title: Clinical and prognostic significance of eosinophilia and inv(16)/t(16;16) in pediatric acute myelomonocytic leukemia (AML-M4).
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.
  
  
  METHODS
  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)+.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Klein
authors.affiliation: Dutch Childhood Oncology Group, The Hague, The Netherlands.|Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Valérie
authors.initials: V
authors.lastname: de Haas
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ingrid E M
authors.initials: IEM
authors.lastname: Bank
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Center/Dutch Working Group Hemato-oncological Genome Diagnostics, Rotterdam, The Netherlands.
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus University Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: C Michel
authors.initials: CM
authors.lastname: Zwaan
authors.affiliation: Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands.|Dutch Childhood Oncology Group, The Hague, The Netherlands.|Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Gertjan L
authors.initials: GL
authors.lastname: Kaspers
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D018572:Disease-Free Survival; D004802:Eosinophilia / Q000235:genetics / Q000401:mortality; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D012042:Registries; D015996:Survival Rate
keywords: M4eo; acute myelomonocytic leukemia; eosinophilia; inv(16)/t(16;16); pediatric AML