, Ravandi F, Garcia-Manero G, Verstovsek S, Jabbour EJ, Takahashi K, Bhalla K, Konopleva M, DiNardo CD, Ohanian M, Pemmaraju N, Jain N, Pierce S, Wierda WG, Cortes JE, Kadia TM (2017) Characteristics and outcomes of older patients with secondary acute myeloid leukemia according to treatment approach. Cancer 123(16):3050–3060.  https://doi.org/10.1002/cncr.30704 CrossRefGoogle Scholar
  63. 63.
    Vulaj V, Perissinotti AJ, Uebel JR, Nachar VR, Scappaticci GB, Crouch A, Bixby DL, Burke PW, Maillard I, Talpaz M, Marini BL (2018) The FOSSIL study: FLAG or standard 7+3 induction therapy in secondary acute myeloid leukemia. Leuk Res 70:91–96.  https://doi.org/10.1016/j.leukres.2018.05.011 CrossRefGoogle Scholar
  64. 64.
    Becker PS, Medeiros BC, Stein AS, Othus M, Appelbaum FR, Forman SJ, Scott BL, Hendrie PC, Gardner KM, Pagel JM, Walter RB, Parks C, Wood BL, Abkowitz JL, Estey EH (2015) G-CSF priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm. Am J Hematol 90(4):295–300.  https://doi.org/10.1002/ajh.23927 CrossRefGoogle Scholar
  65. 65.
    Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJM, Muus P, Mistrik M, Amadori S, Specchia G, Fabbiano F, Nobile F, Sborgia M, Camera A, Selleslag DLD, Lefrère F Sr, Magro D, Sica S, Cantore N, Beksac M, Berneman Z, Thomas X, Melillo L, Guimaraes JE, Leoni P, Luppi M, Mitra ME, Bron D, Fillet G, Marijt EWA, Venditti A, Hagemeijer A, Mancini M, Jansen J, Cilloni D, Meert L, Fazi P, Vignetti M, Trisolini SM, Mandelli F, de Witte T (2014) High-dose Cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol 32(3):219–228.  https://doi.org/10.1200/JCO.2013.51.8571 CrossRefGoogle Scholar
  66. 66.
    Godley LA, Njiaju UO, Green M, Weiner H, Lin S, Odenike O, Rich ES, Artz A, van Besien K, Daugherty CK, Zhang Y, le Beau MM, Stock W, Larson RA (2010) Treatment of therapy-related myeloid neoplasms with high-dose cytarabine/mitoxantrone followed by hematopoietic stem cell transplant. Leuk Lymphoma. 51(6):995–1006.  https://doi.org/10.3109/10428191003763468 CrossRefGoogle Scholar
  67. 67.
    DiNardo CD, Pratz K, Pullarkat V et al (2018) Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood.  https://doi.org/10.1182/blood-2018-08-868752
  68. 68.
    Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, de Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F (2016) Gemtuzumab Ozogamicin versus best supportive Care in Older Patients with Newly Diagnosed Acute Myeloid Leukemia Unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol 34(9):972–979.  https://doi.org/10.1200/JCO.2015.64.0060 CrossRefGoogle Scholar
  69. 69.
    Abboud CN, ξ Þ, Altman JK, et al (2018) NCCN Guidelines Version 2.2018 Acute Myeloid Leukemia. https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed 13 Oct 2018
  70. 70.
    Maertens J (2007) Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies. Eur J Haematol 78(4):275–282.  https://doi.org/10.1111/j.1600-0609.2006.00805.x CrossRefGoogle Scholar
  71. 71.
    Cornely OA, Böhme A, Reichert D, Reuter S, Maschmeyer G, Maertens J, Buchheidt D, Paluszewska M, Arenz D, Bethe U, Effelsberg J, Lövenich H, Sieniawski M, Haas A, Einsele H, Eimermacher H, Martino R, Silling G, Hahn M, Wacker S, Ullmann AJ, Karthaus M, Multinational Case Registry of the Infectious Diseases Working Party of the German Society for Hematology and Oncology (2008) Risk factors for breakthrough invasive fungal infection during secondary prophylaxis. J Antimicrob Chemother 61(4):939–946.  https://doi.org/10.1093/jac/dkn027 CrossRefGoogle Scholar
  72. 72.
