Differentiation syndrome (DS; originally called “retinoic acid syndrome”) is a potentially fatal complication of treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid and/or arsenic trioxide, treatment of acute myeloid leukemia (AML) with inhibitors of isocitrate dehydrogenase (IDH; eg, IDH2 inhibitor, enasidenib; IDH1 inhibitor, ivosidenib), and treatment of AML with mutant FLT3 (Fms-related tyrosine kinase 3) with gilteritinib, and menins.
Differentiation syndrome occurs when the rapid transformation of leukemia cells into mature white blood cells leads to a systemic inflammatory response in the body.
Symptoms of differentiation syndrome can include fever, respiratory distress, weight gain, fluid retention, low blood pressure, and organ dysfunction.
If differentiation syndrome is suspected, treatment may involve temporarily stopping the associated medication, administering corticosteroids to reduce inflammation, and providing supportive care to manage symptoms.
Early recognition and prompt management of differentiation syndrome are crucial to prevent complications and improve patient outcomes.
DS occurs in roughly one-quarter of patients with acutepromyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and/orarsenic trioxide (ATO), up to one-fifth of patients treated with ivosidenib or for acute myeloid leukemia (AML), and a small fraction of those treated with gilteritinib.
Factors that predict development of DS are not well defined.
Acute promyelocytic leukemia – DS is reported in approximately one-quarter of patients who are treated with ATRA for APL, butthe incidence has ranged from 2 to 48 percent; the wide range in incidence reflects differences in induction regimens, preventive measures, and different diagnostic criteria .
For patients treated with ATO for APL, the incidence ofDS ranged from 7 to 31 percent .
DS can also occur in patients with relapsed APL who were treated with ATRA and/or ATO .
DS has not been reported with ATO treatment ofnon-APL malignancies or during consolidation or maintenance phase of APL, because the syndrome depends on the presence of leukemic blasts and/or promyelocytes .