Dr Loghavi on SOC Frontline Testing Approaches in MDS

"Right now, the standard-of-care testing for a patient with suspected MDS is to get a bone marrow aspirate and a biopsy for morphologic evaluation at some centers. It's not universally done, but we have specialized flow cytometry that [looks] for immunophenotypic aberrations and hematopoietic stem cells."

Sanam Loghavi, MD, an assistant professor in the Department of Hematopathology, Division of Pathology/Lab Medicine, at The University of Texas MD Anderson Cancer Center, discusses standard-of-care (SOC) frontline testing strategies for patients with suspected myelodysplastic syndrome (MDS).

Loghavi began by explaining that the current SOC approach to frontline testing generally involves obtaining a bone marrow aspirate and a biopsy for comprehensive morphologic evaluation, although this practice can vary among centers and is not universally performed. Specialized flow cytometry is also utilized to identify immunophenotypic aberrancies within hematopoietic stem cells, Loghavi added.

A critical and intricate component of diagnosis is the genetic evaluation of the disease, which is characterized as a complex and multifactorial landscape, Loghavi continued. This comprehensive genetic assessment includes karyotyping, a method specifically designed to analyze the chromosomal structure for abnormalities inherent to MDS, she explained. For example, MDS with a deletion 5q abnormality is defined by this specific karyotypic finding, Loghavi noted. Furthermore, next-generation sequencing is employed to screen for somatic mutations, she said.

Loghavi then highlighted 2 specific types of mutations as being particularly significant due to their therapeutic relevance: SF3B1 and TP53. SF3B1 mutations are associated with the presence of ring sideroblasts and a distinct disease phenotype that typically responds to luspatercept-aamt (Reblozyl), Loghavi explained. In contrast, TP53 alterations pose a considerable challenge, as they are not currently linked to an effective targeted therapy and are instead strongly associated with a very poor prognosis and adverse patient outcomes, she said. For eligible individuals presenting with TP53 alterations, an early bone marrow transplant is often recommended within the disease course to prevent progression to acute myeloid leukemia and mitigate the risk of premature death, Loghavi concluded.