General AML

Treated secondary AML is a distinct high-risk subset with adverse prognosis

On 25th July 2017, in an article published in Blood Advances, Prajwal Boddu and colleagues from The University of Texas MD Anderson Cancer Center (MDACC), Houston, Texas, reported results from their retrospective study which aimed to further refine the prognosis of Secondary Acute Myeloid Leukemia (sAML) arising from Antecedent Hematological Disorder (AHD). In particular, they reported on the outcomes of patients who developed AML as a result of a previously treated secondary AHD (ts-AML).

In total, 2,912 newly diagnosed AML patients who were treated at the MDACC between January 2000–December 2015 were retrospectively analyzed in this study. Of these 2,912 patients, 254 (9%) were designated ts-AML and 2,658 patients were designated as a non-ts-AML population.

Patients were further stratified into two study groups including younger patients who were < 60 years (n = 1,160 [ts-AML, n = 51, median age = 52 years]) and older patients who were > 60 years (n = 1,752 [ts-AML, n = 202, median age = 71 years]).

The key results in evaluable patients in the younger ts-AML cohort were:
  • Complete Remission (CR)/CR without platelet recovery (CRp) rate in patients (n = 47); 32%
  • 8-week mortality rate; 27%
  • Overall Survival (OS) in ts-AML (n = 51) and non-ts-AML (n = 1,109) patients in the younger cohort; 5 vs 24 months, P < 0.001  
The key results in evaluable patients in the older ts-AML cohort were:
  • CR/CRp rate in patients (n = 176); 24%
  • 8-week mortality rate; 22%
  • OS in ts-AML (n = 200) and non-ts-AML (n = 1,547) patients in the older cohort; 4.7 vs 9.1 months, P < 0.001  

In summary, “poor outcomes in ts-AML are a combined translation of low response rates, high early mortality, and higher risk of early disease relapse”. Additionally, the outcomes of ts-AML patients were “uniformly dismal regardless of age”.

The authors concluded by proposing that “s-AML should be narrowed to define ts-AML, a category of AML typically less responsive to currently applied treatment approaches”.

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.

References
  1. Boddu P. et al., Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis. Blood Advances. 2017 Jul 25; 1: 1312–1323. DOI: 10.1182/bloodadvances.2017008227.