Differentiation Syndrome in APML

Epidemiology:

 • Incidence: common in APL (2-48% depending on the study)

 • Triggers: ATRA treatment

Pathophysiology:

 • Cytokine Release from blast cells → SIRS response

 • Cathepsin G release → vascular permeability and endothelial damage

 • Induce blast cell adhesion and endothelial damage

Prophylaxis:

 • Attempt if high risk if WBC > 5 or elevated Cr

 • Prednisone 5mg/kg/day vs. 2.5 mg/m2

Presentation: Subacute-Acute:

 • Common: fever, myalgias, HoTN, edema and effusions, weight gain. More common in severe

 • Rare: DAH, acute febrile neutrophilic dermatosis

Diagnosis:

 • Labs: leukocytosis and coagulopathy common

 • Imaging: CXR- pulmonary opacities

 • Diagnosis: >3 symptoms, or> 1 with no other explanation. Moderate > 2/3 and severe >4. Timing, generally either within 6 days or 15 days of ATRA initiation

 • Differential Diagnosis: Infection (sepsis), PE, DAH, CHF, Anaphylaxis, Acute Renal Failure

Treatment:

 • Steroids: IV Dexamethasone 10 mg q12h -> 10 mg q6h

 • Cytoreductive: hydroxycarbamide 500 mg QD until normal WBC

 • Continue ATRA unless severe APLS, organ dysfuxtion, ICU, refractory to steroids

 • Supportive Care: Diuresis for fluid overload, PCC to reverse coagulopathy, RRT/IMV as needed



- Dr. Noah Rosenberg @nsrosenberg



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