TY - JOUR
T1 - Treated secondary acute myeloid leukemia
T2 - A distinct high-risk subset of AML with adverse prognosis
AU - Boddu, Prajwal
AU - Kantarjian, Hagop M.
AU - Garcia-Manero, Guillermo
AU - Ravandi, Farhad
AU - Verstovsek, Srdan
AU - Jabbour, Elias
AU - Borthakur, Gautam
AU - Konopleva, Marina
AU - Bhalla, Kapil N.
AU - Daver, Naval
AU - DiNardo, Courtney D.
AU - Benton, Christopher B.
AU - Takahashi, Koichi
AU - Estrov, Zeev
AU - Pierce, Sherry R.
AU - Andreeff, Michael
AU - Cortes, Jorge E.
AU - Kadia, Tapan M.
N1 - Funding Information:
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).
Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/7/25
Y1 - 2017/7/25
N2 - 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.
AB - 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.
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U2 - 10.1182/bloodadvances.2017008227
DO - 10.1182/bloodadvances.2017008227
M3 - Article
C2 - 29296774
AN - SCOPUS:85048810404
SN - 2473-9529
VL - 1
SP - 1312
EP - 1323
JO - Blood Advances
JF - Blood Advances
IS - 17
ER -