Acute Lymphoblastic Leukemia

  • Eddy SupriyadiEmail author
  • Pudjo Hagung Widjajanto


Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, accounts for one-fourth of childhood cancers. The incidence peaks in children aged between 2 and 5 years, which is higher in boys than girls. Genetic factors, environmental factors, viral infection, and immunodeficiency have been associated with ALL. However, the cause of ALL remains unknown. ALL may be found on incidental finding on a routine blood cell count of an asymptomatic child or as a life-threatening hemorrhage or infections. The diagnosis is based on clinical findings and laboratory examinations included: leukemic lymphoblasts examination for morphologic, immunologic, cytogenetic and molecular genetics characterizations. The treatment typically consists of four phases: a remission induction, intensification, CNS prophylaxis and continuation therapy, and should be adapted on the local situation. Leukocyte count, age at diagnosis and immunophenotype are important prognostic factors.


ALL Diagnostic Treatment Prognostic 



Acute Lymphoblastic Leukemia


Acute Myeloblastic Leukemia


Deoxyribonucleic Acid


Event-Free Survival


Central Nervous System


White Blood Cell


Gastro Intestinal Tract


Lactate Dehydrogenase


Disseminated Intravascular Coagulation


French American British


World Health Organization


Cluster of Differentiation


Central Nervous System






Tumor Lysis Syndrome


  1. 1.
    Jemal A et al (2006) Cancer statistics, 2006. CA Cancer J Clin 56(2):106–130CrossRefGoogle Scholar
  2. 2.
    Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA. SEER cancer statistics review, 1975–2010. 2013 April 2013 [cited 2014 2 February]; Available from
  3. 3.
    Granfeldt Ostgard LS et al (2015) Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a national population-based cohort study. J Clin Oncol 33(31):3641–3649CrossRefGoogle Scholar
  4. 4.
    Clavel J et al (2004) Incidence of childhood leukaemia and non-Hodgkin’s lymphoma in France: national registry of childhood leukaemia and lymphoma, 1990–1999. Eur J Cancer Prev 13(2):97–103CrossRefGoogle Scholar
  5. 5.
    Smith MA, Ries LAG (2002) Childhood cancer: incidence, survival and mortality. In: Pizzo PA, Poplack DG (eds) Principles and practice of pediatric oncology. Lippincott, Williams and Wilkins, Philadelphia, pp 1–12Google Scholar
  6. 6.
    Kinlen LJ, Hudson CM, Stiller CA (1991) Contacts between adults as evidence for an infective origin of childhood leukaemia: an explanation for the excess near nuclear establishments in west Berkshire? Br J Cancer 64(3):549–554CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Alexander FE et al (1997) Clustering of childhood leukaemia in Hong Kong: association with the childhood peak and common acute lymphoblastic leukaemia and with population mixing. Br J Cancer 75(3):457–463CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Koushik A, King WD, McLaughlin JR (2001) An ecologic study of childhood leukemia and population mixing in Ontario, Canada. Cancer Causes Control 12(6):483–490CrossRefGoogle Scholar
  9. 9.
    Ceppi F et al (2009) Cytogenetic characterization of childhood acute lymphoblastic leukemia in Nicaragua. Pediatr Blood Cancer 53(7):1238–1241CrossRefGoogle Scholar
  10. 10.
    Supriyadi E et al (2011) Incidence of childhood leukemia in Yogyakarta, Indonesia, 1998–2009. Pediatr Blood Cancer 57(4):588–593CrossRefGoogle Scholar
  11. 11.
    Auvinen A et al (1994) Fallout from Chernobyl and incidence of childhood leukaemia in Finland, 1976–92. BMJ 309(6948):151–154CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bandi P et al (2006) Trends in childhood cancer incidence in Wisconsin, 1980–1999. WMJ 105(7):30–37PubMedGoogle Scholar
  13. 13.
    Barton C (2001) The incidence of childhood leukaemia in West Berkshire. Med Confl Surviv 17(1):48–55CrossRefGoogle Scholar
  14. 14.
