Clinical and prognostic significance of eosinophilia and inv(16)/t(16;16) in pediatric acute myelomonocytic leukemia (AML-M4)

Pediatr Blood Cancer. 2017 Oct;64(10). doi: 10.1002/pbc.26512. Epub 2017 Mar 30.

Abstract

Background: The cytogenetic aberrations inv(16)(p13.1q22)/t(16;16)(p13.1;q22), frequently detected in acute myelomonocytic leukemia with eosinophilia (FAB type M4eo), are generally considered a prognostically favorable subgroup. M4eo comprises a distinct morphology compared to M4 without eosinophilia (M4eo-) and therefore may be indicative for a different pathogenesis.

Procedures: Morphology and cytogenetic/molecular analyses of a Dutch cohort of pediatric acute myelomonocytic leukemia (AML-M4) patients were performed and studied in order to analyze the association between the presence of eosinophilia morphology (M4eo+), inv(16)/t(16;16) (inv(16)+), clinical features, and outcome.

Results: Of the 119 included patients with available combined morphological and cytogenetic results, 60% had M4eo- without inv(16) (inv(16)-), 10% had M4eo-/inv(16)+, 13% had M4eo+/inv(16)-, and 17% had M4eo+/inv(16)+. M4eo+ was significantly associated with the presence of inv(16)/t(16;16) (P < 0.001). Patients with M4eo+ had no significantly superior outcome compared with patients with M4eo-, whereas patients with inv(16)+ had significantly superior probabilities of event-free survival and probabilities of overall survival compared with patients without inv(16)-. Patients with M4eo+/inv(16)+ had no significantly better outcome than those with M4eo-/inv(16)+.

Conclusion: The prognostically favorable impact of distinct morphology with eosinophilia probably relies on its association with inv(16)/t(16;16). Simultaneous presence of both eosinophilia and inv(16) was not associated with superior outcome in our study. These results may be relevant for risk-group classification and risk-group adapted treatment and underline the importance of accurate cytogenetic analysis.

Keywords: M4eo; acute myelomonocytic leukemia; eosinophilia; inv(16)/t(16;16); pediatric AML.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 16 / genetics*
  • Disease-Free Survival
  • Eosinophilia* / genetics
  • Eosinophilia* / mortality
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / mortality
  • Male
  • Netherlands / epidemiology
  • Registries*
  • Survival Rate