Pathophysiology, clinical features and radiological findings of differentiation syndrome/all-trans-retinoic acid syndrome

Table 1 Signs and symptoms

Differentiation syndrome: Sign and symptoms
Elevated white blood cell count	Weight gain > 5 kg
Dyspnea	Bone pain
Respiratory distress	Headache
Fever	Hypotension
Pulmonary edema	Congestive heart failure
Pulmonary infiltrates	Acute renal failure
Pleural and pericardial effusion	Hepatotoxicity

Table 2 Measures at suspicion of differentiation syndrome

Measures at suspicion of DS

Chest X-ray, renal function (creatinine and urea), hepatic function (amino transferases and bilirubin), blood cell counts, coagulation test, oxygen saturation

Weight monitoring

Ventilatory support/O2 supplementation

Blood pressure maintenance measures

Fluid restriction (renal failure)

Steroid administration at first suspicion: dexamethasone 10 mg twice daily until clinical resolution, then tapered dose for a few days

Suspend ATRA or ATO in severe cases, which can be restarted after clinical improvement. If DS recurs after restart, ATRA must be definitively discontinued during induction

Some patients have DS that is refractory to corticosteroids. There are yet no widely accepted alternatives to it. It seems reasonable to employ, in the future, agents that block migration, adhesion or transmigration of APL cells. References: Institute of Radiology, Department of Clinical and Biological Sciences of University of Turin, AOU S.Luigi Gonzaga, Regione Gonzole 10, 10043 Orbassano, Torino, Italy. DS: Differentiation syndrome; ATRA: All-trans-retinoic acid; ATO: Arsenic-trioxide.