    Bell J (1993) Trends in the incidence of childhood leukemia between 1961 and 1985 and trends in radiation exposure in parents. Health Rep 5(1):111–115PubMedGoogle Scholar
  15. 15.
    Birch JM et al (1981) Childhood leukaemia in North West England 1954–1977: epidemiology, incidence and survival. Br J Cancer 43(3):324–329CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Coebergh JW et al (2006) Leukaemia incidence and survival in children and adolescents in Europe during 1978–1997. Report from the automated childhood cancer information system project. Eur J Cancer 42(13):2019–2036CrossRefGoogle Scholar
  17. 17.
    Fajardo-Gutierrez A et al (2007) Incidence of cancer in children residing in ten jurisdictions of the Mexican Republic: importance of the Cancer registry (a population-based study). BMC Cancer 7:68CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Kroll ME et al (2006) Childhood leukemia incidence in Britain, 1974–2000: time trends and possible relation to influenza epidemics. J Natl Cancer Inst 98(6):417–420CrossRefGoogle Scholar
  19. 19.
    Mason J, Griffiths M (2012) Molecular diagnosis of leukemia. Expert Rev Mol Diagn 12(5):511–526CrossRefGoogle Scholar
  20. 20.
    Pui CH et al (2011) Improved prognosis for older adolescents with acute lymphoblastic leukemia. J Clin Oncol 29(4):386–391CrossRefGoogle Scholar
  21. 21.
    Pui CH (2010) Recent research advances in childhood acute lymphoblastic leukemia. J Formos Med Assoc 109(11):777–787CrossRefGoogle Scholar
  22. 22.
    Schultz KR et al (2009) Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children’s oncology group study. J Clin Oncol 27(31):5175–5181CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Pui CH, Robison LL, Look AT (2008) Acute lymphoblastic leukaemia. Lancet 371(9617):1030–1043CrossRefGoogle Scholar
  24. 24.
    Pizzo PA, Poplack DG (2002) In: Pizzo PA, Poplack DG (eds) Principles and practice of pediatric oncology, 4th edn. Lippincott William and Wilkins, Philadelphia, pp 1–10Google Scholar
  25. 25.
    Margolin JF, Steuber CP, Poplack DG (2002) Acute lymphoblastic leukemia. In: Pizzo PA, Poplack DG (eds) Principles and practice of pediatric oncology. Lippincott, Williams & Wilkins, Philadelphia, pp 1605–1616Google Scholar
  26. 26.
    Robert J. Arceci, Ian M. Hann, Owen P. Smith, Pediatric hematology. 3 2006, Victoria: Blackwell Publishing. 826Google Scholar
  27. 27.
    Pui CH, Howard SC (2008) Current management and challenges of malignant disease in the CNS in paediatric leukaemia. Lancet Oncol 9(3):257–268CrossRefGoogle Scholar
  28. 28.
    Lipshultz SE et al (1991) Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 324(12):808–815CrossRefGoogle Scholar
  29. 29.
    Hughes RG, Kay HE (1982) Major bone lesions in acute lymphoblastic leukaemia. Med Pediatr Oncol 10(1):67–70CrossRefGoogle Scholar
  30. 30.
    Murphy RG, Greenberg ML (1990) Osteonecrosis in pediatric patients with acute lymphoblastic leukemia. Cancer 65(8):1717–1721CrossRefGoogle Scholar
  31. 31.
    Grundy RG et al (1997) Survival and endocrine outcome after testicular relapse in acute lymphoblastic leukaemia. Arch Dis Child 76(3):190–196CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Reddy KS, Perkins SL (2004) Advances in the diagnostic approach to childhood lymphoblastic malignant neoplasms. Am J Clin Pathol 122(Suppl):S3–S18PubMedGoogle Scholar
  33. 33.
    Head DR, Pui CH (1999) Diagnosis and classification. In: Pui CH (ed) Childhood leukemias. Cambridge University Press, Cambridge, pp 19–37Google Scholar
  34. 34.
    Vardiman JW et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114(5):937–951CrossRefGoogle Scholar
  35. 35.
    Carroll WL et al (2003) Pediatric acute lymphoblastic leukemia. Hematol Am Soc Hematol Educ Program 2003:102–131CrossRefGoogle Scholar
  36. 36.
    Hafiz MG, Mannan MA (2007) Serum lactate dehydrogenase level in childhood acute lymphoblastic leukemia. Bangladesh Med Res Counc Bull 33(3):88–91CrossRefGoogle Scholar
  37. 37.
