Çocukluk Çağı Akut Lenfoblastik Lösemisi

Year 2012, Volume: 12 Issue: 1, 6 - 15, 01.01.2012

Zeynep Karakaş Tuğçe Aksu Uzunhan

https://doi.org/10.5222/j.child.2012.006

Abstract

Birçok gelişmiş ülkede çocuklarda en yaygın ikinci ölüm nedeni olan kanser, ülkemizde ilk dört sıra içinde yer almaktadır. İmmatür lenfohematopoetik hücrelerin malign proliferasyonu ve birikimi olan lösemi, en sık görülen çocukluk çağı kanseridir. En sık görülen alt tipi olan akut lenfoblastik lösemi, vakaların % 75-80’ini oluşturur. Ülkemizde yıllık insidans hızı milyonda 34.4 olan akut len- foblastik lösemi remisyon indüksiyonu, intensifikasyon konsolidasyon ve idame fazlarından oluşan bir protokol ile tedavi edilir. Güçlendirilmiş tedaviler ile günümüzde beş yıllık olaysız sağ kalım % 80’in üzerinde bildirilmekte- dir. Akut lenfoblastik lösemi daha iyi anlaşıldıkça gelecekte sağ kalım oranları daha da artacaktır

Keywords

Akut lenfoblastik lösemi, çocuk, tedavi

Childhood Acute Lymphoblastic Leukemia

Abstract

While cancer is the second most common cause of death in children in many developed countries, it ranks among the first four in Turkey. Leukemia, which is the malign prolife- ration and accumulation of lymphopoetic cells, is the most common childhood cancer. The most common subtype, ie. acute lymphoblastic leukemia constitutes 75-80 % of all childhood leukemia cases. Acute lymphoblastic leukemia with a yearly incidence of 34.4 per million in Turkey is treated with a protocol that includes induction of remission, intensification consolidation and maintenance phases. Nowadays with reinforced treatment modalities, 5-year event-free survival is reported to be over 80 %. As the understanding of acute lymphoblastic leukemia improves in the future, then survival rates will increase further

