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Differentiation (Retinoic Acid) Syndrome in Critically Ill Cancer Patients

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

Abstract

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.

Keywords

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

References

  1. 1.
    Botton S, Dombret H, Sanz M, San Miguel J, Caillot D, Zittoun R, Gardembas M, Stamatoulas A, Conde E, Guerci A, Gardin C, Geiser K, Cony Makhoul D, Reman O, de la Serna J, Lefrere F, Chomienne C, Chastang C, Degos L, Fenaux P. Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1998;92:2712–8.PubMedGoogle Scholar
  2. 2.
    Breccia M, Latagliata R, Carmosino I, Cannella L, Diverio D, Guarini A, De Propris MS, Petti MC, Avvisati G, Cimino G, Mandelli F, Lo-Coco F. Clinical and biological features of acute promyelocytic leukemia patients developing retinoic acid syndrome during induction treatment with all-trans retinoic acid and idarubicin. Haematologica. 2008;93:1918–20.CrossRefGoogle Scholar
  3. 3.
    Breccia M, Mazzarella L, Bagnardi V, et al. Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols. Blood. 2012;119:49.CrossRefGoogle Scholar
  4. 4.
    Cardinale L, Asteggiano F, Moretti F, Torre F, Ulisciani S, Fava C, Rege-Cambrin G. Pathophysiology, clinical features and radiological findings of differentiation syndrome/all-trans-retinoic acid syndrome. World J Radiol. 2014;6(8):583–8.CrossRefGoogle Scholar
  5. 5.
    Choi MH, Jung JI, Do Chung W, Kim Y-J, Lee S-E, Han DH, Ahn MI, Park SH. Acute pulmonary complications in patients with hematologic malignancies. Radiographics. 2014;34(6):1755–68.CrossRefGoogle Scholar
  6. 6.
    Collinge E, Tigaud I, Balme B, Gerland LM, Sujobert P, Carlioz V, Salles G, Thomas X, Paubelle E. Case report: purulent transformation of granulocytic sarcoma: an unusual pattern of differentiation in acute promyelocyticleukemia. Medicine (Baltimore). 2018;97(8):e9657.CrossRefGoogle Scholar
  7. 7.
    De Santis GC, Madeira MI, de Oliveira LC, Falcao RP, Rego EM. Cardiac stunning as a manifestation of ATRA differentiation syndrome in acute promyelocytic leukemia. Med Oncol. 2012;29(1):248–50.CrossRefGoogle Scholar
  8. 8.
    De D, Nath UK, Chakrabarti P. Pancreatitis in acute promyelocytic leukemia: drug-induced or differentiation syndrome? Indian J Med Paediatr Oncol. 2017;38(3):371–3.CrossRefGoogle Scholar
  9. 9.
    Dos Santos GA, Kats L, Pandolfi PP. Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia. J Exp Med. 2003;210(13):2793–802.CrossRefGoogle Scholar
  10. 10.
    Dubois C, Schlageter MH, de Gentile A, et al. Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells. Blood. 1994;83(11):3264–70.PubMedGoogle Scholar
  11. 11.
    Farboud B, Hauksdottir H, Wu Y, Privalsky ML. Isotype-restricted corepressor recruitment: a constitutively closed helix 12 conformation in retinoic acid receptors beta and gamma interferes with corepressor recruitment and prevents transcriptional repression. Mol Cell Biol. 2003;23:2844–58.CrossRefGoogle Scholar
  12. 12.
    Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell RP Jr. The “retinoic acid syndrome” in acute promyelocytic leukemia. Ann Intern Med. 1992;117(4):292–6.CrossRefGoogle Scholar
  13. 13.
    Gordon M, Jakubowski A, Frankel S, et al. Neutrophil (PMN) function in patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) (abstract). Proc Annu Meet Am Soc Clin Oncol. 1991;10:A761.Google Scholar
  14. 14.
    Hickstein DD, Hickey MJ, Collins SJ. Transcriptional regulation of the leukocyte adherence protein beta subunit during human myeloid cell differentiation. J Biol Chem. 1988;263:13863.PubMedGoogle Scholar
  15. 15.
    Jeddi R, Kacem K, Ben Neji H, et al. Predictive factors of all-trans-retinoic acid related complications during induction therapy for acute promyelocyticleukemia. Hematology. 2008;13:142.CrossRefGoogle Scholar
  16. 16.
    Jeddi R, Ghédira H, Mnif S, et al. High body mass index is an independent predictor of differentiation syndrome in patients with acute promyelocytic leukemia. Leuk Res. 2010;34:545.CrossRefGoogle Scholar
  17. 17.
    Jung JI, Choi JE, Hahn ST, Min CK, Kim CC, Park SH. Radiologic features of all-trans-retinoic acid syndrome. AJR. 2002;178:475–80.CrossRefGoogle Scholar
  18. 18.
    Larson RS, Brown DC, Sklar LA. Retinoic acid induces aggregation of the acute promyelocytic leukemia cell line NB-4 by utilization of LFA-1 and ICAM-2. Blood. 1997;90:2747.CrossRefGoogle Scholar