    Lancet JE, Ritchie EK, Uy GL et al (2017) Efficacy and Safety of CPX-351 Versus 7+3 in Older Adults with Secondary Acute Myeloid Leukemia: Combined Subgroup Analysis of Phase 2 and Phase 3 Studies. Blood 130(Suppl 1) http://www.bloodjournal.org/content/130/Suppl_1/2657?sso-checked=true. Accessed 19 June 2018
  73. 73.
    Lancet JE, Uy GL, Cortes JE, et al (2017) Analysis of Transplantation Rate and Overall Treatment Efficacy By Age for Patients Aged 60 to 75 with Untreated Secondary Acute Myeloid Leukemia (AML) Given CPX-351 Liposome Injection Versus Conventional Cytarabine and Daunorubicin in a Phase III Trial. BMT Tandem Meetings. https://bmt.confex.com/tandem/2017/meetingapp.cgi/Paper/8916. Published 2017. Accessed 19 June 2018
  74. 74.
    Walter RB, Othus M, Orlowski KF, McDaniel EN, Scott BL, Becker PS, Percival MEM, Hendrie PC, Medeiros BC, Chiarella MT, Louie AC, Estey EH (2018) Unsatisfactory efficacy in randomized study of reduced-dose CPX-351 for medically less fit adults with newly diagnosed acute myeloid leukemia or other high-grade myeloid neoplasm. Haematologica 103(3):e106–e109.  https://doi.org/10.3324/haematol.2017.182642 CrossRefGoogle Scholar
  75. 75.
    Assi R, Kantarjian HM, Verstovsek S et al (2016) CPX-351 for the Treatment of High-Risk Patients with Acute Myeloid Leukemia. Blood 128(22) http://www.bloodjournal.org/content/128/22/4047?sso-checked=true. Accessed 19 June 2018
  76. 76.
    Gandhi V, Estey E, Keating MJ, Plunkett W (1993) Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy. J Clin Oncol 11(1):116–124.  https://doi.org/10.1200/JCO.1993.11.1.116 CrossRefGoogle Scholar
  77. 77.
    Bashey A, Liu L, Ihasz A, Medina B, Corringham S, Keese K, Carrier E, Castro JE, Holman P, Lane TA, Hassidim K, Ball ED (2006) Non-anthracycline based remission induction therapy for newly diagnosed patients with acute myeloid leukemia aged 60 or older. Leuk Res 30(4):503–506.  https://doi.org/10.1016/j.leukres.2005.09.002 CrossRefGoogle Scholar
  78. 78.
    Ferrara F, Palmieri S, Izzo T, Criscuolo C, Riccardi C (2010) Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome. Hematol Oncol 28(4):202–208.  https://doi.org/10.1002/hon.943 CrossRefGoogle Scholar
  79. 79.
    Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR (2010) Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 28(4):562–569.  https://doi.org/10.1200/JCO.2009.23.8329 CrossRefGoogle Scholar
  80. 80.
    Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Bernal del Castillo T, al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Dohner H (2015) International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 126(3):291–299.  https://doi.org/10.1182/blood-2015-01-621664 CrossRefGoogle Scholar
  81. 81.
    Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, Gau JP, Chou WC, Buckstein R, Cermak J, Kuo CY, Oriol A, Ravandi F, Faderl S, Delaunay J, Lysák D, Minden M, Arthur C (2012) Multicenter, randomized, open-label, phase III trial of Decitabine versus patient choice, with physician advice, of either supportive care or low-dose Cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 30(21):2670–2677.  https://doi.org/10.1200/JCO.2011.38.9429 CrossRefGoogle Scholar
  82. 82.
