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UNDERSTANDING
THE IMPACT OF sAML

Understanding sAML is more important than ever due to increasing incidence, extremely poor prognosis, and therapeutic advances providing more hope1,2

Defining subtypes of sAML

sAML is defined as AML with an antecedent hematological disorder, primarily categorized as AML with myelodysplasia-related changes (AML-MRC), or AML that occurs following exposure to cytotoxic therapy, immunosuppressive therapy, and/or radiotherapy (therapy-related AML, or t-AML)3

The incidence of sAML appears to be increasing due to multiple factors1:

  • Increasing survivorship from prior malignancies
  • Increased use of chemotherapy
  • More precise epidemiological documentation

Approximately 1/3 of AML cases are diagnosed as sAML subtypes AML-MRC and t-AML4,5

Overall prognosis for sAML is poor2

Historically, compared to de novo AML, sAML patients have worse clinical outcomes, including1:

  • Lower rates of complete remission
  • Reduced relapse‑free survival
  • Reduced overall survival

Overall survival probability according to AML type2

Overall survival according to AML type

Granfeldt Østgård LS, et al. Epidemiology and clinical significance of secondary and therapy‑related acute myeloid leukemia: a national population‑based cohort study. J Clin Oncol. 2015;33(31):3641-3649. Reprinted with permission. © 2015 American Society of Clinical Oncology. All rights reserved.

AML with myelodysplasia-related changes (AML-MRC)

AML-MRC makes up approximately 25% of all AML cases4,a

Diagnosed secondary AML patient who is ready to beat their disease

WHO 2016 defines AML-MRC as ≥20% blasts in the peripheral blood or bone marrow and ANY of the following6,7:

Previously documented MDS or MDS/MPN
OR
Myelodysplasia-related cytogenetic abnormalitiesb-d
OR
Multilineage dysplasia:
Dysplasia present in ≥50% of cells in at least 2 cell lines, unless an NPM1 mutation or biallelic mutation of CEBPA is present
  1. Incidence is variable based on the definition of AML-MRC used.4
  2. Complex karyotype: 3 or more abnormalities.7
  3. Unbalanced abnormalities: -7/del(7q), del(5q)/t(5q), i(17q)/t(17p), -13/del(13q), del(11q), del(12p)/t(12p), and idic(X)(q13).7
  4. Balanced abnormalities: t(11;16)(q23.3;p13.3), t(3;21) (q26.2;q22.1), t(1;3)(p36.3;q21.2), t(2;11)(p21;q23.3), t(5;12) (q32;p13.2), t(5;7)(q32;q11.2), t(5;17)(q32;p13.2), t(5;10) (q32;q21.2), and t(3;5)(q25.3;q35.1).7

With advancements in treatment, it is crucial to properly identify AML-MRC through testing

Therapy-related AML (t-AML)

t-AML makes up approximately 4% to 10% of AML cases4,5

Cytotoxic therapies associated with development of t‑AML6,8-11,e

Therapy Latency period
Alkylating agents and radiation 4 to 10 years
Topoisomerase II inhibitors 2 to 3 years
Immunosuppressive therapies 3 to 4 years
  1. Antimetabolites, antimicrotubule agents, growth factors, and immunomodulators have also been implicated in t‑AML.8

sAML has a prevalence that matches or exceeds that of other genetic mutations commonly tested for, such as FLT34,5,12,13

NEXT PAGEIdentification & diagnosis

AML=acute myeloid leukemia; MDS=myelodysplastic syndromes; MPN=myeloproliferative neoplasms.

References: 1. Cheung E, Perissinotti AJ, Bixby DL, et al. The leukemia strikes back: a review of pathogenesis and treatment of secondary AML. Ann Hematol. 2019;98(3):541-559. 2. Granfeldt Østgård LS, Medeiros BC, Sengeløv H, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a national population-based cohort study. J Clin Oncol. 2015;33(31):3641-3649. 3. Ossenkoppele G, Montesinos P. Challenges in the diagnosis and treatment of secondary acute myeloid leukemia. Crit Rev Oncol Hematol. 2019;138:6-13. 4. Nagel G, Weber D, Fromm E, et al; German Austrian AML Study Group (AMLSG). Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO). Ann Hematol. 2017;96(12):1993-2003. 5. Leone G, Mele L, Pulsoni A, et al. The incidence of secondary leukemias. Haematologica. 1999;84(10):937-945. 6. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-951. 7. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. 8. Czader M, Orazi A. Therapy-related myeloid neoplasms. Am J Clin Pathol. 2009;132(3):410-425. 9. Bhatia S. Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol. 2013;40(6):666-675. 10. Godley LA, Larson RA. Therapy-related myeloid leukemia. Semin Oncol. 2008;35(4):418-429. 11. Offman J, Opelz G, Doehler B, et al. Defective DNA mismatch repair in acute myeloid leukemia/myelodysplastic syndrome after organ transplantation. Blood. 2004;104(3):822-828. 12. Daver N, Schlenk RF, Russell NH, et al. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33:299-312. 13. Medeiros BC, Fathi AT, DiNardo CD, et al. Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia. 2017;31(2):272-281.