Acute promyelocytic leukemia natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Overview

The natural history of acute promyelocytic leukemia is characterized by symptoms related to defective normal blood cell production. These symptoms include fatigue, bleeding, and infection. Complications include thrombosis and hemorrhage, which eventually occur in a significant proportion of patients. Early death is common and is related to bleeding complications. Therapy-related complications include differentiation syndrome, QT interval prolongation, and cardiomyopathy. The prognosis of acute promyelocytic leukemia was previously poor, but the advent of arsenic trioxide and all-trans retinoic acid has rendered the prognosis to be far more favorable in the recent years.

Natural History

Complications

In a 2015 study from MD Anderson Cancer Center, it was shown that the annual incidence of venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, was 6.1-42%, which is the highest amongst all leukemia sub-types. In contrast, the incidence of venous thromboembolism in chronic myeloid leukemia was only 1.5%.[7]

Disease Thrombotic Incidence

Acute promyelocytic leukemia

6.1-48%

Acute myeloid leukemia

3.7%

Chronic lymphocytic leukemia

2.7%

Acute lymphoblastic leukemia

2.1-13%

Chronic myeloid leukemia

1.5%

Prognosis

  • Prior to the introduction of readily available diagnostics and targeted therapeutics, the prognosis of acute promyelocytic leukemia was previously very poor, especially in the early phase of the disease.[31][32]
  • The poor prognosis was due to high bleeding risk and death from hemorrhagic complications due to disseminated intravascular coagulation. Death typically occurs within a few days to weeks in the absence of treatment. The early death rate is estimated to be 17.3%, based on a large population-based analysis that was conducted in the United Stated between 1992-2007.[33] [2]
  • The 5-year survival rate is only 30-40% after 5 years in younger patients.[23] In the current era of medicine (after the introduction of all-trans retinoic acid and arsenic trioxide), the prognosis of acute promyelocytic leukemia carries a much better prognosis.[3]
  • Patients can achieve long-term, durable remission if treated appropriately in an expedited manner with medications such as all-''trans'' retinoic acid, arsenic trioxide, or cytotoxic chemotherapy. The current overall survival rate is 86-97%, and the complete remission rate is 90-100%.[23]
  • In a multi-center study published in 2017 that evaluated the long-term outcomes of patients with acute promyelocytic leukemia, the complete remission rate was 96% [34] and induction mortality if low at 4%.[34]