Keywords

Acute lymphoblastic leukemia, childhood, treatment

References

• 1. Zuelzer WW, Inoue S, Thompson RI, et al. Long-term cytogenetic studies in acute leukemia of children: the nature of relapse. Am J Hematol 1976;1:143-90. http://dx.doi.org/10.1002/ajh.2830010202 PMid:1069473
• 2. Burchenal JH, Murphy ML. Long term survivors in acute leukemia. Cancer Res 1965;25:1491-4. PMid:5862991
• 3. Reiter A, Schrappe M, Ludwig W-D, et al. Chemotherapy in 998 unselected childhood ALL patients. Results and conclusions of the multicenter trial ALL-BFM ’86. Blood 1994;84: 3122-33. PMid:7949185
• 4. Gaynon PS, Steinherz PG, Bleyer WA, et al. Improved therapy for children with acute lymphoblastic leukemia and unfavorable presenting features: a follow-up report of the Children’s Cancer Group Study CCG-106. J Clin Oncol 1993;11:2234-42. PMid:8229139
• 5. Rivera GK, Raimondi SC, Williams DL, et al. Improved outcome in childhood acute lymphoblastic leukemia with reinforced early treatment and rotational combination chemotherapy. Lancet 1991;337:61-6. http://dx.doi.org/10.1016/0140-6736(91)90733-6
• 6. Buchanan GR, Rivera GK, Boyett JM, et al. Reinduction therapy in 297 children with acute lymphoblastic leukemia in first bone marrow relapse: A Pediatric Oncology Group study. Blood 1988;72:1286-92. PMid:3167209
• 7. Henze G, Fengler R, Hartmann R, et al. Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group. Blood 1991; 78: 1166-72. PMid:1878583
• 8. Pui CH. Acute lymphoblastic leukemia. In: Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT(eds). Williams Hematology, 7th edition. The McGraw-Hill Companies.2006:1321-42.
• 9. National Cancer Institute. SEER Cancer Statistics Review, 1975-2006. Erişim: http://seer.cancer.gov/csr/1975İ2006/.
• 10. Gurney JG, Severson RK, Davis S, et al. Incidence of cancer in children in the United States. Sex-, race-, and 1-year age-specific rates by histologic type. Cancer 1995;75(8):2186– 95. http://dx.doi.org/10.1002/1097-0142(19950415)75:83.0.CO;2-F
• 11. American Cancer Society. Cancer facts and figures 2008. Erişim: http://www.cancer.org.
• 12. Kutluk T. Çocukluk çağı kanserlerin epidemiolojisi. Klinik Gelişim 2007;20:5-12.
• 13. Shivakumar R, Tan W, Wilding GE, et al. Biologic features and treatment outcome of secondary acute lymphoblastic leukemia–a review of 101 cases. Ann Oncol 2008;19(9):1634-8. http://dx.doi.org/10.1093/annonc/mdn182 PMid:18467310 PMCid:2733065
• 14. Spector LG, Ross JA, Robison LL, et al. Epidemiology and etiology. In: Pui CH, editor. Childhood leukemias. New York: Cambridge University Press; 2006. p.48-66.
• 15. Wiemels JL, Cazzaniga G, Daniotti M, et al. Prenatal origin of acute lymphoblastic leukaemia in children. Lancet 1999; 354:1499-503. http://dx.doi.org/10.1016/S0140-6736(99)09403-9
• 16. Greaves M. Molecular genetics, natural history and demise of childhood leukaemia. Euro J Cancer 1999;35:1941-53. http://dx.doi.org/10.1016/S0959-8049(99)00296-8
• 17. Maia AT, Ford AM, Martineau M, et al. Molecular tracking of leukaemogenesis: insights from a triplet pregnancy. Blood 2000; 96(suppl 1):542a.
• 18. Eguchi-Ishimae M, Eguchi M, Ishii E, et al. Breakage and fusion of the TEL (ETV6) gene in immature B lymphocytes induced by apoptogenic signals. Blood 2001;97:737-43. http://dx.doi.org/10.1182/blood.V97.3.737 PMid:11157492
• 19. Nishimura R, Saikawa Y, Uehara T, et al. Detection of the TELAM1 fusion gene expression in febrile children with virus infections. Blood 2000;96 (suppl 1):542a.
• 20. Hjalgrim LL, Westergaard T, Rostgaard K, et al. Birth weight as a risk factor for childhood leukemia: a meta-analysis of 18 epidemiologic studies. Am J Epidemiol 2003;158:724- 35. http://dx.doi.org/10.1093/aje/kwg210 PMid:14561661
• 21. Ahlbom A, Day N, Feychting M, et al. A pooled analysis of magnetic fields and childhood leukaemia. Br J Cancer 2000; 83:692-8. http://dx.doi.org/10.1054/bjoc.2000.1376 PMid:10944614 PMCid:2363518
