Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a rare and complex blood disorder. It is categorized as a hybrid condition, displaying characteristics of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). This article covers its features, diagnosis, treatment, and general outlook.
What is MDS/MPN-RS-T?
MDS/MPN-RS-T is a myelodysplastic/myeloproliferative neoplasm, a group of disorders affecting blood cell production in the bone marrow. The acronym stands for Myelodysplastic Syndromes (MDS), Myeloproliferative Neoplasms (MPN), Ring Sideroblasts (RS), and Thrombocytosis (T). This condition combines features where the bone marrow produces blood cells inefficiently (MDS) while also overproducing certain mature blood cells (MPN).
A defining feature of MDS/MPN-RS-T is the presence of “ring sideroblasts” in the bone marrow. These are immature red blood cells (erythroid precursors) that have abnormal iron accumulation in their mitochondria, forming a ring around the nucleus. For a cell to be classified as a ring sideroblast, five or more iron granules must encircle at least one-third of the nucleus.
Individuals with this condition also exhibit thrombocytosis, an elevated platelet count typically above 450 x 10^9/L. Genetic mutations underlie MDS/MPN-RS-T, with the SF3B1 mutation present in approximately 80% of cases. This SF3B1 mutation is co-mutated with JAK2 V617F in over 50% of cases.
Recognizing the Signs
The symptoms associated with MDS/MPN-RS-T can vary among individuals and are often not specific to this condition. Many symptoms arise from low blood cell counts, particularly anemia. Anemia can lead to fatigue, weakness, shortness of breath, and pallor, an unusual paleness of the skin.
While thrombocytosis is a characteristic of this condition, bleeding or clotting issues due to high platelet counts are less common than in other myeloproliferative neoplasms. Some individuals may also experience general symptoms, such as unintended weight loss, fever, or night sweats, often referred to as B symptoms. An enlarged spleen (splenomegaly) can also be present.
It is important to remember that these symptoms are not unique to MDS/MPN-RS-T and can be indicative of many other medical conditions. Experiencing these signs warrants a medical evaluation to determine the underlying cause and receive appropriate care.
How it’s Diagnosed
The diagnostic process for MDS/MPN-RS-T begins with blood tests. A complete blood count reveals an elevated platelet count (thrombocytosis) at or above 450 x 10^9/L, and may show anemia. The red blood cells might display two distinct populations and vary in size.
Bone marrow biopsy and aspiration are key for diagnosis. This procedure allows for a microscopic examination of the bone marrow cells, where the presence of ring sideroblasts is identified. The bone marrow shows hypercellularity with increased and atypical megakaryocytes, along with dyserythropoiesis.
Genetic testing plays a key role in confirming the diagnosis and ruling out other similar conditions. The SF3B1 mutation is found in approximately 80% of cases. Other molecular studies, such as testing for the JAK2 V617F mutation and cytogenetic analysis, are also performed.
Managing the Condition
Management of MDS/MPN-RS-T is individualized, considering symptoms, disease progression, and other health factors. Supportive care is a key aspect of treatment, including blood transfusions to manage anemia and improve fatigue. Iron chelation therapy may be used for iron overload from frequent transfusions.
Specific medications address different aspects of the condition. For anemia, erythropoiesis-stimulating agents (ESAs) are a first-line treatment, particularly for those requiring regular red blood cell transfusions. Luspatercept, an erythroid maturation agent, is approved for managing anemia in transfusion-dependent patients with lower-risk MDS-RS and MDS/MPN-RS-T.
If myeloproliferative features are prominent, such as an enlarged spleen or general body symptoms, JAK inhibitors like ruxolitinib may be considered. Lenalidomide has also shown positive outcomes in some cases of MDS/MPN-RS-T. Hypomethylating agents, such as azacitidine and decitabine, may also be used. While there is no standard cure, treatment aims to manage symptoms, improve the quality of life, and in some cases, delay disease progression.
Understanding the Outlook
MDS/MPN-RS-T is considered a chronic condition, and its course is less aggressive compared to some other subtypes of MDS or MPN. The median overall survival for individuals with MDS/MPN-RS-T is approximately 76 to 128 months. Factors influencing prognosis include patient age and the presence of specific genetic mutations, such as SF3B1 and JAK2 V617F, with younger patients having both mutations sometimes showing better outcomes.
While the risk of progression to acute myeloid leukemia (AML) exists, it is lower in MDS/MPN-RS-T than in some other MDS subtypes. Regular monitoring and follow-up care are important to track disease progression, manage complications that arise, and adjust treatment strategies as needed.