Approach to myelodysplastic syndromes: Clinical sciences

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Introduction 0:00–0:39

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.

Unstable 0:39–1:42

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.

Stable1:42–3:18

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.

Assess for secondary causes3:18–4:33

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.

Myelodysplastic syndrome4:33–6:01

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.

Assess MDS type6:01–6:40

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!

MDS with 5q deletion6:40–7:04

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.

MDS with SF3B1 mutation7:04–7:34

Next, we have MDS with SF3B1 mutation! In these patients, the CBC will show reduced red blood cell count with low hemoglobin and hematocrit, as well as an elevated MCV, all of which depict macrocytic anemia.
However, their platelet and neutrophil count will usually be normal. If their cytogenetic and molecular testing reveals a mutation of SF3B1, you can diagnose MDS with SF3B1 mutation.Lastly, there’s MDS with biallelic TP53 inactivation!

MDS with biallelic TP53 inactivation7:34–8:16

If testing reveals inactivation of both copies of the TP53 tumor suppressor gene, the diagnosis is the MDS with biallelic TP53 inactivation.Here’s another high yield fact!
MDS patients with 5q deletion or SF3B1 mutation generally experience slower disease progression, and have a lower risk of developing acute myeloid leukemia or AML.
On the flip side, patients with biallelic TP53 inactivation are more prone to developing AML and thus tend to have a poor prognosis.

No defining genetic abnormalities present8:16–8:32

Alright, now let’s go back and have a look at MDS types associated with no defining genetic abnormalities. In such cases, assess the morphological characteristics of both the bone marrow and peripheral blood!Let’s start with hypoplastic MDS.

Hypoplastic MDS8:32–8:55

Let’s say your patient is presenting with pancytopenia, meaning low red blood cell count, low hemoglobin and hematocrit, low platelet and low white cell counts.
If the bone marrow examination reveals marked hypocellularity, you can diagnose hypoplastic MDS.Next, there is MDS with low blasts!

MDS with low blasts 8:55–9:09

In these patients, the bone marrow examination will show less than 5% of blasts, and less than 2% on the peripheral blood smear.
With these findings, you can diagnose MDS with low blasts.Finally, let’s have a look at MDS with increased blasts! In this case, the bone marrow examination will reveal blasts from 5 to 19% of blasts, and more than 2% on the peripheral blood smear.

MDS with increased blasts9:09–9:58

With these findings, you can diagnose MDS with increased blasts. One last clinical pearl!
The greater the number of blasts observed in MDS with increased blasts, the higher the degree of dysplasia in hematopoietic cells, and consequently, the greater the risk of transformation to Acute myeloid leukemia.
Distinguishing between MDS and AML comes down to the count of myeloblasts in the bone marrow or peripheral blood; if it's less than 20%, it's MDS, while if it's 20% or more, it's classified as AML.Alright, as a quick recap… Myelodysplastic syndromes are a group of hematologic neoplasms characterized by dysplasia and cytopenias, affecting blood cells of the myeloid cell lineage.

Review9:58–11:05

Symptoms vary depending on the affected blood cells, with anemic symptoms being more common. Once you suspect MDS, you need to rule out secondary causes, and confirm the presence of persistent cytopenias and the presence of dysplastic cells.
Additionally, there should be at least 10% of dysplastic cells and less than 20% of blasts. Once you confirm the diagnosis, assess the MDS type based on the presence of defining genetic abnormalities.
MDS types associated with genetic abnormalities include MDS with 5q deletion, MDS with SF3B1 mutation, and MDS with biallelic TP53 inactivation.
On the flip side, MDS types with no defining genetic abnormalities include hypoplastic MDS, MDS with low blasts,
Approach to myelodysplastic syndromes: Video | Osmosis