• 22. Buffler PA, Kwan ML, Reynolds P, Urayama KY. Environmental and genetic risk factors for childhood leukemia: appraising the evidence. Cancer Invest 2005;23:60-75. http://dx.doi.org/10.1081/CNV-46402 PMid:15779869
• 23. Kinlen L. Infections and immune factors in cancer: the role of epidemiology. Oncogene 2004;23:6341-8. http://dx.doi.org/10.1038/sj.onc.1207898 PMid:15322509
• 24. Greaves M. Infection, immune responses and the aetiology of childhood leukaemia. Nat Rev Cancer 2006;6:193-203. http://dx.doi.org/10.1038/nrc1816 PMid:16467884
• 25. Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med 2004;350:1535-48. http://dx.doi.org/10.1056/NEJMra023001 PMid:15071128
• 26. Armstrong SA, Look AT. Molecular genetics of acute lymphoblastic leukemia. J Clin Oncol 2005;23:6306-15. http://dx.doi.org/10.1200/JCO.2005.05.047 PMid:16155013
• 27. Yeoh EJ, Ross ME, Shurtleff SA, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 2002;1:133-43. http://dx.doi.org/10.1016/S1535-6108(02)00032-6
• 28. Lu J, Getz G, Miska EA, et al. MicroRNA expression profi- les classify human cancers. Nature 2005;435:834-8. http://dx.doi.org/10.1038/nature03702 PMid:15944708
• 29. Hong D, Gupta R, Ancliff O, et al. Initiating and cancerpropagating cells in TEL-AML1-associated childhood leukemia. Science 2008;319:336-9. http://dx.doi.org/10.1126/science.1150648 PMid:18202291
• 30. Smith OP, Hann IM. Clinical features and therapy of lymphoblastic leukemia. In: Arceci RJ, Hann IM, Smith OP(eds). Pediatric Hematology, Third Edition. Blackwell Publishing 2006:450-81. http://dx.doi.org/10.1002/9780470987001.ch20
• 31. Mainzer R, Taybi H. Thymic enlargement and pleural effusion: an unusual roentgenographic complex in childhood leukemia. Am J Roentgenol 1971;112:35-9.
• 32. Greydanus DE, Burgert O, Gilchrist GS, et al. Hypothalamic syndrome in children with acute lymphocytic leukemia. Mayo Clin Proc 1978;53:217-22. PMid:273134
• 33. Lauer SJ, Kirchner PAE. Identification of leukemic cells in the cerebrospinal fluid from children with acute lymphoblastic leukemia: advances and dilemmas. Am J Pediatr Hematol Oncol 1989;11:64-73.
• 34. Mastrangelo R, Poplack D, Bleyer A, et al. Report and recommendations of the Rome workshop concerning poor prognosis acute lymphoblastic leukemia in children: biologic bases for staging, stratification, and treatment. Med Pediatr Oncol 1986;14:191-4. http://dx.doi.org/10.1002/mpo.2950140317 PMid:3528788
• 35. Gilchrist GS, Tubergen DG, Sather HN et al. Low numbers of CSF blasts at diagnosis do not predict for the development of CNS leukemia in children with intermediate-risk acute lymphoblastic leukemia: a Children’s Cancer Group report. J Clin Oncol 1994;12:2594-600. PMid:7989934
• 36. Mahmoud HH, Rivera GK, Hancock ML, et al. Low leukocyte counts with blast cells in cerebrospinal fluid of children with newly diagnosed acute lymphoblastic leukemia. N Engl J Med 1993;329:314-9. http://dx.doi.org/10.1056/NEJM199307293290504 PMid:8321259
• 37. Kim TH, Hargreaves HK, Chan WC et al. Sequential testicular biopsies in childhood acute lymphocytic leukemia. Cancer 1986;57:1038-41. http://dx.doi.org/10.1002/1097-0142(19860301)57:53.0.CO;2-1
• 38. Nachman J, Palmer NF, Sather HN, et al. Open-wedge testicular biopsy in childhood acute lymphoblastic leukemia after two years of maintenance therapy: diagnostic accuracy and influence on outcome-a report from Children’s Cancer Study Group. Blood 1990;75:1051-5. PMid:2407298
• 39. Pui CH, Dahl GV, Bowman WP, et al. Elective testicular biopsy during chemotherapy for childhood leukaemia is of no clinical value. Lancet 1985;2:410-2. http://dx.doi.org/10.1016/S0140-6736(85)92735-7
• 40. Bowman W, Aur R, Hustu H, et al. Isolated testicular relapse in acute lymphocytic leukemia of childhood: categories and influence on survival. J Clin Oncol 1984;2:924. PMid:6589364
• 41. Leukemias In: Lanzkowsky P editor, Manual of Pediatric Hematology and Oncology: Elsevier Academic Press. San Diego, 2005;415-53. http://dx.doi.org/10.1016/B978-012088524-4/50018-2
