Retinoic acid syndrome
Background
- Differentiation syndrome (DS) is most current term
- Occurs in Acute promyelocytic leukemia patients undergoing ATRA treatment (Tretinoin, Vesanoid)
- And/or with arsenic trioxide therapy (Trisenox, ATO)
- Chemo treatment differentiates APML blasts into mature granulocytes
- Differentiation of blasts may cause sepsis-like "cytokine storm" leading to tissue damage
- Incidence of DS[1]
- Up to 25% of patients undergoing ATRA
- Up to 31% of patients undergoing ATO
- Up to 40% mortality in patients requiring mechanical ventilation
- Diagnosis made clinically with symptomology
- Requires immediate treatment with steroids
- Steroids highly recommended even if other diagnoses possible
Clinical Features
- Unexplained fever
- Unexplained hypotension
- Weight gain > 5 kg
- Dyspnea with pulmonary infiltrates
- Pericardial effusion
- Pleural effusion
- Renal failure
- Vascular capillary leak syndrome
- DIC
- Never observed beyond induction therapy, when patient has achieved complete response
Differential Diagnosis
Related to Local Tumor Effects
- Malignant airway obstruction
- Bone metastases and pathologic fractures
- Malignant spinal cord compression
- Malignant Pericardial Effusion and Tamponade
- Superior vena cava syndrome
Related to Biochemical Derangement
- Hypercalcemia of malignancy
- Hyponatremia due to SIADH
- Adrenal insufficiency
- Tumor lysis syndrome
- Carcinoid syndrome
Related to Hematologic Derangement
Related to Therapy
- Chemotherapy-induced nausea and vomiting
- Cytokine release syndrome
- Chemotherapeutic drug extravasation
- Differentiation syndrome (retinoic acid syndrome) in APML
- Stem cell transplant complications
- Catheter-related complications
- Tunnel infection
- Exit site infection
- CVC obstruction (intraluminal or catheter tip thrombosis)
- Catheter-related venous thrombosis
- Fracture of catheter lumen
- Oncologic therapy related adverse events
Evaluation
- Ultimately, a clinical diagnosis
- Troponins for pericarditis
- Severe leukocytosis on CBC
- Sepsis workup
- CHF workup, echo
- Pulmonary embolism workup
- DIC workup
- Coagulation factor levels
- Diagnostic bronchoscopy, BAL, biopsy usually not required
- Imaging
- CXR - pleural effusions, ground-glass opacities, increased cardiac silhouette
- CT chest - pleural effusions, peripheral nodules
Management[2]
- Dexamethasone 10mg IV q12hrs
- Most important therapy, with possible dramatic and rapid resolution of symptoms
- Continue treatment until complete disappearance of signs and symptoms
- Temporary discharge ATRA or ATO only in severe cases of DS (renal failure or ICU admit)
- Supportive
- Mechanical ventilation for respiratory failure
- Careful IVF admin, prioritizing blood products for coagulopathies (DIC)
- Furosemide for fluid overload
- CRRT/HD for refractory renal failure
- Vasopressors
- Empiric antibiotics
- Avoid invasive pleural/pericardial effusion diagnostics
Disposition
- Admit
See Also
External Links
References
- Montesinos P and Sanz MA. The Differentiation Syndrome in Patients with Acute Promyelocytic Leukemia: Experience of the Pethema Group and Review of the Literature. Mediterr J Hematol Infect Dis. 2011; 3(1): e2011059.
- Sanz MA and Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. May 1, 2014; Blood: 123 (18).
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