WHO Makes MDS Classification Updates, Including Name Change

The fifth edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms includes multiple updates.

It renames myelodysplastic syndromes to myelodysplastic neoplasms (MDS) and makes several changes within the category.

The previous edition came out in 2008 and was revised in 2017. The fifth edition is “part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database,” according to an overview of the updates published in Leukemia by Joseph D. Khoury, MD, of the MD Anderson Cancer Center, and colleagues.

“The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions,” Dr. Khoury and colleagues wrote.

The fifth edition changes the name of MDS to refer to “neoplasms” instead of “syndromes,” “underscoring their neoplastic nature and harmonizing terminology” with myeloproliferative neoplasms (MPN), Dr. Khoury and colleagues wrote. It also adopts cytopenia definitions for consistency across clonal cytopenia of undetermined significance (CCUS), MDS, and MDS/MPN, with the recommended threshold for dysplasia now set at 10% for all lineages.

The updated classification now groups MDS entities by those that have defining genetic abnormalities and entities that are morphologically defined.

“It is posited that such reorganization enhances classification rigor by emphasizing genetically defined disease types and ceding the prior emphasis on ‘risk-based’ grouping in the classification (based on blast percentage, ring sideroblasts, and number of lineages with dysplasia) in favor of more comprehensive risk-stratification schemes such as the Revised International Prognostic Scoring System for MDS,” Dr. Khoury and colleagues wrote.

The fifth edition of the WHO classification updates MDS genetic types to include:

• MDS with low blasts and isolated 5q deletion (MDS-5q)
• MDS with low blasts and SF3B1 mutation (MDS-SF3B1)
• MDS with biallelic TP53 inactivation, which supersedes MDS-5q and MDS-SF3B1.

It now clarifies terminology to distinguish between MDS with low blasts from MDS with increased blasts “while retaining longstanding cutoffs,” according to Dr. Khoury and colleagues.

Regarding morphologically defined MDS, the fifth edition lists hypoplastic MDS as a distinct type of MDS.

The fifth edition now considers the distinction between single lineage and multilineage dysplasia to be optional rather than defining a specific type of MDS, as the “number of dysplastic lineages is usually dynamic and often represents clinical and phenotypic manifestation of clonal evolution,” Dr. Khoury and colleagues wrote.

It also removes MDS unclassifiable as an entity, as the updated MDS classification scheme and incorporation of CCUS into classification “obviates the need for ‘NOS’ or ‘unclassifiable’ attributes,” according to Dr. Khoury and colleagues.

While the fifth edition “softened” the boundary between MDS and acute myeloid leukemia (AML), it retains the 20% blast cutoff to define AML.

“Accordingly, a balanced approach was adopted by eliminating blast cutoffs for most AML types with defining genetic alterations but retaining a 20% blast cutoff to delineate MDS from AML,” Dr. Khoury and colleagues wrote. “Notwithstanding, there was broad agreement that MDS-IB2 may be regarded as AML-equivalent for therapeutic considerations and from a clinical trial design perspective when appropriate.”

The fifth edition also introduces “enhanced specificity of disease terminology” for childhood MDS, which excludes juvenile myelomonocytic leukaemia, myeloid proliferations associated with Down syndrome, and MDS that occurs after cytotoxic therapy.

“The qualifying term childhood MDS emphasizes that this category of myeloid neoplasms is biologically distinct from that seen in adults, underscoring the need to further elucidate its pathogenesis which remains incompletely understood,” Dr. Khoury and colleagues wrote.

Within the category, childhood MDS with low blasts replaces the former term “refractory cytopenia of childhood.” It includes two subtypes, childhood MDS with low blasts, hypocellular; and, childhood MDS with low blasts, not otherwise specified.

“Exclusion of non-neoplastic causes of cytopenia such as infections, nutritional deficiencies, metabolic diseases, bone marrow failure syndromes, and germline pathogenic variants remains an essential diagnostic prerequisite for childhood MDS with low blasts,” Dr. Khoury and colleagues wrote.

Reference

Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36(7):1703-1719.