    Pleyer L, Stauder R, Burgstaller S, Schreder M, Tinchon C, Pfeilstocker M, Steinkirchner S, Melchardt T, Mitrovic M, Girschikofsky M, Lang A, Krippl P, Sliwa T, Egle A, Linkesch W, Voskova D, Angermann H, Greil R (2013) Azacitidine in patients with WHO-defined AML—results of 155 patients from the Austrian Azacitidine registry of the AGMT-study group. J Hematol Oncol 6(1):32.  https://doi.org/10.1186/1756-8722-6-32 CrossRefGoogle Scholar
  83. 83.
    Dumas P-Y, Bertoli S, Bérard E et al (2017) Azacitidine or intensive chemotherapy for older patients with secondary or therapy-related acute myeloid leukemia. Oncotarget 8(45):79126–79136.  https://doi.org/10.18632/oncotarget.15988 CrossRefGoogle Scholar
  84. 84.
    Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, Wilson RK, Baty JD, Duncavage EJ, Tandon B, Lee YS, Wartman LD, Uy GL, Ghobadi A, Tomasson MH, Pusic I, Romee R, Fehniger TA, Stockerl-Goldstein KE, Vij R, Oh ST, Abboud CN, Cashen AF, Schroeder MA, Jacoby MA, Heath SE, Luber K, Janke MR, Hantel A, Khan N, Sukhanova MJ, Knoebel RW, Stock W, Graubert TA, Walter MJ, Westervelt P, Link DC, DiPersio JF, Ley TJ (2016) TP53 and Decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med 375(21):2023–2036.  https://doi.org/10.1056/NEJMoa1605949 CrossRefGoogle Scholar
  85. 85.
    Ravandi F, Issa J-P, Garcia-Manero G, O'Brien S, Pierce S, Shan J, Borthakur G, Verstovsek S, Faderl S, Cortes J, Kantarjian H (2009) Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities. Cancer 115(24):5746–5751.  https://doi.org/10.1002/cncr.24661 CrossRefGoogle Scholar
  86. 86.
    Bogenberger JM, Delman D, Hansen N, Valdez R, Fauble V, Mesa RA, Tibes R (2015) Ex vivo activity of BCL-2 family inhibitors ABT-199 and ABT-737 combined with 5-azacytidine in myeloid malignancies. Leuk Lymphoma. 56(1):226–229.  https://doi.org/10.3109/10428194.2014.910657 CrossRefGoogle Scholar
  87. 87.
    Maiti A, DiNardo CD, Cortes JE, et al (2018) Interim analysis of phase II study of Venetoclax with 10-day Decitabine (DEC10-VEN) in acute myeloid leukemia and myelodysplastic syndrome. https://ash.confex.com/ash/2018/webprogram/Paper113749.html. Accessed 17 Nov 2018
  88. 88.
    Maurillo L, Buccisano F, Spagnoli A, Voso MT, Fianchi L, Papayannidis C, Gaidano GL, Breccia M, Musto P, de Bellis E, del Principe MI, Lunghi M, Lessi F, Martinelli G, Venditti A (June) Comparative analysis of azacitidine and intensive chemotherapy as front-line treatment of elderly patients with acute myeloid leukemia. Ann Hematol 97:1767–1774.  https://doi.org/10.1007/s00277-018-3374-x
  89. 89.
    Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, Larson RA, Erba HP, Stiff PJ, Stuart RK, Walter RB, Tallman MS, Stenke L, Appelbaum FR (2013) A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood 121(24):4854–4860.  https://doi.org/10.1182/blood-2013-01-466706 CrossRefGoogle Scholar
  90. 90.
    Castaigne S, Pautas C, Terré C et al (2014) Final Analysis of the ALFA 0701 Study. Blood 124(21) http://www.bloodjournal.org/content/124/21/376?sso-checked=true. Accessed 19 June 2018
  91. 91.
