Blood Advances (Jul 2017)

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,
  • Gautam Borthakur,
  • Marina Konopleva,
  • Kapil N. Bhalla,
  • Naval Daver,
  • Courtney D. DiNardo,
  • Christopher B. Benton,
  • Koichi Takahashi,
  • Zeev Estrov,
  • Sherry R. Pierce,
  • Michael Andreeff,
  • Jorge E. Cortes,
  • Tapan M. Kadia

Journal volume & issue
Vol. 1, no. 17
pp. 1312 – 1323

Abstract

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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.