• 42. Margolin JF, Steuber CP, Poplack DG. In: Acute lymphoblastic leukemia. Pizzo PA, Poplack DG(eds). Principles and Practice of Pediatric Oncology 4th edition. Lippincott Williams and Wilkins Publishers, 2001.
• 43. Pantazopoulos N, Sinks LF. Morphological criteria for prognostication of acute lymphoblastic leukaemia. Br J Haematol 1974;27:25-30. http://dx.doi.org/10.1111/j.1365-2141.1974.tb06770.x PMid:4527899
• 44. Lilleyman JS, Hann IM, Stevens RF, et al. Cytomorphology of childhood lymphoblastic leukaemia: A prospective study of 2000 patients. United Kingdom Medical Research Council’s Working Party on Childhood Leukaemia. Br J Haematol 1992;81:52-7. http://dx.doi.org/10.1111/j.1365-2141.1992.tb08170.x PMid:1520624
• 45. Shaw M, Humphrey G, Lawrence R, et al. Lack of prognostic value of the periodic-acid-Schiff reaction and blast cell size in childhood acute lymphocytic leukemia. Am J Hematol 1977;2:237. http://dx.doi.org/10.1002/ajh.2830020305 PMid:74208
• 46. Lee SL, Kopel S, Glidewell O. Cytomorphological determinants of prognosis in acute lymphoblastic leukemia of children. Semin Oncol 1976;3:209-17. PMid:1068527
• 47. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the acute leukaemias. French-AmericanBritish (FAB) co-operative group. Br J Haematol 1976;33:451- 8. http://dx.doi.org/10.1111/j.1365-2141.1976.tb03563.x PMid:188440
• 48. Bennett J, Catovsky D, Daniel MT. French-American British (FAB) Cooperative Group: the morphological classification of acute leukemias-concordance among observers and clinical correlation. Br J Hematol 1981;47:553. http://dx.doi.org/10.1111/j.1365-2141.1981.tb02684.x PMid:6938236
• 49. Foon KA, Todd RF III. Immunologic classification of leuke- mia and lymphoma. Blood 1986;68:1-31. PMid:2941082
• 50. Nadler LM, Korsmeyer SJ, Anderson KC, et al. B cell origin of non-T cell acute lymphoblastic leukemia. A model for discrete stages of neoplastic and normal pre-B cell diffe- rentiation. J Clin Invest 1984;74:332-40. http://dx.doi.org/10.1172/JCI111428 PMid:6378973 PMCid:370483
• 51. Pullen DJ, Falletta JM, Crist WM, et al. Southwest Oncology Group experience with immunological phenotyping in acute lymphocytic leukemia of childhood. Cancer Res 1981;41:4802-9. PMid:6975163
• 52. Miller DR, Leikin S, Albo V, et al. Prognostic importance of morphology (FAB classification) in childhood acute lymphob- lastic leukaemia (ALL). Br J Haematol 1981;48:199-206. PMid:6940623
• 53. Viana MB, Maurer HS, Ferenc C. Subclassification of acute lymphoblastic leukaemia in children: analysis of the reprodu- cibility of morphological criteria and prognostic implications. Br J Haematol 1980;44:383-8. http://dx.doi.org/10.1111/j.1365-2141.1980.tb05907.x PMid:6929702
• 54. Lilleyman JS, Hann IM, Stevens RF. The clinical significan- ce of blast cell morphology in childhood lymphoblastic leuka- emia. Med Pediatr Oncol 1986;14:144-7. http://dx.doi.org/10.1002/mpo.2950140308 PMid:3462461
• 55. Pui CH, Evans WE. Acute lymphoblastic leukemia. N Engl J Med 1998;339(9):605-15. http://dx.doi.org/10.1056/NEJM199808273390907 PMid:9718381
• 56. Béné MC, Bernier M, Castoldi G, et al. Impact of immunop- henotyping on management of acute leukemias. Haematologica 1999;84(11):1024-34. PMid:10553164
• 57. Ludwig WD, Reiter A, Löffler H, et al. Immunophenotypic features of childhood and adult acute lymphoblastic leukemia (ALL): experience of the German Multicentre Trials ALLBFM and GMALL. Leuk Lymphoma 1994;13 Suppl 1:71-6. http://dx.doi.org/10.3109/10428199409052679 PMid:8075585
• 58. Patte C, Auperin A, Michon J, Behrendt H. The Société Française d’Oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor bur- den and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 2001;97:3370-9. http://dx.doi.org/10.1182/blood.V97.11.3370 PMid:11369626
• 59. Woessmann W, Seidemann K, Mann G, et al. The impact of the methotrexate administration schedule and dose in the tre- atment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95. Blood 2005; 105:948-58. http://dx.doi.org/10.1182/blood-2004-03-0973 PMid:15486066
