What are the diagnostic and treatment approaches for Myeloproliferative Neoplasms (MPN) and Myelodysplastic Syndromes (MDS)?

From the Guidelines

Diagnosis of Myeloproliferative Neoplasms (MPN) and Myelodysplastic Syndromes (MDS) should be approached with a comprehensive strategy incorporating laboratory tests, bone marrow evaluation, and genetic analysis, prioritizing the most recent guidelines from reputable sources such as the European LeukemiaNet or the American College of Medical Genetics and Genomics 1.

Diagnostic Approach

For MPN and MDS diagnosis, the following steps are crucial:

• Complete blood count (CBC) to identify cytopenias or cytoses
• Peripheral blood smear to evaluate cell morphology
• Bone marrow aspiration and biopsy for histopathological examination and cytogenetic analysis
• Genetic testing for specific mutations (e.g., JAK2, CALR, MPL in MPNs; cytogenetic abnormalities in MDS)

Genetic Testing

Genetic testing plays a pivotal role in the diagnosis and risk stratification of both MPN and MDS. For MDS, cytogenetic analysis, including conventional karyotyping and fluorescence in situ hybridization (FISH), is essential to identify chromosomal abnormalities that can influence prognosis and treatment decisions 1. The use of next-generation sequencing (NGS) can also detect somatic mutations that are relevant for diagnosis and prognosis.

Risk Stratification and Treatment

Treatment strategies for MPN and MDS vary based on the specific subtype and risk category:

• For MPNs, treatment is subtype-specific: phlebotomy and low-dose aspirin for polycythemia vera, hydroxyurea for essential thrombocythemia, and ruxolitinib for primary myelofibrosis.
• For MDS, the IPSS-R system guides treatment decisions, with lower-risk patients potentially receiving erythropoiesis-stimulating agents and higher-risk patients requiring hypomethylating agents like azacitidine or decitabine.

Ongoing Monitoring

Regular follow-up with blood counts and periodic bone marrow examinations is necessary to monitor disease progression and the potential transformation to acute myeloid leukemia (AML), adjusting treatment as needed to manage symptoms, prevent complications, and maintain quality of life 1.

Recent Guidelines

The most recent guidelines, such as those from the American College of Medical Genetics and Genomics 1 and the European Society for Medical Oncology (ESMO) 1, emphasize the importance of a multidisciplinary approach to diagnosis and treatment, incorporating the latest in genetic and cytogenetic analysis to personalize care for patients with MPN and MDS. The diagnostic workup should always prioritize the exclusion of non-malignant causes of cytopenias and the identification of specific genetic markers that can guide treatment decisions and predict outcomes 1.

From the FDA Drug Label

1.5 Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) 2.6 Adult Patients With MDS/MPD

The diagnostic approach for Myeloproliferative Neoplasms (MPN) and Myelodysplastic Syndromes (MDS) is not explicitly stated in the provided drug label. However, it mentions Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) as an indication for the use of interferon-alpha (IM).

• The label does not provide a clear diagnostic criteria for MPN or MDS.
• It only mentions the use of interferon-alpha (IM) in adult patients with MDS/MPD, without specifying how the diagnosis is made 2.

From the Research

Diagnostic Approaches for MPN and MDS

• The diagnosis of Myeloproliferative Neoplasms (MPN) and Myelodysplastic Syndromes (MDS) involves a combination of clinical, laboratory, and genetic evaluations 3, 4, 5, 6, 7.
• Morphological examination of bone marrow aspirate and biopsy is essential for diagnosing MDS, while MPN diagnosis relies on the presence of specific genetic mutations, such as JAK2V617F 4, 5.
• Laboratory tests, including cytochemistry, immunohistochemistry, flow cytometry, and genetic testing, are used to exclude other disorders and confirm the diagnosis of MDS/MPN overlap syndromes 7.

Key Diagnostic Features of MDS/MPN Overlap Syndromes

• Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is characterized by the presence of ring sideroblasts, thrombocytosis, and specific genetic mutations, such as SF3B1 and JAK2V617F 3, 4.
• Chronic myelomonocytic leukemia (CMML) is marked by sustained peripheral blood monocytosis and recurrent mutations involving TET2, SRSF2, and ASXL1 6.
• Atypical chronic myeloid leukemia (aCML) and myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U) are other subcategories of MDS/MPN overlap syndromes, each with distinct clinical and genetic features 6, 7.

Treatment Approaches for MPN and MDS

• Treatment of MDS and MPN depends on the specific diagnosis, risk stratification, and patient characteristics 4, 5, 6.
• Options for MDS include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation 5.
• For MPN, treatment may involve cytoreduction, bone marrow stimulating agents, and JAK inhibitors, as well as allogeneic stem cell transplantation in selected cases 3, 4.
• Newer therapeutics, such as luspatercept, have been approved for the management of anemia in patients with MDS-RS and MDS/MPN-RS-T 4.