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Diagnosing MDS

Diagnosing and stratifying risk in MDS

MDS can be difficult to diagnose due to the resemblance to other hematologic disorders that have similar signs and symptoms, such as dysplasia and cytopenias. Performing clinical tests can help you establish a firm diagnosis of MDS.1

Assessing key hematologic parameters is essential to determine an accurate diagnosis of MDS. Further, the integration of molecular testing as determined in the IPSS-M system can improve risk stratification for patients with MDS.2

Assess risk stratification in MDS patients with IPSS-M down arrow

The combination of molecular testing and appropriate assessment of hematologic and cytogenetic parameters can help guide treatment decisions for patients.3

Causes of MDS4,5

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De novo MDS

Primary MDS originates spontaneously
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Secondary MDS

Secondary MDS occurs due to known risk factors including DNA-damaging therapy or environmental exposures and certain genetic conditions
Therapy-related MDS typically occurs as a result of previous radiation or chemotherapy for the treatment of cancer

MDS risk factors

The factors that are associated with an increased risk of developing MDS include4,6,7:

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Advanced age
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Male sex
Cancer icon
Prior treatment for cancer
Genetic icon
Genetic syndromes
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Familial MDS
Environment icon
Environmental exposures
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Smoking exposure

Signs and symptoms of MDS

Many patients are asymptomatic at diagnosis and are diagnosed only after incidental detection of cytopenias by their primary care physician during a routine blood test.4,7

Patients may present with one cytopenia or several. Anemia is the most common cytopenia detected in MDS, affecting nearly all patients at some point during their disease course.7,8

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Neutropenia image
Thrombocytopenia image

Diagnostic tests for MDS10

Blood tests

Measures the number of blood cells and platelets and may be useful in ruling out other conditions similar to MDS

Peripheral blood smears

Detects abnormalities in the size and appearance of blood cells

Immunophenotyping

Helps identify the type of MDS via examination of antigens

Bone marrow biopsy

Determines the percentage of blood cells including blasts and is useful to confirm a diagnosis of MDS

Cytogenetic tests

Detects specific abnormalities and is useful in distinguishing MDS from other disorders

Molecular tests

Detects mutations in specific genes unique to MDS and can help better classify MDS

Molecular testing can provide more insight into your patients’ MDS

Rapid PCR tests by platforms such as NeoGenomics can provide test results in under 4 days. It is recommended to repeat molecular testing at the first sign of disease progression as new mutations may be revealed.11-14

Evolving classification systems for MDS

Blast percentage has been commonly used to delineate MDS and AML with <20% defining MDS and ≥20% defining AML.7,15

Significant advances in the understanding of the molecular landscapes of MDS and AML prompted the need for classification systems to evolve. The International Consensus Classification (ICC) and the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours both address this need.16

WHO 2022

ICC 2022

Naming

Replaced myelodysplastic syndromes with myelodysplastic neoplasms (MDS)16

Retained original name:
myelodysplastic syndromes (MDS)16

Presence of ≥10% but <20% blasts

Renamed as MDS with increased blasts (MDS-IB2) (10%–19% blasts in bone marrow) previously known as MDS-EB-2 from WHO 201616

Introduced a new MDS/AML classification, defined as a cytopenic myeloid neoplasm and 10% to 19% blasts in the blood or bone marrow17

Genetic abnormalities

Most AML with defining genetic abnormalities can be diagnosed as AML, irrespective of blast count16

All entities are defined by recurrent genetic abnormalities (except BCR::ABL and TP53) and can be diagnosed as AML if ≥10% blasts are present16

New entities

Introduces hypoplastic MDS (MDSh) as a new entity that accounts for 10% to 15% of all MDS16

Not applicable

Patients with MDS/AML should be eligible for both MDS and AML clinical trials, which may inform treatment selections for these patients.17

Classifying MDS risk transformation to AML

Risk gauge pointing to low
Risk gauge pointing to high

Median survival6

3 to 10 years

less than 3 years

Typically characterized as:

Lower percentages of myeloblasts6
Some genetic variants are associated with a positive prognosis, such as SF3B16
Lesser degrees of cytopenias6
Higher percentage of myeloblasts6
Increased genetic variants associated with a worse prognosis, such as IDH1 and TP536,18
Greater degrees of cytopenias6

Risk of progression to AML4

5-15%
40-50%

~30%

of people progress from MDS to AML8

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Given the poor overall prognosis of MDS, there is an urgent need to provide potentially therapeutic options, which may include enrolling at-risk patients harboring a genetic mutation into clinical trials.6,19

International Prognostic Scoring System-Molecular (IPSS-M) for MDS

The number of genetic mutations affects risk stratification of patients with MDS in that a higher number of gene mutations is associated with worse outcomes.2

The discovery of numerous mutated genes and the impact of these genes on MDS survival over the past 10 years facilitated the need for an updated prognostic system in 2022: IPSS-M.2,19,20

Unlike IPSS-R, which was introduced in 2012 and focuses on hematologic and cytogenetic features only, IPSS-M also considers molecular mutations to determine an accurate risk stratification.2,19,20

