Childhood Leukemias Review

Öz

Leukemia is a curable disease with unknown etiologyin the pediatric age group Cure rates approaching 75 can be achieved with combination chemotherapy but this percentage disguises success rates that vary from 10 to 90 with the different biological and clinical subtypes of the disease Studies pointing to environmental factors such as infections and chemical exposures indicate possible risk factors in childhood leukemia Primary prevention should remain an ultimate goal along with further advancements in therapeutic and control of infection In this review current data for the etiology diagnostic and therapy modialities are discussed Keywords: child chemical agents infection leukemia

Anahtar Kelimeler

• -

Çocukluk çağı lösemileri Derleme

Öz

Çocukluk çağında lösemi sebebi bilinmeyen tedavi edilebilen bir hastalıktır Çoklu tedavi yöntemleri ile iyileşme oranı 75 civarına ulaşsa da bu rakam değişik biyolojik alt sınıflar nedeniyle 10 ile 90 arasında çok büyük fark gösteren sonuçları maskelemektedir Enfeksiyon ve kimyasal maddelere dikkat çeken çalışmalar çocukluk çağı lösemisi için olası etmenleri işaret etmektedirler Hastalığın önlenmesi hedefimiz olmalı bu sırada enfeksiyon kontrolü ve tedavisi de göz önüne alınmalıdır Bu derlemede etioloji tanı ve tedavi hakkındaki son bilgiler ele alınmıştır Anahtar kelimeler: çocuk enfeksiyon kimyasal madde lösemi

Anahtar Kelimeler

• çocuk, enfeksiyon, kimyasal madde, lösemi

Kaynakça

1. Chen AY, Liu LF. DNA topoisomerases: essential enzymes and lethal targets. Annu Rev Pharmacol Toxicol 1994: 34: 191-218. 8. Greaves M. A natural history for pediatric acute leukemia. Blood 1993: 82: 1043- 51. 9. Martyn TS. The mechanism of benzene-induced leukemia: A hypothesis and speculations on the causes of leukemia. Environ Health Perspect 1996: 104: 1219- 25.
2. Harrison RM, Leung PL, Sommervaille L, Smith R, Gilman E. Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations. Occup Environ Med, 1999: 56: 774- 80.
3. Kohli S, Brage HN, Löfman O. Childhood leukaemia in areas with different radon levels: a spatial and temporal analysis using GIS. J Epidemiol Community Health 2000: 54: 822- 6.
4. Menegaux F, Baruchel A, Bertrand Y, et al. Household exposure to pesticides and risk of childhood acute leukaemia. Occup Environ Med 2006; 63: 131-4.
5. Kwa SL, Fine LJ. The association between parental occupation and childhood malignancy. J Occup Med 1980: 22: 792- 4.
6. McKinney PA, Fear NT, Stockton D. Parental occupation at periconception: findings from the United Kingdom Childhood Cancer Study. Occup Environ Med 2003; 60: 901- 9.
7. Julie AR, Cindy KB, Andrew FO, et al. Periconceptional vitamin use and leukemia risk in children with Down syndrome. Cancer 2005: 104: 405- 10.
8. Wanqing W, Xiao OS, John DP, et al. Parental medication use and risk of childhood acute lymphoblastic leukemia Cancer 2002; 95: 1786- 94.