References

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  2. 2.0 2.1 Chen C, Huang X, Wang K, Chen K, Gao D, Qian S (2018). "Early mortality in acute promyelocytic leukemia: Potential predictors". Oncol Lett. 15 (4): 4061–4069. doi:10.3892/ol.2018.7854. PMC 5835847. PMID 29541170.
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  4. 4.0 4.1 Choudhry, Aditi; DeLoughery, Thomas G. (2012). "Bleeding and thrombosis in acute promyelocytic leukemia". American Journal of Hematology. 87 (6): 596–603. doi:10.1002/ajh.23158. ISSN 0361-8609.
  5. Choudhry, Aditi; DeLoughery, Thomas G. (2012). "Bleeding and thrombosis in acute promyelocytic leukemia". American Journal of Hematology. 87 (6): 596–603. doi:10.1002/ajh.23158. ISSN 0361-8609.
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  8. Al-Ani, F., Ahrari, A., Wang, Y. P., Iansavitchene, A., & Lazo-Langner, A. (2017). Incidence of Venous Thromboembolism in Acute Leukemia: A Systematic Review and Meta-Analysis. Blood, 130(Suppl 1), 5634. Accessed January 15, 2019. Retrieved from http://www.bloodjournal.org/content/130/Suppl_1/5634.
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  11. . doi:10.1182/blood-2016-09-739334 PMCID: PMC5374289 Check |doi= value (help). Missing or empty |title= (help)
  12. Periayah MH, Halim AS, Mat Saad AZ (October 2017). "Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in Hemostasis". Int J Hematol Oncol Stem Cell Res. 11 (4): 319–327. PMC 5767294. PMID 29340130.
  13. Flores, Brisas; D Trivedi, Hirsh; C Robson, Simon; Bonder, Alan (2017). "Hemostasis, bleeding and thrombosis in liver disease". Journal of Translational Science. 3 (3). doi:10.15761/JTS.1000182. ISSN 2059-268X.
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  16. Dally, Najib; Hoffman, Ron; Haddad, Nuhad; Sarig, Galit; Rowe, Jacob M.; Brenner, Benjamin (2005). "Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukemia—a single center experience in 34 patients". Thrombosis Research. 116 (2): 109–114. doi:10.1016/j.thromres.2004.11.001. ISSN 0049-3848.
  17. Handigund, Rajeshwari Satish; Malur, Prakash R.; Dhumale, Annasaheb J.; Bali, Akshay; Roy, Maitrayee; Inumella, Suvarna (2012). "Severe Aplastic Anemia Manifesting After Complete Remission of Acute Promyelocytic Leukemia: Is it a Fortuitous Association?". Indian Journal of Hematology and Blood Transfusion. 30 (1): 64–67. doi:10.1007/s12288-012-0201-8. ISSN 0971-4502.
  18. Bittencourt, Henrique; Teixeira Junior, Antonio Lucio; Glória, Ana Beatriz Firmato; Ribeiro, Ana Flávia Leonardi Tiburcio; Fagundes, Evandro Maranhão (2011). "Acute promyelocytic leukemia presenting as an extradural mass". Revista Brasileira de Hematologia e Hemoterapia. 33 (6): 478–480. doi:10.5581/1516-8484.20110126. ISSN 1516-8484.
  19. Fibach, Eitan; Rachmilewitz, Eliezer A. (2017). "Iron overload in hematological disorders". La Presse Médicale. 46 (12): e296–e305. doi:10.1016/j.lpm.2017.10.007. ISSN 0755-4982.
  20. Sanz, M. A.; Montesinos, P. (2014). "How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia". Blood. 123 (18): 2777–2782. doi:10.1182/blood-2013-10-512640. ISSN 0006-4971.
  21. Montesinos, Pau; Sanz, Miguel A (2011). "THE DIFFERENTIATION SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA: EXPERIENCE OF THE PETHEMA GROUP AND REVIEW OF THE LITERATURE". Mediterranean Journal of Hematology and Infectious Diseases. 3 (1): e2011059. doi:10.4084/mjhid.2011.059. ISSN 2035-3006.
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  24. Sanz, M. A.; Montesinos, P. (2014). "How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia". Blood. 123 (18): 2777–2782. doi:10.1182/blood-2013-10-512640. ISSN 0006-4971.
  25. Montesinos, Pau; Sanz, Miguel A (2011). "THE DIFFERENTIATION SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA: EXPERIENCE OF THE PETHEMA GROUP AND REVIEW OF THE LITERATURE". Mediterranean Journal of Hematology and Infectious Diseases. 3 (1): e2011059. doi:10.4084/mjhid.2011.059. ISSN 2035-3006.
  26. Porta‐Sánchez, Andreu; Gilbert, Cameron; Spears, Danna; Amir, Eitan; Chan, Joyce; Nanthakumar, Kumaraswamy; Thavendiranathan, Paaladinesh (2017). "Incidence, Diagnosis, and Management of QT Prolongation Induced by Cancer Therapies: A Systematic Review". Journal of the American Heart Association. 6 (12). doi:10.1161/JAHA.117.007724. ISSN 2047-9980.
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  28. McCulloch, Derek; Brown, Christina; Iland, Harry (2017). "Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives". OncoTargets and Therapy. Volume 10: 1585–1601. doi:10.2147/OTT.S100513. ISSN 1178-6930.
  29. McGowan, John V; Chung, Robin; Maulik, Angshuman; Piotrowska, Izabela; Walker, J Malcolm; Yellon, Derek M (2017). "Anthracycline Chemotherapy and Cardiotoxicity". Cardiovascular Drugs and Therapy. 31 (1): 63–75. doi:10.1007/s10557-016-6711-0. ISSN 0920-3206.
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  32. Efficace, Fabio; Breccia, Massimo; Avvisati, Giuseppe; Cottone, Francesco; Intermesoli, Tamara; Borlenghi, Erika; Carluccio, Paola; Rodeghiero, Francesco; Fabbiano, Francesco; Luppi, Mario; Romani, Claudio; Sborgia, Marco; D’Ardia, Stefano; Nobile, Francesco; Cantore, Nicola; Crugnola, Monica; Nadali, Gianpaolo; Vignetti, Marco; Amadori, Sergio; Lo Coco, Francesco (2018). "Health-related quality of life, symptom burden, and comorbidity in long-term survivors of acute promyelocytic leukemia". Leukemia. doi:10.1038/s41375-018-0325-4. ISSN 0887-6924.
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  34. 34.0 34.1 Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E; et al. (2017). "Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab". Blood. 129 (10): 1275–1283. doi:10.1182/blood-2016-09-736686. PMC 5413297. PMID 28003274.

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