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Word Count: N/A Main Text Word Count: 339 Number of References: 3 # Correspondence: Josehp D. Khoury, MD Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston, Texas 77030 Phone: 713-745-2387 Fax: 713-794-1800 Email: [email protected] This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/ajh.24862 This article is protected by copyright. All rights reserved. Letter to the Editor Wang and colleagues, in their review of pure erythroid leukemia (PEL), state that “PEL often evolves from prior MDS, but can also develop de novo”. It should be noted that, in the WHO classification, cases evolving from MDS are classified as ‘acute myeloid leukemia with myelodysplasia-related changes’. It would be useful if authors presenting data on PEL could specify if cases met the WHO criteria so that knowledge of this rare subtype of acute myeloid leukemia is increased. Wang et al. report that 10/10 cases studied by them had a TP53 mutation. This raises the question of how many of those patients had de novo disease and thus met the WHO criteria. Response to Dr. Bain’s comment: We appreciate Dr. Bain’s comments on our recent review article on pure erythroid leukemia (PEL)[1]. With regards to the point that PEL cases evolving from MDS should be classified as “acute myeloid leukemia with myelodysplasia-related changes (AML-MRC)”, it should be noted that a prerequisite criterion for AML-MRC in the WHO classification is the presence of 20% or more blasts in peripheral blood or bone marrow. By definition, PEL has >80% immature erythroid precursors, typically with only a minor component of myeloblast that is often well below the required cutoff for AML-MRC. The latter feature was incorporated in the 2016 revision of the WHO classification [2]. Some may argue that proerythroblasts may be counted as blasts; however, if that were the case then all PEL, with or without antecedent MDS, would have to be called AML-MRC since the WHO classification calls for including under AML-MRC all AML with a complex karyotype, a salient feature seen in nearly all PEL[3]. Calling all PEL cases as AML-MRC will eliminate PEL as a distinct category and mitigates increased knowledge of this rare subtype. Indeed, PEL highlights some of the inherent limitations of the AML-MRC category, which is based to a large extent on “consensus” criteria that are mostly not evidence-based (e.g. number of lineages with dysplasic changes, proportion of cells with dysplastic changes in a given lineage, blast percentage cutoff, cytogenetic abnormalities regarded as “sufficient” for calling AML-MRC). With regards to the TP53 mutation data reported in our article, 6 patients presented with de novo disease, 3 had antecedent MDS, and 1 had therapy-related disease. We would underscore that PEL presenting de novo, following MDS or cytotoxic therapy, has the same distinctive morphologic, cytogenetic, and molecular features and is equally associated with a dismal outcome. In summary, the authors contend that WHO classification criteria for AML-MRC are not applicable to PEL and, as such, the diagnosis of PEL should be applied regardless of whether or not a history of antecedent hematologic malignancy or exposure to cytotoxic therapy exists. Wei Wang, MD