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. 2017 Jul 19;1(17):1312-1323.
doi: 10.1182/bloodadvances.2017008227. eCollection 2017 Jul 25.

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

Prajwal Boddu  1 , Hagop M Kantarjian  1 , Guillermo Garcia-Manero  1 , Farhad Ravandi  1 , Srdan Verstovsek  1 , Elias Jabbour  1 , Gautam Borthakur  1 , Marina Konopleva  1 , Kapil N Bhalla  1 , Naval Daver  1 , Courtney D DiNardo  1 , Christopher B Benton  1 , Koichi Takahashi  1 , Zeev Estrov  1 , Sherry R Pierce  1 , Michael Andreeff  1 , Jorge E Cortes  1 , Tapan M Kadia  1
Affiliations

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

Prajwal Boddu et al. Blood Adv. .

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.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Younger AML. OS comparisons between the (A) ts-AML and non–ts-AML population, (B) various prognostic risk groups including ts-AML, (C) ts-AML and t-AML, and (D) ts-AML based on whether patients had undergone transplant. chr, chromosome; SCT, allogeneic stem cell transplant; tot, total.
Figure 2.
Figure 2.
Younger AML cohort. OS with ts-AML based on associated presence of (A) monosomy 5/7 and (B) 3q abnormality.
Figure 3.
Figure 3.
OS within younger ts-AML by different induction regimens. INT, intermediate intensity regimen; INV, low-intensity/investigational regimens; m, months.
Figure 4.
Figure 4.
Older AML. OS comparisons between (A) ts-AML and non–ts-AML population, (B) various prognostic risk groups including ts-AML, (C) ts-AML and t-AML, and (D) ts-AML based on whether patients had undergone transplant.
Figure 5.
Figure 5.
Younger AML cohort OS. ts-AML OS based on associated presence of (A) monosomy 5/7 and (B) 3q abnormality.
Figure 6.
Figure 6.
OS within older ts-AML by different induction regimens.
See this image and copyright information in PMC

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