9. Lehtinen M, Koskela P, Ögmundsdottir MH, et al. Maternal herpesvirus infections and risk of acute lymphoplastic leukemia in the offspring. Am J Epidemiol 2003; 158: 207- 13.
10. Lehtinen M, Koskela P, Ögmundsdottir MH, et al. Antenatal herpesvirus infection: leukemia risk in the infant? Am J Epidemiol 2005; 162: 662 - 7.
11. Lehtinen M, Ögmundsdottir HM, Bloigu A, et al. Associations between three types of maternal bacterial infection and risk of leukemia in the offspring. Am J Epidemiol 2005 162: 662- 7.
12. Altieri A, Castro F, Bermejo JL, Hemminki K. Number of siblings and the risk of lymphoma, leukemia, and myeloma by histopathology. Cancer Epidemiol Prev 2006; 15: 1281- 6.
13. Groves F, Sinha D, Auvinen A. Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia. Br J Cancer 2002; 511- 2.
14. MacKenzie J, Greaves MF, Eden TOB, et al. The putative role of transforming viruses in childhood acute lymphoblastic leukemia. Hematologica 2006; 91: 240- 3.
15. Greaves MF. Aetiology of acute leukemia. Lancet 1997; 3489: 344- 9.
16. Ford AM, Ridge SA, Cabrera ME, et al. In utero rearrangements in the trithorax-related oncogene in infant leukaemias. Nature 1993; 363, 358 - 60.
17. Wiemels JL, Ford AM, Van Wering ER, Postma A, Greaves M. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero. Blood 1999; 94: 1057- 62.
18. Gale KB, Ford AM, Repp R, et al. Backtracking leukemia to birth: Identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA 1997; 94: 13950-4.
19. Wiemels JL, Cazzaniga G, Daniotti M, et al. Prenatal origin of acute lymphoblastic leukemia in c hildren. Th e Lan cet 1999; 354: 1499- 1503.
20. McHale CM, Wiemels JL, Zhang L, et al. Prenatal origin of TEL-AML1-positive acute lymphoblastic leukemia in children born in California. Genes Chromosomes Cancer 2003; 37: 36- 43.
21. Wiemels JL, Xiao Z, Buffler PA, et al. In utero origin of t (8;21) AML1-ETO translocations in childhood acute myeloid leukemia. Blood 2002; 99: 3801- 5.
22. McHale CM, Wiemels JL, Zhang L, et al . Prenatal origin of childhood acute myeloid leukemias harboring chromosomal rearrangements t(15;17) and inv(16). Blood 2003; 101: 4640- 1.
23. Greaves M. Molecular genetics, natural history and the demise of childhood leukaemia. Eur J Cancer. 1999; 35: 1941- 53.
24. Wiemels JL, Pagnamenta A, Taylor GM, Eden OB, Alexander FE, Greaves MF. A lack of a functional NAD(P)H: Quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions. Cancer Res 1999; 59: 4095- 9.
25. Wiemels JL, Smith RN, Taylor GM, et al. Methylenetetrah- ydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA 2001; 98: 4004- 9.
26. Thompson JR, FitzGerald P, Willoughby MLN, Armstrong BK. Maternal folate supplementation in pregnancy and protection against common acute lymphoblastic leukaemia in childhood: a case-control study. Lancet 2001; 358: 1935- 40.
27. Fenaux P , Chommi ene C, Degos L. Treat ment of acute promyelocytic leukemia. Best Pract Res Clin Haematol 2001; 14: 153- 74.
28. Pui C-H, Crist WM. Biology and treatment of acute lymphoblastic leukemia. J Pediatr 1994; 124: 491- 503.
29. Sağlamer L, Ulu kutlu L, Yıldız İ. Im proved prognosis in ALL with modified BFM protocols-Preliminary results from Turkey. Haematol Blood Transfus 1994; 36: 347- 51.
30. Ercan TE, Soycan LY, Apak H, et al. Antibody titers and immune response to diphteria-tetanus-pertussis and measles-mumps- rubella vaccination in children treated for acute lymphoblastic leukemia. J Ped Hem/Oncol 2005; 27: 273- 7.
31. İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Çocuk Hematoloji-Onkoloji Bilim Dalı 1.
32. Miller DR. Hematologic malignancies: leukemia and lymphoma.
33. In: Miller RM, Baehner RL, Miller LP (eds). Blood Diseases
34. of Infancy and Childhood Xth. ed. Mosby, 2005: 660- 768. 2.
35. Fırat D, Çelik İ. Cancer statistics in Turkey and in the world
