Dr Robert Hasserjian

Summary

In this talk, the speaker discusses the evolution and complexities of Myeloid Neoplasms (MDS and AML) classifications since 2016. They highlight the split in 2022, resulting in two concurrent classifications by WHO and ICC. While many entities remain consistent, significant differences and new entities are noted, especially in diagnostic criteria for MDS and AML. The speaker emphasizes the need for hematopathologists, clinicians, and pharmaceutical companies to be familiar with both schemes, as differences impact disease definitions and treatment approaches. The talk concludes with insights into the future of myeloid classifications and the importance of ongoing research and alignment.

Takeaways

• 😊 The speaker is honored to discuss MDS and AML classifications, acknowledging the evolution since 2016.
• 📚 In 2022, two new myeloid classifications were issued by different groups, one in 'Blood' and one in 'Leukemia,' creating complexity.
• 🧬 Both classifications, despite some differences, maintain many identical or similar entities, especially for MDS and AML.
• 🔬 Hematopathologists should provide both classifications to clinicians, pharmaceutical companies, and regulatory agencies for comprehensive understanding.
• 🧪 Both classifications recognize clonal cytopenias and acknowledge conditions like PNH and VEXAS syndrome but distinguish them from MDS.
• 🧩 Dysplasia remains the key diagnostic feature to separate MDS from other conditions, though it's imperfect and somewhat subjective.
• 🧠 The ICC and WHO introduced genetic entities like MDS with mutated SF3B1 and TP53, focusing on genetic mutations rather than morphological features.
• 🔄 A new category, MDS-AML overlap, recognizes cases with 10-19% blasts, acknowledging a continuum between MDS and AML.
• 🔍 Morphological subtypes like hypoplastic MDS and MDS with fibrosis have been added, highlighting specific prognostic and treatment considerations.
• 💡 The classifications aim to provide a comprehensive diagnostic framework, considering both genetic and morphological factors to benefit patient outcomes.

Q & A

What is the primary topic of the speaker's presentation?

The primary topic of the speaker's presentation is MDS (Myelodysplastic Syndromes) and AML (Acute Myeloid Leukemia) classifications.

What significant event in the classification of MDS and AML occurred in 2022?

In 2022, there was a split resulting in two new classifications of MDS and AML being issued, one published in Blood and the other in Leukemia.

How do the two classifications of MDS and AML issued in 2022 differ in their approach?

While many entities are identical or similar in both classifications, there are significant differences in nomenclature, diagnostic criteria, and the recognition of some new entities.

What is the significance of the SF3B1 mutation in MDS classification?

The SF3B1 mutation is significant in MDS classification as it defines a more homogeneous entity of MDS with mutated SF3B1, which is associated with a favorable prognosis. Both the WHO and ICC classifications recognize this genetic MDS group.

What is the ICC's stance on the use of dysplasia to separate MDS from clonal cytopenias?

The ICC acknowledges that dysplasia is somewhat subjective and an imperfect feature, but it remains the best diagnostic test currently available to separate MDS from clonal cytopenias.

How does the ICC classification handle TP53 mutated MDS?

The ICC classification recognizes TP53 mutated MDS as a primary aggressive disease entity with poor prognosis, characterized by complex karyotypes and genomic instability.

What is the new category introduced by the ICC for cases with 10-19% blasts?

The ICC introduced a new category called MDS/AML overlap group for cases with 10-19% blasts, acknowledging an intermediate group that may benefit from intensive AML-type chemotherapy.

What changes did the WHO make regarding hypoplastic MDS and MDS with fibrosis?

The WHO introduced two new morphologic subgroups: hypoplastic MDS, defined by low cellularity, and MDS with fibrosis, defined by increased blasts and grade 2 or 3 reticulin fibrosis, both with potential prognostic significance.

How does the ICC classification approach AML with specific genetic features even if blasts are below 20%?

The ICC classification allows for the diagnosis of AML with specific genetic features (e.g., NPM1 mutation) even if blasts are below 20%, provided there is at least 10% blasts, to avoid treating stable cases with low blast counts.

What is the expected outcome of having two different classifications for MDS and AML according to the speaker?

The speaker hopes that the differences between the two classifications will spawn research to refine and improve the next classification, ultimately leading to a single, stronger classification system for myeloid neoplasms.