• 60. Lee EJ, Petroni GR, Schiffer CA, et al. Brief-duration highintensity chemotherapy for patients with small noncleavedcell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol 2001;19:4014-22. PMid:11600602
• 61. Pui CH, Evans WE. Treatment of acute lymphoblastic leuke- mia. N Engl J Med 2006;354:166-78. http://dx.doi.org/10.1056/NEJMra052603 PMid:16407512
• 62. Pui CH, Sandlund JT, Pei D, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children’s Research Hospital. Blood 2004;104:2690-6. http://dx.doi.org/10.1182/blood-2004-04-1616 PMid:15251979
• 63. Loh ML, Goldwasser MA, Silverman LB, et al. Prospective analysis of TEL/AML1-positive patients treated on DanaFarber Cancer Institute Consortium Protocol 95-01. Blood 2006;107:4508-13. http://dx.doi.org/10.1182/blood-2005-08-3451 PMid:16493009 PMCid:1895800
• 64. Bürger B, Zimmermann M, Mann G, et al. Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture. J Clin Oncol 2003;21:179-81. PMid:12525506
• 65. Nachman JB, Sather HN, Sensel MG, et al. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med 1998;338:1663-71. http://dx.doi.org/10.1056/NEJM199806043382304 PMid:9614257
• 66. Schrappe M, Reiter A, Ludwig WD, et al. Improved outco- me in childhood acute lymphoblastic leukemia despite redu- ced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. Blood 2000;95:3310-22. PMid:10828010
• 67. Pui CH, Relling MV, Evans WE. Is mega dose of methotre- xate beneficial to patients with acute lymphoblastic leukemia? Leuk Lymphoma 2006;47:2431-2. http://dx.doi.org/10.1080/10428190600955837
• 68. Kager L, Cheok M, Yang W, et al. Folate pathway gene expression differs in subtypes of acute lymphoblastic leuke- mia and influences methotrexate pharmacodynamics. J Clin Invest 2005;115:110-17. PMid:15630450 PMCid:539195
• 69. Nathan PC, Whitcomb T, Wolters PL, et al. Very high-dose methotrexate (33·6 g/m2 ) as central nervous system preventive therapy for childhood acute lymphoblastic leukemia: results of National Cancer Institute/Children’s Cancer Group trials CCG-191P, CCG-134P, and CCG-144P. Leuk Lymphoma 2006;47:2488-504. http://dx.doi.org/10.1080/10428190600942769
• 70. Skärby TV, Anderson H, Heldrup J, et al. High leucovorin doses during high-dose methotrexate treatment may reduce the cure rate in childhood acute lymphoblastic leukemia. Leukemia 2006;20:1955-62. http://dx.doi.org/10.1038/sj.leu.2404404 PMid:16990760
• 71. Toyoda Y, Manabe A, Tsuchida M, et al. Six months of maintenance chemotherapy after intensified treatment for acute lymphoblastic leukemia of childhood. J Clin Oncol 2000;18:1508-16. PMid:10735899
• 72. Jacobs SS, Stork LC, Bostrom BC, et al. Substitution of oral and intravenous thioguanine for mercaptopurine in a treatment regimen for children with standard risk acute lymphoblastic leukemia: a collaborative Children’s Oncology Group/ National Cancer Institute pilot trial (CCG-1942). Pediatr Blood Cancer 2007;49:250-5. http://dx.doi.org/10.1002/pbc.20964
• 73. Harms DO, Gobel U, Spaar HJ, et al. Thioguanine offers no advantage over mercaptopurine in maintenance treatment of childhood ALL: results of the randomized trial COALL-92. Blood 2003;102:2736-40. http://dx.doi.org/10.1182/blood-2002-08-2372 PMid:12843002
• 74. Stork LC, Sather H, Hutchinson RJ, et al. Comparison of mercaptopurine (MP) with thioguanine (TG) and IT methotre- xate (ITM) with IT “triples” (ITT) in children with SR-ALL: results of CCG-1952. Blood 2002;100:156a.
• 75. Vora A, Mitchell CD, Lennard L, et al. Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial. Lancet 2006;368:1339-48. http://dx.doi.org/10.1016/S0140-6736(06)69558-5
• 76. Lennard L, Richards S, Cartwright CS, et al. The thiopuri- ne methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clin Pharmacol Ther 2006;80:375-83. http://dx.doi.org/10.1016/j.clpt.2006.07.002
• 77. Conter V, Valsecchi MG, Silvestri D, et al. Pulses of vincris- tine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leuka- emia: a multicentre randomised trial. Lancet 2007;369:123- 31. http://dx.doi.org/10.1016/S0140-6736(07)60073-7