Differentiation (Retinoic Acid) Syndrome in Critically Ill Cancer Patients

  • Cristina Prata AmendolaEmail author
  • Ricardo André Sales Pereira Guedes
  • Luciana Coelho Sanches
Reference work entry


In patients with acute promyelocytic leukemia, induction therapy, primarily with all-trans retinoic acid (ATRA), or arsenic trioxide (ATO), capable of inducing the differentiation of leukemic cells, may lead to the development of a syndrome of differentiation, formerly known as all-trans-retinoic acid syndrome. In this situation, patients who develop the severe form present a high morbimortality rate. The diagnosis requires a high degree of suspicion, and the criteria used are clinical. Originally, the diagnostic criteria were established by Frankel et al. (Ann Intern Med 117(4):292–296, 1992) who were based on seven clinical findings: fever, weight gain (from capillary leak and soft tissue edema, secondary a storm of cytokines), respiratory distress, radiographic opacities, pleural or pericardial effusion, hypotension, and renal failure (usually from hypotension, although disseminated intravascular coagulation may also be present). In this scenario, the use of corticosteroids against suspicion promotes a significant decrease in the mortality rate, changing the prognosis and therefore the course of the disease.


Differentiation syndrome All-trans-retinoic acid syndrome Acute promyelocytic leukemia Differentiation therapy Tretinoin 


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Cristina Prata Amendola
    • 1
    Email author
  • Ricardo André Sales Pereira Guedes
    • 1
  • Luciana Coelho Sanches
    • 1
  1. 1.Fundação Pio XII – Hospital de Câncer de BarretosBarretosBrazil

Section editors and affiliations

  • Yenny Cardenas
    • 1
  1. 1.Critical Care DepartmentUniversidad del Rosario Hospital Universitario Fundacion Santa Fe deBogotaColombia

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