Advertisement

Diagnosis and Treatment-Related Complications of Acute Leukemia

  • Lauren PommertEmail author
  • Steven Margossian
  • Michael Burke
Chapter

Abstract

Children diagnosed with acute leukemia are challenged not only by the life-threatening disease itself but a myriad of potential lethal complications related to treatment, some of which can result in end-organ dysfunction requiring pediatric intensive care unit (PICU) management. Such complications of leukemia treatment and/or the disease itself range from hyperleukocytosis and tumor lysis syndrome to typhlitis, pancreatitis, and serious coagulopathies. It is important that healthcare providers caring for children and adolescent patients with acute leukemia can recognize these potential complications in order to appropriately triage and manage them. As the overall survival for children with acute leukemia continues to improve, research has focused on novel strategies to further decrease the burden of therapy and lower the rates of toxic death while maintaining these very good outcomes. This chapter provides an overview of some of the more common oncologic emergencies occurring in children with acute leukemia that may require PICU care, focusing on the diagnosis and management.

Keywords

Tumor lysis syndrome Hyperleukocytosis and leukostasis Mediastinal masses Superior vena cava syndrome CNS emergencies Thrombosis Typhlitis Pancreatitis Acute promyelocytic leukemia Differentiation syndrome 

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRefGoogle Scholar
  2. 2.
    Ward E, DeSantis C, Robbins A, Kohler B, Jemal A. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin. 2014;64(2):83–103. https://doi.org/10.3322/caac.21219.Google Scholar
  3. 3.
    Pui CH, et al. Childhood acute lymphoblastic leukemia: progress through collaboration. J Clin Oncol. 2015;33(27):2938–48.CrossRefGoogle Scholar
  4. 4.
    Gamis AS, et al. Children’s Oncology Group’s 2013 blueprint for research: acute myeloid leukemia. Pediatr Blood Cancer. 2013;60(6):964–71.CrossRefGoogle Scholar
  5. 5.
    Stary J, Hrusak O. Recent advances in the management of pediatric acute lymphoblastic leukemia. F1000Res. 2016;5:2635.CrossRefGoogle Scholar
  6. 6.
    Freedman JL, Rheingold SR, Fisher MJ. Oncologic emergencies. In: Pizzo P, Poplack D, editors. Principles and practice of pediatric oncology. Philadelphia: Wolters Kluwer; 2016. p. 967–91.Google Scholar
  7. 7.
    Lund B, et al. Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia. Pediatr Blood Cancer. 2011;56(4):551–9.CrossRefGoogle Scholar
  8. 8.
    Coiffier B, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol. 2008;26(16):2767–78.CrossRefGoogle Scholar
  9. 9.
    Cairo MS, Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol. 2004;127(1):3–11.CrossRefGoogle Scholar
  10. 10.
    Annemans L, et al. Incidence, medical resource utilisation and costs of hyperuricemia and tumour lysis syndrome in patients with acute leukaemia and non-Hodgkin’s lymphoma in four European countries. Leuk Lymphoma. 2003;44(1):77–83.CrossRefGoogle Scholar
  11. 11.
    Cairo MS, et al. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149(4):578–86.CrossRefGoogle Scholar
  12. 12.
    Wilson FP, Berns JS. Onco-nephrology: tumor lysis syndrome. Clin J Am Soc Nephrol. 2012;7(10):1730–9.CrossRefGoogle Scholar
  13. 13.
    Cairo MS, et al. A clinical and economic comparison of rasburicase and allopurinol in the treatment of patients with clinical or laboratory tumor lysis syndrome. Clin Lymphoma Myeloma Leuk. 2017;17(3):173–8.CrossRefGoogle Scholar
  14. 14.
