The Placement of Auer Rods as a Single Diagnostic Criterion for the Highest-Risk Category of Myelodysplastic Syndromes: A Single-Institution Study and Critical Analysis

Accurate determination of prognostic risk is critical for patients and treating clinicians. The French-American-British classification of myelodysplastic syndromes (MDS) described refractory anemia with excess blasts (RAEB) in transformation (RAEB-T), including two subsets with <20% bone marrow (BM) blasts, which were reclassified as RAEB-2, the highest-risk MDS category in the 2001 World Health Organization classification. Those diagnostic criteria have been retained until now with nomenclature changes from RAEB-2 to “MDS with excess blasts-2” in 2017 and “MDS with increased blasts-2” (MDS-IB2) in 2022. The placement of Auer rods (AR) in the diagnostic classification has been controversial since its inception. This single-institution retrospective study analyzed 22 consecutive de novo MDS patients with <20% BM blasts originally diagnosed as RAEB-T only due to AR (n = 13) or ≥5% peripheral blood (PB) blasts ± AR (n = 9), applying the International Prognostic Scoring System (IPSS) and revised-IPSS (IPSS-R) for MDS. The AR-positive group showed 67% males, younger age (p = 0.01), median 8.4% (range 2.6–15.0) BM blasts, 58% normal (0% complex) karyotypes, and low/int-1 IPSS in all (100%) patients with <5% BM blasts compared with the ≥5% PB blast group with 55% females, median 10.5% (range 5.4–15.0) BM blasts, 67% abnormal (17% complex) karyotypes, and high/very high-risk IPSS-R (83%). Auer rod-positive MDS was associated (p = 0.01) with BM transplant referral/procedure but not (p = 0.88) with acute leukemia development. This small study suggests that Auer rod-positive MDS is likely distinct from Auer rod-negative MDS and genetically from MDS with ≥5% PB blasts. A critical analysis shows high-risk IPSS-R scores in previously reported patients with AR-positive MDS and <5% BM blasts, confirming that IPSS-R variables, not Auer rods, accounted for their adverse outcomes. Despite recent studies, genomic features of Auer rod-positive MDS patients with low blast percentages are unknown. No rationale is identified in this study and analysis for placing Auer rods as a diagnostic criterion for the highest-risk diagnostic category of MDS. Additional studies are warranted incorporating genomic analyses and other clinical, hematologic, and genetic variables, specifying BM blast percentages, to ascertain if Auer rods have any place in the diagnostic classification of MDS.