Differentiation Syndrome (DS)1

Clinical Presentation
  • Dyspnea
  • Fever
  • Peripheral edema
  • Hypotension
  • Weight gain
  • Pleuro-pericardial effusion
  • Acute renal failure
  • Musculoskeletal pain
  • Hyperbilirubinemia

DS is a potentially fatal complication of treatment with differentiating agents. It is caused by a rapid proliferation and differentiation of myeloid precursor cells, which in turn triggers a rapid release of inflammatory cytokines that can lead to a variety of symptoms.

  • The severity of DS correlates with the number of clinical features present:
    • Severe: ≥4 clinical features
    • Moderate: 3 clinical features
    • Indeterminate: 1 to 2 clinical features
  • Less commonly, DS may be associated with pulmonary hemorrhage or acute febrile neutrophilic dermatosis
  • Patients are often treated with corticosteroids

Reference: 1. Larson RA, Bag R. Differentiation syndrome associated with treatment of acute leukemia. UpToDate website. https://www.uptodate.com/contents/differentiation-syndrome-associated-with-treatment-of-acute-leukemia. Updated July 2, 2019. Accessed April 22, 2021.