    Smalley RV, et al. Allopurinol: intravenous use for prevention and treatment of hyperuricemia. J Clin Oncol. 2000;18(8):1758–63.CrossRefGoogle Scholar
  15. 15.
    Jeha S, et al. Efficacy and safety of rasburicase, a recombinant urate oxidase (Elitek), in the management of malignancy-associated hyperuricemia in pediatric and adult patients: final results of a multicenter compassionate use trial. Leukemia. 2005;19(1):34–8.CrossRefGoogle Scholar
  16. 16.
    Goldman SC, et al. A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood. 2001;97(10):2998–3003.CrossRefGoogle Scholar
  17. 17.
    Kikuchi A, et al. A study of rasburicase for the management of hyperuricemia in pediatric patients with newly diagnosed hematologic malignancies at high risk for tumor lysis syndrome. Int J Hematol. 2009;90(4):492–500.CrossRefGoogle Scholar
  18. 18.
    Wilson FP, Berns JS. Tumor lysis syndrome: new challenges and recent advances. Adv Chronic Kidney Dis. 2014;21(1):18–26.CrossRefGoogle Scholar
  19. 19.
    Agha-Razii M, et al. Continuous veno-venous hemodiafiltration for the treatment of spontaneous tumor lysis syndrome complicated by acute renal failure and severe hyperuricemia. Clin Nephrol. 2000;54(1):59–63.PubMedGoogle Scholar
  20. 20.
    Porcu P, et al. Hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management. Leuk Lymphoma. 2000;39(1–2):1–18.CrossRefGoogle Scholar
  21. 21.
    Lowe EJ, et al. Early complications in children with acute lymphoblastic leukemia presenting with hyperleukocytosis. Pediatr Blood Cancer. 2005;45(1):10–5.CrossRefGoogle Scholar
  22. 22.
    Ganzel C, et al. Hyperleukocytosis, leukostasis and leukapheresis: practice management. Blood Rev. 2012;26(3):117–22.CrossRefGoogle Scholar
  23. 23.
    Abla O, et al. Early complications of hyperleukocytosis and leukapheresis in childhood acute leukemias. J Pediatr Hematol Oncol. 2016;38(2):111–7.CrossRefGoogle Scholar
  24. 24.
    Nguyen R, et al. The role of leukapheresis in the current management of hyperleukocytosis in newly diagnosed childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2016;63(9):1546–51.CrossRefGoogle Scholar
  25. 25.
    Sung L, et al. Predictors and short-term outcomes of hyperleukocytosis in children with acute myeloid leukemia: a report from the Children’s Oncology Group. Haematologica. 2012;97(11):1770–2.CrossRefGoogle Scholar
  26. 26.
    Nowacki P, et al. Co-existence of thrombocytopenia and hyperleukocytosis (‘critical period’) as a risk factor of haemorrhage into the central nervous system in patients with acute leukaemias. Haematologia (Budap). 2002;31(4):347–55.CrossRefGoogle Scholar
  27. 27.
    Attarbaschi A, et al. Mediastinal mass in childhood T-cell acute lymphoblastic leukemia: significance and therapy response. Med Pediatr Oncol. 2002;39(6):558–65.CrossRefGoogle Scholar
  28. 28.
    Pearson JK, Tan GM. Pediatric anterior mediastinal mass: a review article. Semin Cardiothorac Vasc Anesth. 2015;19(3):248–54.CrossRefGoogle Scholar
  29. 29.
    Wilson LD, Detterbeck FC, Yahalom J. Clinical practice. Superior vena cava syndrome with malignant causes. N Engl J Med. 2007;356(18):1862–9.CrossRefGoogle Scholar
  30. 30.
    Acker SN, et al. A multidisciplinary approach to the management of anterior mediastinal masses in children. J Pediatr Surg. 2015;50(5):875–8.CrossRefGoogle Scholar
  31. 31.
    Anghelescu DL, et al. Clinical and diagnostic imaging findings predict anesthetic complications in children presenting with malignant mediastinal masses. Paediatr Anaesth. 2007;17(11):1090–8.PubMedPubMedCentralGoogle Scholar
  32. 32.
    McCurdy MT, Shanholtz CB. Oncologic emergencies. Crit Care Med. 2012;40(7):2212–22.CrossRefGoogle Scholar
  33. 33.
