1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Medicine
  4. Volume 67, 2016
  5. Article

Annual Review of Medicine

Volume 67, 2016

Diagnosis and Therapy of Acute Myeloid Leukemia in the Era of Molecular Risk Stratification

Abstract

The diagnosis and risk stratification of acute myeloid leukemia (AML) primarily rely on morphologic analysis and assessment of karyotype by chromosome banding analysis. For decades, standard AML induction therapy has utilized the combination of anthracyclines and cytarabine. Despite the use of postremission therapy, less than half of patients with AML will be cured of their disease. Allogeneic hematopoietic stem cell transplantation combines cytoreductive chemotherapy with adoptive immunotherapy and may cure patients who fail chemotherapy alone. Recent advances in next-generation sequencing have yielded important insights into the molecular landscape of AML with normal karyotype. Integrated prognostic models incorporating somatic mutation analyses may outperform prediction based on conventional clinical and cytogenetic factors alone. We review the evolution of risk profiling of AML from the cytogenetic to molecular era and describe the implications for AML diagnosis and postremission therapy.

Keyword(s): allogeneic hematopoietic stem cell transplantation, graft-versus-leukemia, induction chemotherapy, next-generation sequencing, postremission therapy, somatic mutation profiling
Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-051914-021329
2016-01-14
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/med/67/1/annurev-med-051914-021329.html?itemId=/content/journals/10.1146/annurev-med-051914-021329&mimeType=html&fmt=ahah