    Hafiz MG, Rahman MM, Mannan MA (2008) Serum lactate dehydrogenase as a prognostic marker of childhood acute lymphoblastic leukemia. Mymensingh Med J 17(2):169–173PubMedGoogle Scholar
  38. 38.
    Lesnichenko IF et al (2008) Study of lactate dehydrogenase isoenzyme in the cerebrospinal fluid of patients with acute lymphoblastic leukemia. Vopr Onkol 54(1):59–61PubMedGoogle Scholar
  39. 39.
    Sung JJ et al (2011) Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding. Endoscopy 43(4):291–295CrossRefGoogle Scholar
  40. 40.
    Bain BJ et al (2002) Revised guideline on immunophenotyping in acute leukaemias and chronic lymphoproliferative disorders. Clin Lab Haematol 24(1):1–13CrossRefGoogle Scholar
  41. 41.
    Behm F, Campana D (1999) Immunophenotyping. In: Pui CH (ed) Acute leukemias. Cambridge University Press, Cambridge, pp 111–135Google Scholar
  42. 42.
    Van Dongen JJ (2003) Immunophenotyping of hematopoietic malignancies. Departement of Immunology, Erasmus University Medical Center, RotterdamGoogle Scholar
  43. 43.
    Campana D, Behm FG (2000) Immunophenotyping of leukemia. J Immunol Methods 243(1–2):59–75CrossRefGoogle Scholar
  44. 44.
    Bradstock KF (1993) The diagnostic and prognostic value of immunophenotyping in acute leukemia. Pathology 25(4):367–374CrossRefGoogle Scholar
  45. 45.
    Campana D, Coustan-Smith E, Janossy G (1990) Immunophenotyping in haematological diagnosis. Baillieres Clin Haematol 3(4):889–919CrossRefGoogle Scholar
  46. 46.
    Browman GP, Neame PB, Soamboonsrup P (1986) The contribution of cytochemistry and immunophenotyping to the reproducibility of the FAB classification in acute leukemia. Blood 68(4):900–905CrossRefGoogle Scholar
  47. 47.
    Coustan-Smith E et al (2000) Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood 96(8):2691–2696CrossRefGoogle Scholar
  48. 48.
    Howard SC et al (2005) Development of a regional flow cytometry center for diagnosis of childhood leukemia in Central America. Leukemia 19(3):323–325CrossRefGoogle Scholar
  49. 49.
    Orfao A et al (1999) Clinically useful information provided by the flow cytometric immunophenotyping of hematological malignancies: current status and future directions. Clin Chem 45(10):1708–1717PubMedGoogle Scholar
  50. 50.
    Cosset E et al (2011) Deregulation of TWIST-1 in the CD34+ compartment represents a novel prognostic factor in chronic myeloid leukemia. Blood 117(5):1673–1676CrossRefGoogle Scholar
  51. 51.
    Clinical study of 572 adult acute leukemia patients in Shanghai according to WHO classification (2007) Zhonghua Xue Ye Xue Za Zhi 28(7):444–448Google Scholar
  52. 52.
    Pui CH (1997) Acute lymphoblastic leukemia. Pediatr Clin N Am 44(4):831–846CrossRefGoogle Scholar
  53. 53.
    Pui CH (2009) Acute lymphoblastic leukemia: introduction. Semin Hematol 46(1):1–2CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Pui CH, Behm FG, Crist WM (1993) Clinical and biologic relevance of immunologic marker studies in childhood acute lymphoblastic leukemia. Blood 82(2):343–362CrossRefGoogle Scholar
  55. 55.
    Pui CH et al (1990) Heterogeneity of presenting features and their relation to treatment outcome in 120 children with T-cell acute lymphoblastic leukemia. Blood 75(1):174–179CrossRefGoogle Scholar
  56. 56.
    Campana D et al (1991) Stages of T-cell receptor protein expression in T-cell acute lymphoblastic leukemia. Blood 77(7):1546–1554CrossRefGoogle Scholar
  57. 57.
    Neame PB et al (1986) Classifying acute leukemia by immunophenotyping: a combined FAB-immunologic classification of AML. Blood 68(6):1355–1362CrossRefGoogle Scholar
  58. 58.
    Basso G et al (2001) New methodologic approaches for immunophenotyping acute leukemias. Haematologica 86(7):675–692PubMedGoogle Scholar
  59. 59.
    Williams SR et al (1997) Acute bilineage leukemia after chronic myelogenous leukemia. J Ky Med Assoc 95(9):393–396PubMedGoogle Scholar
  60. 60.
    Kobayashi N et al (2004) Bilineage acute leukemia of T-lymphoid and myeloid lineages. Haematologica 89(9):1139–1141PubMedGoogle Scholar
