Indications

• Acute Promyelocytic Leukemia (APML) (see Acute Myeloid Leukemia, [[Acute Myeloid Leukemia]])

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Pharmacology

• Binds to Retinoic Acid Receptor-Promyelocytic Leukemia Complex (RAR-PML) Protein
  • Promotes differentiation of myeloid precursors and stimulates maturation of leukemic cells
  • Decreases disseminated Intravascular coagulation (DIC) and hemorrhagic complications during APML treatment
• Toxicity: probably due to cytokine release by leukemic cells or enhanced integrin expression on maturing granuloctyes (ATRA causes in vivo maturation of leukemic cells into more normal appearing granulocytes) causing adherence to vascular endothelium and migration into tissues

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Administration

• xxx

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Adverse Effects

Cardiac Adverse Effects

• Pericardial Effusion (see Pericardial Effusion, [[Pericardial Effusion]])
• Episodic Hypotension (see Hypotension, [[Hypotension]])

Pulmonary Adverse Effects

Retinoic Acid Syndrome

• Epidemiology
  • Occurs only following ATRA therapy for APML (but does not occur in patients treated with ATRA for non-hematologic cancers)
  • Occurs in 25% of ATRA-treated APML patients
  • Usually develops between days 2-21 of therapy
• Diagnosis
  • ABG: hypoxemia
  • CBC: leukocytosis may be seen
  • Bronchoscopy with Bronchoalveolar Lavage (BAL): myeloid cells and blasts may be seen
  • Thoracoscopic/Open Lung Biopsy: interstitial infiltration with maturing myeloid cells
• Clinical Patterns
  • Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]])
  • Interstitial Pneumonitis (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]])
  • Lung Nodules/Nodular Infiltrates (see Lung Nodule or Mass, [[Lung Nodule or Mass]])
  • Pleural Effusions (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])
  • Pneumonia/Alveolar Infiltrates (see Pneumonia, [[Pneumonia]])
• Treatment
  • Corticosteroids (see Corticosteroids, [[Corticosteroids]]): indicated
    • Dexamethasone 10 mg BID x 10 days -> reverses many cases
• Prognosis
  • Mortality Rate: 9%
  • Need for intubation predicts high mortality
• Prophylaxis
  • Prednisone PO Prophylaxis: when administered during ATRA therapy, decreases the incidence of pulmonary toxicity to 10% of cases

Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])

• Diagnosis
  • Bland alveolar hemorrhage (no capillaritis)
  • Elevated ANCA may be seen

Renal Adverse Effects

• Acute Kidney Injury (AKI) (see Acute Kidney Injury, [[Acute Kidney Injury]])
• Glomerulonephritis (see Acute Glomerulonephritis, [[Acute Glomerulonephritis]])

Other Adverse Effects

• Fever (see Fever, [[Fever]])
• Peripheral Edema (see Lower Extremity Edema, [[Lower Extremity Edema]])
• Weight Gain
• Sweet’s Syndrome (see Sweet’s Syndrome, [[Sweets Syndrome]])

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References

• The retinoic acid syndrome in acute promyelocytic leukemia. Ann Intern Med 1992; 117:292-296
• New chemotherapy-induced pulmonary syndromes. Pulmonary Perspectives. Northbrook, IL: American College of Chest Physicians, 1995; 12(4):4-5
• All-trans retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997; 337:1021-1025