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Treated secondary acute myeloid leukemia: A distinct high-risk subset of AML with adverse prognosis

  • Prajwal Boddu
    ,
  • Hagop M. Kantarjian
    ,
  • Guillermo Garcia-Manero
    ,
  • Farhad Ravandi
    ,
  • Srdan Verstovsek
    ,
  • Elias Jabbour
*Corresponding author for this work
  • University of Texas MD Anderson Cancer Center
Scholary Output:
Contribution to journal
Article
Peer-review

Open access

Abstract

Secondary acute myeloid leukemia (s-AML) includes therapy-related AML and AML evolving from antecedent hematological disorder (AHD). s-AML arising after treating AHD likely represents a prognostically distinct, high-risk disease category. In this study, treated s-AML (ts-AML) was defined by: (1) prior diagnosis of myelodysplasia, myeloproliferative neoplasm, or aplastic anemia and (2) at least 1 therapy for that diagnosis. ts-AML was categorized by age (, or $60 years), and each cohort assessed for response rates and overall survival (OS) on various treatment regimens. Survival outcomes were compared against other high-risk prognostic subsets. Results showed that complete response and 8-week mortality rates were 32% and 27% in the younger, and 24% and 19% in the older age groups, respectively. There was a significant OS difference within s-AML based on prior treatment of AHD (ie, ts-AML vs s-AML with untreated AHD, 4.2 vs 9.2 months; P, .001). Survival in ts-AML was poor across both cohorts (younger and older, 5 and 4.7 months, respectively). In younger AML, survival was significantly inferior in ts-AML when compared with deletion 5/7, TP53, 3q abnormality, and therapy-related AML groups (median, 5 vs 7.9, 7.8, 7.9, and 11.2 months, respectively; P, .01). Additional adverse karyotype within ts-AML was associated with even worse outcomes (OS range, 1.6-2.8 months). ts-AML represents a very high-risk category, even in younger AML patients. s-AML should be further classified to describe ts-AML, an entity less responsive to currently applied treatment approaches. Future AML trial designs should accommodate ts-AML as a distinct subgroup.

Publication Information

Output type

Scholary Output:
Contribution to journal
Article
Peer-review

Original language

English (US)

Pages from-to (Number of pages)

Pages 1312-1323 (12 pages)

Journal (Volume, Issue Number)

Blood Advances (Volume 1, Issue 17)

Publication milestones

  • Published - 07/25/2017

Publication status

Published - 07/25/2017

ISSN

2473-9529

Publication IDs

  • Scopus: 85048810404
  • PubMed: 29296774
  • ORCID: /0000-0002-8636-1071/work/68888189

Publication metrics

Metrics

Fractional count
1
Fractional count
0.06
Fractional count
17
Fractional count
0.94
Fractional count
1
Fractional count
1
SciVal
citations
40
Scopus
citations
SciVal
FWCI
2.50
SciVal
Author count
18
SciVal
Paper percentile
96
SciVal
Top percentile
5

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88
Citation count
102

Funding Details

In conclusion, poor outcomes in ts-AML are a combined translation of low response rates, high early mortality, and higher risk of early disease relapse. Future investigational treatment approaches including multidrug modulators, antibody-drug conjugates, and molecularly targeted inhibitors should be considered in treating these patients. Although data on an increasing number of effective novel combinations in high-risk AML is emerging in trials, there is an urgent need to evaluate their efficacy in this subset. We propose that the definition of s-AML should be narrowed to define ts-AML, a category of AML typically less responsive to currently applied treatment approaches. Acknowledgments This work was supported in part by the National Institutes of Health, National Cancer Institute (grant CA016672 to the MD Anderson Cancer Center and grant P01 CA049639).
FundersFunding numbers
NIH
-
NCI
P30CA016672
MD Anderson Cancer Center
P01 CA049639