  61. 61.
    Pui CH et al (2002) Childhood acute lymphoblastic leukemia. Rev Clin Exp Hematol 6(2):161–180. discussion 200-2CrossRefGoogle Scholar
  62. 62.
    Matutes E et al (1997) Definition of acute biphenotypic leukemia. Haematologica 82(1):64–66PubMedGoogle Scholar
  63. 63.
    World Health Organization Classification of Tumours (2008) In: Jaffe ES et al (eds) Pathology and genetics tumours of haematopoietic and lymphoid tissues. IARC Press, LyonGoogle Scholar
  64. 64.
    Smith M et al (1996) Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol 14(1):18–24CrossRefGoogle Scholar
  65. 65.
    Bowman WP (1981) Childhood acute lymphocytic leukemia: progress and problems in treatment. Can Med Assoc J 124(2):129–142PubMedPubMedCentralGoogle Scholar
  66. 66.
    Hunger SP, Sung L, Howard SC (2009) Treatment strategies and regimens of graduated intensity for childhood acute lymphoblastic leukemia in low-income countries: a proposal. Pediatr Blood Cancer 52(5):559–565CrossRefGoogle Scholar
  67. 67.
    Sitaresmi MN et al (2008) Health-care providers’ compliance with childhood acute lymphoblastic leukemia protocol in Indonesia. Pediatr Blood Cancer 51(6):732–736CrossRefGoogle Scholar
  68. 68.
    Sitaresmi MN et al (2009) Chemotherapy-related side effects in childhood acute lymphoblastic leukemia in Indonesia: parental perceptions. J Pediatr Oncol Nurs 26(4):198–207CrossRefGoogle Scholar
  69. 69.
    Sitaresmi MN et al (2010) Treatment refusal and abandonment in childhood acute lymphoblastic leukemia in Indonesia: an analysis of causes and consequences. Psychooncology 19(4):361–367CrossRefGoogle Scholar
  70. 70.
    Davies HA, Lilleyman JS (1995) Compliance with oral chemotherapy in childhood lymphoblastic leukaemia. Cancer Treat Rev 21(2):93–103CrossRefGoogle Scholar
  71. 71.
    Pui CH, Evans WE (2006) Treatment of acute lymphoblastic leukemia. N Engl J Med 354(2):166–178CrossRefGoogle Scholar
  72. 72.
    Veerman AJ et al (2009) Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997–2004). Lancet Oncol 10(10):957–966CrossRefGoogle Scholar
  73. 73.
    Schrappe M et al (2000) Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group. Blood 95(11):3310–3322PubMedGoogle Scholar
  74. 74.
    Harms DO et al (2003) Thioguanine offers no advantage over mercaptopurine in maintenance treatment of childhood ALL: results of the randomized trial COALL-92. Blood 102(8):2736–2740CrossRefGoogle Scholar
  75. 75.
    Relling MV et al (1999) Prognostic importance of 6-mercaptopurine dose intensity in acute lymphoblastic leukemia. Blood 93(9):2817–2823CrossRefGoogle Scholar
  76. 76.
    Howard SC, Jones DP, Pui CH (2011) The tumor lysis syndrome. N Engl J Med 364(19):1844–1854CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Ozdemir MA et al (2009) Management of hyperleukocytosis and prevention of tumor lysis syndrome with low-dose prednisone continuous infusion in children with acute lymphoblastic leukemia. Acta Haematol 121(1):56–62CrossRefGoogle Scholar
  78. 78.
    Teuffel O et al (2008) Anemia and survival in childhood acute lymphoblastic leukemia. Haematologica 93(11):1652–1657CrossRefGoogle Scholar
  79. 79.
    Howard SC et al (2000) Safety of lumbar puncture for children with acute lymphoblastic leukemia and thrombocytopenia. JAMA 284(17):2222–2224CrossRefGoogle Scholar
  80. 80.
    Allen D et al (2007) Platelet transfusion in neonatal alloimmune thrombocytopenia. Blood 109(1):388–389CrossRefGoogle Scholar
  81. 81.
    Biswal S, Godnaik C (2013) Incidence and management of infections in patients with acute leukemia following chemotherapy in general wards. Ecancermedicalscience 7:310PubMedPubMedCentralGoogle Scholar
  82. 82.
    Boxer L, Dale DC (2002) Neutropenia: causes and consequences. Semin Hematol 39(2):75–81CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pediatric, Division of Hematology/Oncology, Dr Sardjito Hospital, Faculty of MedicineUniversitas Gadjah MadaYogyakartaIndonesia

Personalised recommendations