    Hills RK, Castaigne S, Appelbaum FR, Delaunay J, Petersdorf S, Othus M, Estey EH, Dombret H, Chevret S, Ifrah N, Cahn JY, Récher C, Chilton L, Moorman AV, Burnett AK (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(9):986–996.  https://doi.org/10.1016/S1470-2045(14)70281-5 CrossRefGoogle Scholar
  92. 92.
    Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JAL, Hunter A, Goldstone AH, Wheatley K (2011) Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol 29(4):369–377.  https://doi.org/10.1200/JCO.2010.31.4310 CrossRefGoogle Scholar
  93. 93.
    Burnett AK, Russell NH, Hills RK, Kell J, Freeman S, Kjeldsen L, Hunter AE, Yin J, Craddock CF, Dufva IH, Wheatley K, Milligan D (2012) Addition of Gemtuzumab Ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol 30(32):3924–3931.  https://doi.org/10.1200/JCO.2012.42.2964 CrossRefGoogle Scholar
  94. 94.
    Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, de Fabritiis P, Venditti A, Ho AD, Lübbert M, Thomas X, Latagliata R, Halkes CJM, Falzetti F, Magro D, Guimaraes JE, Berneman Z, Specchia G, Karrasch M, Fazi P, Vignetti M, Willemze R, de Witte T, Marie JP (2013) Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol 31(35):4424–4430.  https://doi.org/10.1200/JCO.2013.49.0771 CrossRefGoogle Scholar
  95. 95.
    van der Velden VHJ, Boeckx N, Jedema I, te Marvelde JG, Hoogeveen PG, Boogaerts M, van Dongen JJM (2004) High CD33-antigen loads in peripheral blood limit the efficacy of gemtuzumab ozogamicin (Mylotarg) treatment in acute myeloid leukemia patients. Leukemia 18(5):983–988.  https://doi.org/10.1038/sj.leu.2403350 CrossRefGoogle Scholar
  96. 96.
    Dowell JA, Korth-Bradley J, Liu H, King SP, Berger MS (2001) Pharmacokinetics of gemtuzumab ozogamicin, an antibody-targeted chemotherapy agent for the treatment of patients with acute myeloid leukemia in first relapse. J Clin Pharmacol 41(11):1206–1214 http://www.ncbi.nlm.nih.gov/pubmed/11697753. Accessed 19 June 2018CrossRefGoogle Scholar
  97. 97.
    Candoni A, Papayannidis C, Martinelli G, Simeone E, Gottardi M, Iacobucci I, Gherlinzoni F, Visani G, Baccarani M, Fanin R (2018) Flai (fludarabine, cytarabine, idarubicin) plus low-dose Gemtuzumab Ozogamicin as induction therapy in CD33-positive AML: final results and long term outcome of a phase II multicenter clinical trial. Am J Hematol 93(5):655–663.  https://doi.org/10.1002/ajh.25057 CrossRefGoogle Scholar
  98. 98.
    Stein EM, Walter RB, Erba HP, Fathi AT, Advani AS, Lancet JE, Ravandi F, Kovacsovics T, DeAngelo DJ, Bixby D, Faderl S, Jillella AP, Ho PA, O’Meara MM, Zhao B, Biddle-Snead C, Stein AS (2018) A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood 131(4):387–396.  https://doi.org/10.1182/blood-2017-06-789800 CrossRefGoogle Scholar
  99. 99.
    Stone RM, Mazzola E, Neuberg D, Allen SL, Pigneux A, Stuart RK, Wetzler M, Rizzieri D, Erba HP, Damon L, Jang JH, Tallman MS, Warzocha K, Masszi T, Sekeres MA, Egyed M, Horst HA, Selleslag D, Solomon SR, Venugopal P, Lundberg AS, Powell B (2015) Phase III open-label randomized study of Cytarabine in combination with Amonafide L-malate or Daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. J Clin Oncol 33(11):1252–1257.  https://doi.org/10.1200/JCO.2014.57.0952 CrossRefGoogle Scholar
  100. 100.
