Acute erythroid leukemia (AEL) is a rare subtype of acute myeloid leukemia (AML) primarily affecting older adults and was previously classified into erythroid/myeloid and pure erythroid subtypes. In this pediatric AEL study, we evaluated morphologic, immunophenotypic, cytogenetic, molecular, and clinical data of 24 (1.2%) cases from all cases undergoing central pathology review in Children's Oncology Group trials AAML0531 and AAML1031. Of 24 cases, 5 had a pure erythroid phenotype, and 19 had an erythroid/myeloid phenotype. NUP98 fusions were highly enriched in patients with AEL, occurring in 7 of 22 cases for which molecular data were available (31.8% vs 6.7% in other AML subtypes). Of 5 cases of pure erythroid leukemias (PELs), 3 had NUP98 fusions, and 4 had complex karyotypes. Erythroid/myeloid leukemias were reclassified by using the 2017 World Health Organization hematopathology classification as: myelodysplastic syndrome (MDS) with excess blasts-1 (n 5 3), MDS with excess blasts-2 (n 5 7), AML (nonerythroid, n 5 5), and unknown MDS/AML (n 5 4); the 5 cases of nonerythroid AML included 1 with an NUP98-NSD1 fusion, 2 with myelodysplasia-related changes, and 1 with a complex karyotype. Three cases of MDS with excess blasts-2 also had NUP98 rearrangements. WT1 mutations were present in 5 of 14 cases, all erythroid/myeloid leukemia. Outcomes assessment revealed statistically poorer overall survival (5-year, 20% 6 36% vs 66% 6 23%; P 5.004) and event-free survival (5-year, 20% 6 36% vs 46% 6 23%; P 5.019) for those with PEL than those with erythroid/myeloid leukemia. Our study supports that AEL is a morphologically and genetically heterogeneous entity that is enriched in NUP98 fusions, with the pure erythroid subtype associated with particularly adverse outcomes.
Bibliographical noteFunding Information:
This research was supported by COG Chairs grant U10CA098543, NCTN Network Group Operations Center grant U10CA180886,
The authors thank Vani Shanker from the Department of Scientific Editing (St. Jude Children's Research Hospital, Memphis, TN), for her thorough reading and editing of the manuscript. They also thank the patients and families for participating in these COG trials. This research was supported by COG Chairs grant U10CA098543, NCTN Network Group Operations Center grant U10CA180886, Statistics and Data Center grant U10CA098413, and NCTN Statistics and Data Center grant U10CA180899 from the National Institutes of Health, National Cancer Institute; St. Baldrick's Foundation; Seattle Children's Hospital Mark Alan Bomgardner Endowment (K.M.C.); and Canada Research Chair in Pediatric Oncology Supportive Care (L.S.).
© 2020 by The American Society of Hematology