Reclassification to IPSS-M from IPSS-R impacts survival prognoses2

>50% of patients
classified as IPSS-R intermediate shifted by one or more strata with IPSS-M, impacting survival prognoses2
Overall survival chart Overall survival chart
aRisk was encoded using the five categories for both IPSS-R and IPSS-M by merging the moderate low and moderate high categories for the intermediate group.2

The inclusion of clinical data, cytogenetics, and molecular data—including residual genesb such as IDH1 mutations—is critical to stratify your MDS patient in the correct risk category.2

bResidual genes are defined as genes with residual effects that cannot be estimated when these genes are individually selected in the risk prediction model.2

Clinical data2

Bone marrow blasts (%)
Hemoglobin (g/dL)
Platelets (x109/L)

Molecular data2

Gene mutations such as IDH1, NF1, ASXL1, and DNMT3A

Cytogenetics21

Presence or absence of chromosome abnormalities
del (5q)
-7/del(7q)
-17/del(17p)
Complex karyotype

Please refer to the latest IPSS-M to assess a patient risk score for MDS based on the full guidance.

Assess your patients’ risk in MDS using the IPSS-M risk stratification tool.

Review treatment goals for lower-risk MDS and higher-risk MDS
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AML, acute myeloid leukemia; IPSS-R, International Prognostic Scoring System-Revised; MDS, myelodysplastic syndromes.

References: 1. Sekeres M. Patient education: myelodysplastic syndromes (mds) in adults (beyond the basics). UpToDate. Updated November 2, 2022. Accessed July 19, 2023. www.uptodate.com/contents/myelodysplastic-syndromes-mds-in-adults-beyond-the-basics. 2. Bernard E, Tuechler H, Greenberg PL, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evid. 2022;1(7). doi:10.1056/evidoa2200008 3. Pagliuca S, Gurnari C, Visconte V. Molecular targeted therapy in myelodysplastic syndromes: new options for tailored treatments. Cancers (Basel). 2021;13(4):784. doi:10.3390/cancers13040784 4. Kantarjian H, Giles F, List A, et al. The incidence and impact of thrombocytopenia in myelodysplastic syndromes. Cancer. 2007;109(9):1705-1714. doi:10.1002/cncr.22602 5. Causes. Aplastic Anemia & MDS International Foundation. Accessed July 19, 2023. https://www.aamds.org/diseases/mds/causes 6. Sekeres MA, Taylor J. Diagnosis and treatment of myelodysplastic syndromes: a review. JAMA. 2022;328(9):872-880. doi:10.1001/jama.2022.14578 7. Aster JC. Clinical manifestations and diagnosis of myelodysplastic syndromes (MDS). UpToDate. Updated March 24, 2023. Accessed July 19, 2023. https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-classification-of-myelodysplastic-syndromes-mds 8. Gangat N, Patnaik MM, Tefferi A. Myelodysplastic syndromes: contemporary review and how we treat. Am J Hematol. 2016;91(1):76-89. doi:10.1002/ajh.24253 9. Toma A, Fenaux P, Dreyfus F, Cordonnier C. Infections in myelodysplastic syndromes. Haematologica. 2012;97(10):1459-1470. doi:10.3324/haematol.2012.063420 10. Myelodysplastic syndromes - MDS: diagnosis. Cancer.Net. Approved May 2023. https://www.cancer.net/cancer-types/myelodysplastic-syndromes-mds/diagnosis 11. Platzbecker U, Kubasch AS, Homer-Bouthiette C, Prebet T. Current challenges and unmet medical needs in myelodysplastic syndromes. Leukemia. 2021;35(8):2182-2198. doi:10.1038/s41375-021-01265-7 12. Bewersdorf JP, Xie Z, Bejar R, et al. Current landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) of the International Consortium for MDS (icMDS). Blood Rev. 2023;60:101072. doi:10.1016/j.blre.2023.101072 . 13. Data on file. Servier Pharmaceuticals LLC. 14. Rapid AML therapeutic panel. NeoGenomics Laboratories. Accessed July 19, 2023. https://neogenomics.com/test-menu/rapid-aml-therapeutic-panel 15. Estey E, Hasserjian RP, Döhner H. Distinguishing AML from MDS: A fixed blast percentage may no longer be optimal. Blood. 2022;139(3):323-332. doi:10.1182/blood.2021011304 16. Falini B, Martelli MP. Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia. Am J Hematol. 2023;98(3):481-492. doi:10.1002/ajh.26812 17. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140(11):1200-1228. doi:10.1182/blood.2022015850 18. Thol F, Weissinger EM, Krauter J, et al. IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Haematologica. 2010;95(10):1668-1674. doi:10.3324/haematol.2010.025494 19. Nazha A, Sekeres MA, Gore SD, Zeidan AM. Molecular testing in myelodysplastic syndromes for the practicing oncologist: Will the progress fulfill the promise? Oncologist. 2015;20(9):1069-1076. doi:10.1634/theoncologist.2015-0067 20. Caponetti GC, Bagg A. Mutations in myelodysplastic syndromes: core abnormalities and CHIPping away at the edges. Int J Lab Hematol. 2020;42(6):671-684. doi:10.1111/ijlh.13284 21. IPSS-M Risk Calculator. mds-risk-model.com. Accessed July 19, 2023. https://mds-risk-model.com/