Approach to myelodysplastic syndromes: Clinical sciences

Myelodysplastic syndromes or MDS, refers to a group of hematologic neoplasms associated with impaired hematopoiesis. Platelets, red blood cells, and neutrophils are the most common cell lines affected by MDS, which manifests with dysplasia, or abnormal blood cell morphology, along with cytopenia, which refers to a decrease in blood cell count. Now, there are various types of MDS, which are classified based on the presence of defining genetic abnormalities, or morphologic characteristics of the bone marrow or peripheral blood.

Now, if your patient presents a chief concern suggesting MDS, first perform an ABCDE assessment to determine if they’re unstable or stable. If they’re unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry. Finally, if needed, don’t forget to provide supplemental oxygen.

Now, here’s a clinical pearl! There are several ways that a patient with MDS can present as unstable. First, MDS can cause severe thrombocytopenia, which may result in intracranial or gastrointestinal bleeding. Second, MDS can cause neutropenia, leading to fungal and bacterial infections, such as pneumonia and sepsis. Lastly, MDS can transform into acute myeloid leukemia, which can cause tumor lysis syndrome, or acute disseminated intravascular coagulation.

Now, let’s return to the ABCDE assessment and take a look at stable patients. In this case, obtain a focused history and physical exam, and order labs including a complete blood count with differential. Your patient will usually be over 60 years old, and symptoms will vary depending on the type of affected blood cells. If red blood cells are affected, they might report symptoms of anemia, like fatigue, shortness of breath on exertion, and palpitations. Interestingly, anemia is the most common cytopenia associated with MDS, and is generally associated with an inappropriately low reticulocyte response.

Now, if platelets are affected, your patient might report easy bruising or bleeding. Additionally, if their neutrophil count is reduced, they’ll present with a history of frequent bacterial infections, such as pneumonia. Lastly, these patients can present with a history of prior chemotherapy, radiation therapy, or use of immunosuppressive medications.

Next, the physical exam will likely reveal tachycardia and conjunctival pallor, and in some cases, petechiae, purpura, and ecchymosis. Finally, the CBC will typically show a low red blood cell count, along with low hemoglobin and hematocrit, indicating that the patient has anemia. In some cases, the CBC might reveal other cytopenias, including low platelet and neutrophil count. With these findings, you should consider MDS.

Now, before confirming MDS as the underlying cause of cytopenia, first, you should assess for, and rule out possible secondary causes of cytopenia. There are many causes of secondary cytopenias. For example, anemia can arise from nutrient deficiency, hemolysis, or splenic sequestration of red blood cells. Next, thrombocytopenia can be caused by medications, such as antibiotics or anticonvulsants, or underlying conditions like sepsis or chronic liver disease.

Lastly, neutropenia can be caused by cytotoxic or immunosuppressive medications, like calcineurin inhibitors, or various kinds of infections, such as HIV. If you identify a secondary cause, diagnose secondary cytopenia. However, if you rule out secondary cytopenias, your next step is to repeat the CBC over the next few months. This is because you might need additional time to determine if your patient’s cytopenia is really persistent. Additionally, you should obtain a peripheral smear, and a bone marrow biopsy or aspirate for examination.

Let’s take a look at our results. If the repeat CBC shows no cytopenia, or the peripheral smear shows no evidence of dysplasia, or the bone marrow examination reveals more than 20% of blasts, you should consider an alternative diagnosis. On the other hand, if the CBC reveals persistent cytopenias; peripheral smear shows dysplastic blood cells, and bone marrow reveals dysplasia in one or more lineages, with dysplastic cells being over 10%, and blasts being less than 20%, diagnose MDS.

Now, here’s a high-yield fact! In MDS, certain dysplastic changes that can be identified on a peripheral blood smear. These include hypo- or hypersegmented neutrophils; large platelets with abnormal granules; and abnormally large and elliptical red blood cells known as macroovalocytes and elliptocytes. You typically also see teardrop cells, also called dacrocytes.

On the other hand, the bone marrow examination may reveal megakaryocytes with multiple scattered nuclei and abnormal granules. As well as granulocyte precursors with larger and irregular nuclei, and erythroid cells with multilobed nuclei and large vacuoles.

Now, once you diagnose MDS, your next step is to assess its type using the World Health Organization classification system. This system categorizes MDS types based on the presence of defining genetic abnormalities, or bone marrow morphology. To do this, you’ll need to order bone marrow cytogenetic and molecular testing. This may include karyotyping, fluorescence in-situ hybridization or FISH, PCR, and DNA sequencing. These diagnostic tests will help determine presence or absence of defining genetic abnormalities.

Now, let’s take a look at MDS types associated with defining genetic abnormalities, starting with 5q deletion! These patients are usually biological females with an advanced age, usually over 70 years of age. If cytogenetic and molecular testing reveals a 5q chromosomal deletion, then diagnose MDS with 5q deletion.