    Perger L, Lee EY, Shamberger RC. Management of children and adolescents with a critical airway due to compression by an anterior mediastinal mass. J Pediatr Surg. 2008;43(11):1990–7.CrossRefGoogle Scholar
  34. 34.
    Garey CL, et al. Management of anterior mediastinal masses in children. Eur J Pediatr Surg. 2011;21(5):310–3.CrossRefGoogle Scholar
  35. 35.
    Ng A, et al. Anaesthetic outcome and predictive risk factors in children with mediastinal tumours. Pediatr Blood Cancer. 2007;48(2):160–4.CrossRefGoogle Scholar
  36. 36.
    Hack HA, Wright NB, Wynn RF. The anaesthetic management of children with anterior mediastinal masses. Anaesthesia. 2008;63(8):837–46.CrossRefGoogle Scholar
  37. 37.
    Frey TK, et al. A child with anterior mediastinal mass supported with veno-arterial extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2006;7(5):479–81.CrossRefGoogle Scholar
  38. 38.
    Vagace JM, et al. Central nervous system chemotoxicity during treatment of pediatric acute lymphoblastic leukemia/lymphoma. Crit Rev Oncol Hematol. 2012;84(2):274–86.CrossRefGoogle Scholar
  39. 39.
    Bhojwani D, et al. Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia. J Clin Oncol. 2014;32(9):949–59.CrossRefGoogle Scholar
  40. 40.
    Zwaan CM, et al. Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study. Br J Haematol. 2017;179(2):284–93.CrossRefGoogle Scholar
  41. 41.
    Berg SL, et al. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children’s Oncology Group. J Clin Oncol. 2005;23(15):3376–82.CrossRefGoogle Scholar
  42. 42.
    Dunsmore KP, et al. Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia: a report from the Children’s Oncology Group. J Clin Oncol. 2012;30(22):2753–9.CrossRefGoogle Scholar
  43. 43.
    Tang JH, et al. Study of posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia after induction chemotherapy. J Child Neurol. 2016;31(3):279–84.CrossRefGoogle Scholar
  44. 44.
    Kwon S, Koo J, Lee S. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Pediatr Neurol. 2001;24(5):361–4.CrossRefGoogle Scholar
  45. 45.
    Meltzer JA, Jubinsky PT. Acute myeloid leukemia presenting as spinal cord compression. Pediatr Emerg Care. 2005;21(10):670–2.CrossRefGoogle Scholar
  46. 46.
    Isome K, et al. Spinal cord compression by epidural involvement over 21 vertebral levels in acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2011;33(2):153–7.CrossRefGoogle Scholar
  47. 47.
    Mantadakis E, et al. Spinal cord compression in an adolescent with relapsed B-precursor acute lymphoblastic leukemia and mental neuropathy. Int J Hematol. 2008;88(3):294–8.CrossRefGoogle Scholar
  48. 48.
    van Veen JJ, Nokes TJ, Makris M. The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals. Br J Haematol. 2010;148(1):15–25.CrossRefGoogle Scholar
  49. 49.
    Caruso V, et al. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood. 2006;108(7):2216–22.CrossRefGoogle Scholar
  50. 50.
    Grace RF, et al. The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute consortium protocols. Br J Haematol. 2011;152(4):452–9.CrossRefGoogle Scholar
  51. 51.
    Qureshi A, et al. Asparaginase-related venous thrombosis in UKALL 2003- re-exposure to asparaginase is feasible and safe. Br J Haematol. 2010;149(3):410–3.CrossRefGoogle Scholar
  52. 52.
    Appel IM, et al. Influence of two different regimens of concomitant treatment with asparaginase and dexamethasone on hemostasis in childhood acute lymphoblastic leukemia. Leukemia. 2007;21(11):2377–80.CrossRefGoogle Scholar
  53. 53.
    Hunault-Berger M, et al. Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study. Haematologica. 2008;93(10):1488–94.CrossRefGoogle Scholar