  19. 19.
    Luesink M, Jansen JH. Advances in understanding the pulmonary infiltration in acute promyelocyticleukaemia. Br J Haematol. 2010;151: 209–20.CrossRefGoogle Scholar
  20. 20.
    Luesink M, Pennings JL, Wissink WM, Linssen PC, Muus P, Pfundt R, de Witte TJ, van der Reijden BA, Jansen JH. Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome. Blood. 2009;114(27):5512.CrossRefGoogle Scholar
  21. 21.
    Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Ber- nasconi C, Broccia G, Cerri R, Falda M, Fioritoni G, Leoni F, Liso V, Petti MC, Rodeghiero F, Saglio G, Vegna ML, Visani G, Jehn U, Willemze R, Muus P, Pelicci PG, Biondi A, Lo-Coco F. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-MalattieEmatologiche Maligne dell’AdultoandAssociazione Italiana di E- matologiaed Oncologia Pediatrica Cooperative Groups. Blood. 1997;90:1014–21.PubMedGoogle Scholar
  22. 22.
    Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. (Overview). Cell. 1995;83:835–9.CrossRefGoogle Scholar
  23. 23.
    McGregor A, Hurst E, Lord S, Jones G. Bradycardiafollowing retinoic acid differentiation syndrome in a patient with acute promyelocyticleukaemia. BMJ Case Rep. 2012;9:2012.Google Scholar
  24. 24.
    Melnick A, Licht JD. Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood. 1999;93:3167–215.CrossRefGoogle Scholar
  25. 25.
    Montesinos P, Bergua JM, Vellenga E, Rayon C, Parody R, de la Serna J, Leon A, Esteve J, Milone G, Deben G, Rivas C, Gonzalez M, Tormo M, Diaz-Mediavilla J, Gonzalez JD, Negri S, Amutio E, Brunet S, Lowenberg B, Sanz MA. Differentiation syndrome in patients with acute promyelocyticleukemia treated with all-transretinoic acid and anthracycline chemotherapy: characteristics, outcome and prognostic factors. Blood. 2008;113:775–83.CrossRefGoogle Scholar
  26. 26.
    Montesinos P, Bergua JM, Vellenga E, CheloRayon RP, de laSerna J, Leon A, Esteve J, Milone G, Deben G, Rivas C, Gonzalez M, Tormo M, Díaz-Mediavilla J, Gonzalez JD, Negri S, Amutio E, Brunet S, Lowenberg B, Sanz MA. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors. Blood. 2009;113(4):775–83.CrossRefGoogle Scholar
  27. 27.
    Nasr R, ValérieLallemand-Breitenbach JZ, Guillemin M-C, de Thé H. Therapy-induced PML/RARA proteolysis and acute promyelocytic leukemia cure. Clin Cancer Res. 2009;15(20):6321–6.CrossRefGoogle Scholar
  28. 28.
    National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. Acute Myeloid Leuk Version 1.2018 – Feb 7Google Scholar
  29. 29.
    Newman AR, Leung B, Richards A, Campbell TG, Wellwood J, Imrie FR. Two cases of differentiation syndrome with ocular manifestations in patients with acute promyelocyticleukaemia treated with all-trans retinoic acid and arsenic trioxide. Am J Ophthalmol Case Rep. 2018;9:106–11.CrossRefGoogle Scholar
  30. 30.
    Raanani P, Segal E, Levi I, Bercowicz M, Berkenstat H, Avigdor A, Perel A, Ben-Bassat I. Diffuse alveolar hemorrhage in acute promyelocytic leukemia patients treated with ATRA–a manifestation of the basic disease or the treatment. Leuk Lymphoma. 2000;37(5–6):605.CrossRefGoogle Scholar
  31. 31.
    Santos FL, Dore AI, Lima AS, et al. Hematological features and expression profile of myeloid antigens of acute promyelocytic leukemia patients: analysis of prognostic factors for development of the retinoic acid syndrome. Rev Assoc Med Bras (1992). 2004;50:286.CrossRefGoogle Scholar
  32. 32.
    Sanz MA, Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. Blood. 2014;123(18):2777–82.CrossRefGoogle Scholar
  33. 33.
    Sanz MA, Grimwade D, Tallman MS, Lowenberg B, Fenaux P, Estey EH, Naoe T, Lengfelder E, Büchner T, Döhner H, Burnett AK, Lo-Coco F. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European Leukemia Net. Blood. 2009;113(9):1875.CrossRefGoogle Scholar
  34. 34.
    Seale J, Delva L, Renesto P, et al. All-trans retinoic acid rapidly decreases cathepsin G synthesis and mRNA expression in acute promyelocytic leukemia. Leukemia. 1996;10(1):95–101.PubMedGoogle Scholar
  35. 35.
    Siddall E, Khatri M, Radhakrishnan J. Capillary leak syndrome: etiologies, pathophysiology, and management. Kidney Int. 2017;92:37–46.CrossRefGoogle Scholar
  36. 36.
    Solano-López G, Llamas-Velasco M, Concha-Garzón MJ, Daudén E. Sweet syndrome and differentiation syndrome in a patient with acute promyelocytic leukemia. World J Clin Cases. 2015;3(2):196–8.CrossRefGoogle Scholar

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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