Literature Cited

  1. Cullen P. 1.  1811. Case of splenitus acutus, in which the serum of the blood drawn from the arm had the appearance of milk. Edinb. Med. Surg. J. 7:169–71 [Google Scholar]
  2. Velpeau A. 2.  1825. Altération du sang. Arch. Gén. Med.462–63
  3. Virchow R. 3.  1845. Weisses Blut. Frorieps Notizen. 36:151–56 [Google Scholar]
  4. Kampen KR. 4.  2012. The discovery and early understanding of leukemia. Leuk. Res. 36:6–13 [Google Scholar]
  5. Mukherjee S. 5.  2010. The Emperor of All Maladies: A Biography of Cancer New York: Scribner
  6. Cassileth PA, Harrington DP, Hines JD. 6.  et al. 1988. Maintenance chemotherapy prolongs remission duration in adult acute nonlymphocytic leukemia. J. Clin. Oncol. 6:583–87 [Google Scholar]
  7. Champlin R, Jacobs A, Gale RP. 7.  et al. 1984. Prolonged survival in acute myelogenous leukaemia without maintenance chemotherapy. Lancet 323:894–96 [Google Scholar]
  8. Cassileth PA, Lynch E, Hines JD. 8.  et al. 1992. Varying intensity of postremission therapy in acute myeloid leukemia. Blood 79:1924–30 [Google Scholar]
  9. Mayer RJ, Davis RB, Schiffer CA. 9.  et al. 1994. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N. Engl. J. Med. 331:896–903 [Google Scholar]
  10. Cassileth PA, Harrington DP, Appelbaum FR. 10.  et al. 1998. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N. Engl. J. Med. 339:1649–56 [Google Scholar]
  11. Schiller G, Gajewski J, Territo M. 11.  et al. 1992. Long-term outcome of high-dose cytarabine-based consolidation chemotherapy for adults with acute myelogenous leukemia. Blood 80:2977–82 [Google Scholar]
  12. Schiller G, Gajewski J, Nimer S. 12.  et al. 1992. A randomized study of intermediate versus conventional-dose cytarabine as intensive induction for acute myelogenous leukaemia. Br. J. Haematol. 81:170–77 [Google Scholar]
  13. Fernandez HF, Sun Z, Yao X. 13.  et al. 2009. Anthracycline dose intensification in acute myeloid leukemia. N. Engl. J. Med. 361:1249–59 [Google Scholar]
  14. Appelbaum FR. 14.  2007. Hematopoietic-cell transplantation at 50. N. Engl. J. Med. 357:1472–75 [Google Scholar]
  15. Gale RP, Champlin RE. 15.  1984. How does bone-marrow transplantation cure leukaemia?. Lancet 324:28–30 [Google Scholar]
  16. Barnes DW, Corp MJ, Loutit JF, Neal FE. 16.  1956. Treatment of murine leukaemia with X rays and homologous bone marrow; preliminary communication. BMJ 2:626–27 [Google Scholar]
  17. Miller JFAP, Mitchell GF. 17.  1968. Cell to cell interaction in the immune response: I. Hemolysin-forming cells in neonatally thymectomized mice reconstituted with thymus or thoracic duct lymphocytes. J. Exp. Med. 128:801–20 [Google Scholar]
  18. Mitchell GF, Miller JFAP. 18.  1968. Cell to cell interaction in the immune response: II. The source of hemolysin-forming cells in irradiated mice given bone marrow and thymus or thoracic duct lymphocytes. J. Exp. Med. 128:821–37 [Google Scholar]
  19. Van Epps HL. 19.  2005. Discovering lymphocyte subsets. J. Exp. Med. 201:5 [Google Scholar]
  20. Thomas ED, Lochte HL, Lu WC, Ferrebee JW. 20.  1957. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N. Engl. J. Med. 257:491–96 [Google Scholar]
  21. Horowitz MM, Gale RP, Sondel PM. 21.  et al. 1990. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75:555–62 [Google Scholar]
  22. Collins RH, Shpilberg O, Drobyski WR. 22.  et al. 1997. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J. Clin. Oncol. 15:433–44 [Google Scholar]
  23. Giralt S, Thall PF, Khouri I. 23.  et al. 2001. Melphalan and purine analog–containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 97:631–37 [Google Scholar]
  24. de Lima M, Anagnostopoulos A, Munsell M. 24.  et al. 2004. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 104:865–72 [Google Scholar]
  25. Rowley JD. 25.  2008. Chromosomal translocations: revisited yet again. Blood 112:2183–89 [Google Scholar]
  26. Khouri IF, Saliba RM, Erwin WD. 26.  et al. 2012. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood 119:6373–78 [Google Scholar]
  27. Grimwade D, Walker H, Oliver F. 27.  et al. 1998. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. Blood 92:2322–33 [Google Scholar]
  28. Berger R, Bernheim A, Ochoa-Noguera ME. 28.  et al. 1987. Prognostic significance of chromosomal abnormalities in acute nonlymphocytic leukemia: a study of 343 patients. Cancer Genet. Cytogenet. 28:293–99 [Google Scholar]
  29. Keating MJ, Smith TL, Kantarjian H. 29.  et al. 1988. Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome. Leukemia 2:403–12 [Google Scholar]
  30. Byrd JC, Mrozek K, Dodge RK. 30.  et al. 2002. 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 100:4325–36 [Google Scholar]
  31. Slovak ML, Kopecky KJ, Cassileth PA. 31.  et al. 2000. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood 96:4075–83 [Google Scholar]
  32. Fröhling S, Schlenk RF, Kayser S. 32.  et al. 2006. Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood 108:3280–88 [Google Scholar]
  33. Grimwade D, Hills RK, Moorman AV. 33.  et al. 2010. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116:354–65 [Google Scholar]
  34. Koreth J, Schlenk R, Kopecky KJ. 34.  et al. 2009. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA 301:2349–61 [Google Scholar]
  35. Schlenk RF, Dohner K, Krauter J. 35.  et al. 2008. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N. Engl. J. Med. 358:1909–18 [Google Scholar]
  36. Dohner H, Estey EH, Amadori S. 36.  et al. 2010. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115:453–74 [Google Scholar]
  37. Ley TJ, Mardis ER, Ding L. 37.  et al. 2008. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 456:66–72 [Google Scholar]
  38. Patel JP, Gonen M, Figueroa ME. 38.  et al. 2012. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N. Engl. J. Med. 366:1079–89 [Google Scholar]
  39. 39. Cancer Genome Atlas Research Network 2013. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368:2059–74 [Google Scholar]
  40. Fried I, Bodner C, Pichler MM. 40.  et al. 2012. Frequency, onset and clinical impact of somatic DNMT3A mutations in therapy-related and secondary acute myeloid leukemia. Haematologica 97:246–50 [Google Scholar]
  41. de Lima M, Giralt S, Thall PF. 41.  et al. 2010. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer 116:5420–31 [Google Scholar]
  42. Jabbour E, Giralt S, Kantarjian H. 42.  et al. 2009. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer 115:1899–905 [Google Scholar]
  43. Shindo T, Kim TK, Benjamin CL. 43.  et al. 2013. MEK inhibitors selectively suppress alloreactivity and graft-versus-host disease in a memory stage-dependent manner. Blood 121:4617–26 [Google Scholar]
  44. Chan SM, Thomas D, Corces-Zimmerman MR. 44.  et al. 2015. Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia. Nat. Med. 21:178–84 [Google Scholar]
  45. Shih AH, Jiang Y, Meydan C. 45.  et al. 2015. Mutational cooperativity linked to combinatorial epigenetic gain of function in acute myeloid leukemia. Cancer Cell 27:502–15 [Google Scholar]
  46. Bejar R, Lord A, Stevenson K. 46.  et al. 2014. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood 124:2705–12 [Google Scholar]
  47. Illendula A, Pulikkan JA, Zong H. 47.  et al. 2015. A small-molecule inhibitor of the aberrant transcription factor CBFbeta-SMMHC delays leukemia in mice. Science 347:779–84 [Google Scholar]
  48. Schnittger S, Kinkelin U, Schoch C. 48.  et al. 2000. Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML. Leukemia 14:796–804 [Google Scholar]
  49. Borkin D, He S, Miao H. 49.  et al. 2015. Pharmacologic inhibition of the menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell 27:589–602 [Google Scholar]
  50. Xie M, Lu C, Wang J. 50.  et al. 2014. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat. Med. 20:1472–78 [Google Scholar]
  51. Jaiswal S, Fontanillas P, Flannick J. 51.  et al. 2014. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371:2488–98 [Google Scholar]
  52. Genovese G, Kähler AK, Handsaker RE. 52.  et al. 2014. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N. Engl. J. Med. 371:2477–87 [Google Scholar]
  53. Lindsley RC, Mar BG, Mazzola E. 53.  et al. 2015. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 26:1367–76 [Google Scholar]
/content/journals/10.1146/annurev-med-051914-021329
Loading
Diagnosis and Therapy of Acute Myeloid Leukemia in the Era of Molecular Risk Stratification
Annual Review of Medicine 67, 59 (2016); https://doi.org/10.1146/annurev-med-051914-021329
/content/journals/10.1146/annurev-med-051914-021329
/content/journals/10.1146/annurev-med-051914-021329
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error