What is Differentiation Syndrome?

What is differentiation syndrome?

Differentiation syndrome is a rare condition that occurs in people being treated for certain types of acute leukemia: acute promyelocytic leukemia (APL) and other types of acute myeloid leukemia (AML).  Differentiation syndrome occurs shortly after treatment with certain types of medication. It can start as soon as one day after treatment begins. It typically starts within 1 to 3 weeks, but it can start a few months after treatment. It is most common in people with a low white blood cell count.  Differentiation syndrome can become life-threatening, so it is important that it is identified and treated early.  

What causes differentiation syndrome?

For people with AML, immature blood cells from the bone marrow or blood (blast cells) do not fully develop into mature cells. Instead, the abnormal cells continue to multiply and prevent mature blood cells from functioning properly.  

Read more about AML.

Differentiation agents are a class of medications used to treat certain types of leukemia. They work by causing these immature white cells to mature into normal functioning white blood cells.  Providers use these therapies alone or in combination with other medications.

Some standard differentiation agents used for treating leukemia are all-trans retinoic acid (ATRA) and arsenic trioxide. 

IDH inhibitors are also used to treat AML. An IDH inhibitor is a targeted therapy that blocks certain enzymes (IDH1 and IHD2) that prevent leukemia cells from maturing.  

These therapies can lead to rapid release of cytokines (proteins that regulate immune responses like inflammation) which triggers differentiation syndrome.   

What are the symptoms of differentiation syndrome?

Differentiation syndrome can look different from person to person. The symptoms may be minor at first or become severe, and they can develop quickly.  

Common symptoms of differentiation syndrome include:

• Fever
• Difficulty breathing
• Low blood pressure
• Weight gain 
• Build up of fluid around the heart and lungs
• Acute kidney injury

If any of these symptoms happen while taking a differentiation agent, it’s important to contact your care team right away because DS is more manageable the earlier it is recognized.  

What is the treatment for differentiation syndrome?

Treatment for differentiation syndrome depends on the severity of the condition. Once differentiation syndrome has been diagnosed, the most common treatment approach is dexamethasone, a corticosteroid used to treat inflammation.  

If the case is more severe, your provider may recommend stopping treatment of the differentiating agent until differentiation syndrome is resolved.  

If you’re experiencing swelling, your provider may also prescribe furosemide, a diuretic used to treat fluid retention.  

Being aware of the symptoms of differentiation syndrome and communicating with your care team can help prevent serious problems and keep your treatment on track.

Follow the link below to continue reading news about AML. 

Read More AML News

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Sources: 

• Differentiation Syndrome in Acute Leukemia: APL and Beyond
• Cleveland Clinic-Differentiation Syndrome 
• National Cancer Institute: Differentiation Syndrome Definition 
• Differentiating agents in the treatment of leukemia 
• HealthTree-What is AML 
• How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia 
• Efficacy and safety of IDH inhibitors in IDH-mutated cancers