Counting bone marrow blasts as a percentage of nonerythroid cells improves the prognostic evaluation of MDS with erythroid predominance
Authors: Yan Yu, Tongtong Zhang, Qinrong Wang, Depei Wu, Jinlan Pan, Jianying Liang, Suning Chen, Aining Sun
Journal: American Journal of Hematology (2017)

Myelodysplastic syndrome (MDS) with erythroid predominance [≥50% erythroid nucleated cells (ENCs), MDS-erythroid] comprises a significant proportion of MDS cases.1 The 2008 WHO classification recommended enumerating BM blasts from nonerythroid blasts cell (NECs) when bone marrow (BM) erythroblasts were ≥50%. However, the NECs count rule was removed in the 2016 revision of the WHO criteria.2 This decision is a sweeping change that impacts both the acute myeloid leukemia (AML) and MDS categories. Erythroid/myeloid type, a subcategory of acute erythroid leukemia, has been removed from the AML category, and approximately one-third of acute erythroleukemia cases have been reclassified as MDS.3 Additionally, considering that there was no consensus on a more appropriate way of enumerating BM)blasts from total nucleated cells (TNCs) or NECs in MDS-erythroid patients, we retrospectively analyzed a cohort of 1193 MDS patients and 135 acute erythroleukemia patients from a single center in China from January 2010 to December 2015, and simultaneously reclassified these patients according to WHO (2016) criteria. Outcome data were updated as of August 2016 for a median follow-up of 38 months. A total of 346 (27.0%, 346/1283) patients with MDS-erythroid and 937 (73.0%, 937/1283) patients with MDS with <50% ENCs (control group) who fulfilled the WHO (2016) criteria were identified. Two-thirds (90/135) of acute erythroleukemia patients were reclassified as MDS due to BM blast proportions of <20% TNCs, ≥20% NECs, and ≥50% ENCs. These newly categorized MDS patients accounted for 26.0% (90/346) of the MDS-erythroid patients. The rest of the 256 patients (74.0%, 256/346) had ≥50% ENCs and <20% BM blasts. Supporting Information Table S1 summarized the baseline characteristics of all enrolled patients. In all MDS-erythroid patients, the median age at diagnosed was 57 years old (range 13–89 years old), with 61.0% patients older than 50 years. A total of 145 MDS-erythroid patients (41.9%) were observed to have clonal chromosome abnormalities, of which 52 patients possessed a complex karyotype. The most common type of chromosome aberration was trisomy 8 (14.45%, 50/346). Other aberrations, in order of frequency, were −7/del(7q) (9.54%), −20/del(20q) (8.96%), and −5/del(5q) (7.51%). In addition, we compared the clinical and genetic characteristics of MDS-erythroid with MDS possessing <50% ENCs and found that there were no significant differences except for BM blast percentage (by TNCs, median, 3.0% vs. 4.0%; P = .007; by NECs, median, 8.0 vs. 6.0%; P < .001; Supporting Information Table S1). Simultaneously, the overall survival (OS) by univariate analysis between MDS-erythroid patients and MDS patients with <50% ENCs had also no statistical difference (median OS, 40.0 vs. 36.0 months; P > .05, Supporting Information Fig S1A). Similar results were also reported in an additional series of studies.4, 5 By calculating the percentage of BM blasts from NECs, 62.1% (215/346) of patients were re-classified into the higher-risk WHO categories from the initial types calculated from TNCs; 64 of 346 patients (18.5%) were reclassified as MDS with excess blasts (EB) 1 subtype (MDS-EB-1), 61 of 346 patients (17.6%) were reclassified as MDS with EB 2 subtype (MDS-EB-2), and 90 (26.0%) patients were reclassified as AML (Table 1). Following the WHO recommendations, MDS without EB diagnosis was not possible in recorded AML, as patients with <5% BM blasts from TNCs fulfilled the pure erythroleukemia criteria. Therefore, only MDS-EB was reclassified to AML. A total of 215 upgraded patients had poor survival compared to the 131 patients from the unchanged MDS-erythroid group (median OS, 31 months vs. not reached, P = .011). A total of 73 of 200 patients (36.5%) with MDS-erythroid who were diagnosed by WHO subtypes without EB were reclassified into the higher-risk categories—64 patients as MDS-EB-1 and 9 as MDS-EB-2. The OS of these 73 patients was significantly shorter than the 127 patients whose WHO subtypes remained without EB (median OS, 31 months vs. not reached, P = .038, Supporting Information Fig. S1B). We further compared these 73 upgraded patients with 699 MDS patients without EB and with <50% ENCs, and found that the median OS of the reclassified patients was also shorter than the control group (median OS, 31 vs. 48 months, P = .058). We observed that when patients had ≥50% ENCs and 5–20% BM blasts from TNCs, they were shifted to a higher-risk group: 83 MDS-EB-1 were re-classified, 52 to MDS-EB-2 and 31 to AML with ≥20% NECs. In addition, 59 MDS-EB-2 patients were re-classified to AML with ≥20% NECs, and in 4 patients in the MDS-EB-2 group of MDS-erythroid, the BM blasts from TNCs was <10%, but Auer rods were present (Table 1). Furthermore, we also evaluated OS in MDS-erythroid patients using the International Prognostic Scoring System-Revised (IPSS-R) categories by enumerating BM blasts from TNCs (P = .036, Supporting Information Fig. S1C) and from NECs (P = .003, Supporting Information Fig. S1D). A total of 40 of 168 MDS-erythroid patients (23.8%) in relatively low-risk categories (including very low, low and intermediate categories according to IPSS-R) were reclassified to higher-risk categories (including high and very high categories; Supporting Information Table S2). Additionally, these patients had significantly shorter OS than patients who remained in the lower-risk categories (median OS, 34 months vs. not reached; P = .030, Supporting Information Fig. S1E), especially in the intermediate risk group as stratified by IPSS-R (median OS, 22 months for reclassified patients vs. not reached for unchanged patients, P = .007, Supporting Information Fig. S1F). This study analyzed the clinicopathologic features of a large series of patients with primary MDS-erythroid. And we compared two methods (enumeration of BM blasts from TNCs and from NECs) in disease classification and risk stratification to calculate the percentage of BM blasts for MDS-erythroid. Our study highlighted the prognostic power of blast enumeration as a proportion of NECs in MDS-erythroid, especially in the MDS without EB group and the lower-risk IPSS-R group. These findings were in line with the proposal of Leonor Arenillas et al.,6 who analyzed 465 MDS-erythroid patients and enumerated blasts systematically from NECs. Taken together, we found that enumerating the percentage of BM blasts from NECs significantly improved the prognostic assessment of MDS-erythroid, especially for patients within the intermediate risk group stratified by IPSS-R. This work was supported by grants from Jiangsu Province's Key Medical Center (ZX201102), Project of Natural Science Foundation of Jiangsu Province (BK20141201), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and the National Natural Science Foundation of China (81570138). YY and TZ contributed equally to this study. AS and SC were the principal investigators. QW, DW, JP, and JL performed most of the experiments. The authors declare no conflicts of interest. Additional Supporting Information may be found in the online version of this article. 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