  54. 54.
    Monagle P, et al. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e737S–801S.CrossRefGoogle Scholar
  55. 55.
    Shafey A, et al. Incidence, risk factors, and outcomes of enteritis, typhlitis, and colitis in children with acute leukemia. J Pediatr Hematol Oncol. 2013;35(7):514–7.CrossRefGoogle Scholar
  56. 56.
    Mullassery D, et al. Diagnosis, incidence, and outcomes of suspected typhlitis in oncology patients – experience in a tertiary pediatric surgical center in the United Kingdom. J Pediatr Surg. 2009;44(2):381–5.CrossRefGoogle Scholar
  57. 57.
    Altinel E, et al. Typhlitis in acute childhood leukemia. Med Princ Pract. 2012;21(1):36–9.CrossRefGoogle Scholar
  58. 58.
    Gray TL, et al. Gastrointestinal complications in children with acute myeloid leukemia. Leuk Lymphoma. 2010;51(5):768–77.CrossRefGoogle Scholar
  59. 59.
    Fike FB, et al. Neutropenic colitis in children. J Surg Res. 2011;170(1):73–6.CrossRefGoogle Scholar
  60. 60.
    McCarville MB, et al. Typhlitis in childhood cancer. Cancer. 2005;104(2):380–7.CrossRefGoogle Scholar
  61. 61.
    Hijiya N, van der Sluis IM. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk Lymphoma. 2016;57(4):748–57.CrossRefGoogle Scholar
  62. 62.
    Wolthers BO, et al. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study. Lancet Oncol. 2017;18(9):1238–48.CrossRefGoogle Scholar
  63. 63.
    Oparaji JA, et al. Risk factors for Asparaginase-associated pancreatitis: a systematic review. J Clin Gastroenterol. 2017;51(10):907–13.CrossRefGoogle Scholar
  64. 64.
    Schmiegelow K, et al. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy. F1000Res. 2017;6:444.CrossRefGoogle Scholar
  65. 65.
    Silverman LB, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood. 2001;97(5):1211–8.CrossRefGoogle Scholar
  66. 66.
    Pession A, et al. Long-term results of a randomized trial on extended use of high dose L-asparaginase for standard risk childhood acute lymphoblastic leukemia. J Clin Oncol. 2005;23(28):7161–7.CrossRefGoogle Scholar
  67. 67.
    Stein EM, Tallman MS. Acute promyelocytic leukemia in children and adolescents. Acta Haematol. 2014;132(3–4):307–12.CrossRefGoogle Scholar
  68. 68.
    Gregory J, Feusner J. Acute promyelocytic leukemia in childhood. Curr Oncol Rep. 2009;11(6):439–45.CrossRefGoogle Scholar
  69. 69.
    Sanz MA, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113(9):1875–91.CrossRefGoogle Scholar
  70. 70.
    Kutny MA, Gregory J Jr, Feusner JH. Treatment of paediatric APL: how does the therapeutic approach differ from adults? Best Pract Res Clin Haematol. 2014;27(1):69–78.CrossRefGoogle Scholar
  71. 71.
    Fisher BT, et al. Induction mortality, ATRA administration, and resource utilization in a nationally representative cohort of children with acute promyelocytic leukemia in the United States from 1999 to 2009. Pediatr Blood Cancer. 2014;61(1):68–73.CrossRefGoogle Scholar
  72. 72.
    Testi AM, et al. GIMEMA-AIEOPAIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children. Blood. 2005;106(2):447–53.CrossRefGoogle Scholar
  73. 73.
    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

Copyright information

© Springer International Publishing 2019

Authors and Affiliations

  • Lauren Pommert
    • 1
    Email author
  • Steven Margossian
    • 2
  • Michael Burke
    • 1
  1. 1.Division of Hematology/Oncology/Blood and Marrow Transplant, Department of PediatricsMedical College of Wisconsin and Children’s Hospital of WisconsinMilwaukeeUSA
  2. 2.Harvard Medical School, Department of Pediatric OncologyDana Farber Cancer Institute, Boston Children’s HospitalBostonUSA

Personalised recommendations