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Side Effect: Differentiation Syndrome

What is Differentiation Syndrome?

What does Differentiation Syndrome look like?

Differentiation syndrome typically presents within 10-14 days of starting treatment with drugs that induce cellular differentiation.

The symptoms can vary, but commonly include:

The symptoms can progress rapidly, and if left untreated, differentiation syndrome can cause critical illness and even be fatal.

Who gets Differentiation Syndrome?

Patients with an elevated white blood cell count (WBC) and certain types of leukemia are at highest risk. In addition, not all anti-leukemia treatments increase the risk of differentiation syndrome, but here are some that may:

It is estimated that 10-25% of patients with acute promyelocytic leukemia (APL) or acute myeloid leukemia (AML) will develop differentiation syndrome when treated with the medications listed above.

How to prevent Differentiation Syndrome

Patients with AML are closely monitored for signs and symptoms during their initial treatment, known as induction therapy.

While not routinely offered to everyone, certain patients being treated for APL who are considered to be at an increased risk for differentiation syndrome may receive corticosteroids such as prednisone (Deltasone®) or dexamethasone (Decadron®) during induction therapy to provide anti-inflammatory effects to help prevent differentiation syndrome.

In some instances when the WBC is elevated, hydroxyurea (Hydrea®) may be utilized before or during therapy to help lower the WBC and lessen risk of differentiation syndrome.

How to treat Differentiation Syndrome


1. Gasparovic L, Weiler S, Higi L, Burden AM. Incidence of Differentiation Syndrome Associated with Treatment Regimens in Acute Myeloid Leukemia: A Systematic Review of the Literature. J Clin Med. 2020;9(10):3342.

2. Sanz MA, Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. Blood. 2014;123(18): 2777–2782.

Created: May 18, 2024 Updated: May 18, 2024