    Cazzola M (2010) IDH1 and IDH2 mutations in myeloid neoplasms--novel paradigms and clinical implications. Haematologica 95(10):1623–1627.  https://doi.org/10.3324/haematol.2010.030015 CrossRefGoogle Scholar
  101. 101.
    Boddu P, Kantarjian H, Garcia-Manero G, Allison J, Sharma P, Daver N (2018) The emerging role of immune checkpoint based approaches in AML and MDS. Leuk Lymphoma 59(4):790–802.  https://doi.org/10.1080/10428194.2017.1344905 CrossRefGoogle Scholar
  102. 102.
    Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, Fang Z, Nguyen M, Pierce S, Wei Y, Parmar S, Cortes J, Kantarjian H, Garcia-Manero G (2014) Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia 28(6):1280–1288.  https://doi.org/10.1038/leu.2013.355 CrossRefGoogle Scholar
  103. 103.
    Pratz KW, Rudek MA, Gojo I, Litzow MR, McDevitt MA, Ji J, Karnitz LM, Herman JG, Kinders RJ, Smith BD, Gore SD, Carraway HE, Showel MM, Gladstone DE, Levis MJ, Tsai HL, Rosner G, Chen A, Kaufmann SH, Karp JE (2017) A phase I study of Topotecan, carboplatin and the PARP inhibitor Veliparib in acute Leukemias, aggressive myeloproliferative neoplasms, and chronic Myelomonocytic leukemia. Clin Cancer Res 23(4):899–907.  https://doi.org/10.1158/1078-0432.CCR-16-1274 CrossRefGoogle Scholar
  104. 104.
    Zeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE (2015) Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica 100(9):1172–1179.  https://doi.org/10.3324/haematol.2015.125849 CrossRefGoogle Scholar
  105. 105.
    Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Löwenberg B, Bloomfield CD (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447.  https://doi.org/10.1182/blood-2016-08-733196 CrossRefGoogle Scholar
  106. 106.
    (NICE) NI for H and CE (2018) Appraisal Consultation Document-Liposomal Cytarabine and Daunorubicin for Untreated Acute Myeloid Leukaemia Liposomal Cytarabine and Daunorubicin for Untreated Acute Myeloid Leukaemia. https://www.nice.org.uk/guidance/gid-ta10230/documents/appraisal-consultation-document. Accessed 17 Nov 2018
  107. 107.
    Ommen HB (2016) Monitoring minimal residual disease in acute myeloid leukaemia: a review of the current evolving strategies. Ther Adv Hematol 7(1):3–16.  https://doi.org/10.1177/2040620715614529 CrossRefGoogle Scholar
  108. 108.
    Talati C (2018) Comparison of induction strategies and responses for acute myeloid leukemia patients after resistance to Hypomethylating agents for antecedent myeloid malignancy. https://ash.confex.com/ash/2018/webprogram/Paper119879.html. Accessed 10 Dec 2018
  109. 109.
    Cortes JE, Goldberg SL, Feldman EJ, Rizzeri DA, Hogge DE, Larson M, Pigneux A, Recher C, Schiller G, Warzocha K, Kantarjian H, Louie AC, Kolitz JE (2015) Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer 121(2):234–242.  https://doi.org/10.1002/cncr.28974 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Edna Cheung
    • 1
  • Anthony J. Perissinotti
    • 1
  • Dale L. Bixby
    • 2
  • Patrick W. Burke
    • 2
  • Kristen M. Pettit
    • 2
  • Lydia L. Benitez
    • 1
  • Julia Brown
    • 1
  • Gianni B. Scappaticci
    • 1
  • Bernard L. Marini
    • 1
    Email author
  1. 1.Department of Pharmacy Services and Clinical SciencesMichigan Medicine and University of Michigan College of PharmacyAnn ArborUSA
  2. 2.Department of Internal Medicine, Division of Hematology/Oncology, Adult BMT and Leukemia ProgramsMichigan Medicine and University of Michigan Medical SchoolAnn ArborUSA

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