36. 1995. Turkish Association For the Cancer Research and
37. Control. Ankara, 1998. 3.
38. Http://seer.cancer.gov/csr/1975_2003/ results_ merged/ sect_ 13_leukemia.pdf 4.
39. McDonald TA, Yeowell OCK, Rappaport SM. Comparison
40. of protein adducts of benzene oxide and benzoquinone in the
41. blood and bone marrow of rats and mice exposed to [14C/
42. C6]benzene. Cancer Res 1994: 54: 4907-14. 5. Smith MT. Quinones as mutagens, carcinogens, and anticancer agents: introduction and overview. J Toxicol Environ Health 1985: 16: 665- 72. 6. Anderson RD, Berger NA. International commission for protection against environmental mutagens and carcinogens. Mutagenicity and carcinogenicity of topoisomerase-interactive agents. Mutat Res 1994: 309: 109- 42.
43. Chen AY, Liu LF. DNA topoisomerases: essential enzymes and lethal targets. Annu Rev Pharmacol Toxicol 1994: 34: 191-218. 8. Greaves M. A natural history for pediatric acute leukemia. Blood 1993: 82: 1043- 51. 9. Martyn TS. The mechanism of benzene-induced leukemia: A hypothesis and speculations on the causes of leukemia. Environ Health Perspect 1996: 104: 1219- 25.
44. Harrison RM, Leung PL, Sommervaille L, Smith R, Gilman E. Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations. Occup Environ Med, 1999: 56: 774- 80.
45. Kohli S, Brage HN, Löfman O. Childhood leukaemia in areas with different radon levels: a spatial and temporal analysis using GIS. J Epidemiol Community Health 2000: 54: 822- 6.
46. Menegaux F, Baruchel A, Bertrand Y, et al. Household exposure to pesticides and risk of childhood acute leukaemia. Occup Environ Med 2006; 63: 131-4.
47. Kwa SL, Fine LJ. The association between parental occupation and childhood malignancy. J Occup Med 1980: 22: 792- 4.
48. McKinney PA, Fear NT, Stockton D. Parental occupation at periconception: findings from the United Kingdom Childhood Cancer Study. Occup Environ Med 2003; 60: 901- 9.
49. Julie AR, Cindy KB, Andrew FO, et al. Periconceptional vitamin use and leukemia risk in children with Down syndrome. Cancer 2005: 104: 405- 10.
50. Wanqing W, Xiao OS, John DP, et al. Parental medication use and risk of childhood acute lymphoblastic leukemia Cancer 2002; 95: 1786- 94.
51. Lehtinen M, Koskela P, Ögmundsdottir MH, et al. Maternal herpesvirus infections and risk of acute lymphoplastic leukemia in the offspring. Am J Epidemiol 2003; 158: 207- 13.
52. Lehtinen M, Koskela P, Ögmundsdottir MH, et al. Antenatal herpesvirus infection: leukemia risk in the infant? Am J Epidemiol 2005; 162: 662 - 7.
53. Lehtinen M, Ögmundsdottir HM, Bloigu A, et al. Associations between three types of maternal bacterial infection and risk of leukemia in the offspring. Am J Epidemiol 2005 162: 662- 7.
54. Altieri A, Castro F, Bermejo JL, Hemminki K. Number of siblings and the risk of lymphoma, leukemia, and myeloma by histopathology. Cancer Epidemiol Prev 2006; 15: 1281- 6.
55. Groves F, Sinha D, Auvinen A. Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia. Br J Cancer 2002; 511- 2.
56. MacKenzie J, Greaves MF, Eden TOB, et al. The putative role of transforming viruses in childhood acute lymphoblastic leukemia. Hematologica 2006; 91: 240- 3.
57. Greaves MF. Aetiology of acute leukemia. Lancet 1997; 3489: 344- 9.
58. Ford AM, Ridge SA, Cabrera ME, et al. In utero rearrangements in the trithorax-related oncogene in infant leukaemias. Nature 1993; 363, 358 - 60.
59. Wiemels JL, Ford AM, Van Wering ER, Postma A, Greaves M. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero. Blood 1999; 94: 1057- 62.
60. Gale KB, Ford AM, Repp R, et al. Backtracking leukemia to birth: Identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA 1997; 94: 13950-4.
61. Wiemels JL, Cazzaniga G, Daniotti M, et al. Prenatal origin of acute lymphoblastic leukemia in children. The Lancet 1999; 354: 1499- 1503.
62. McHale CM, Wiemels JL, Zhang L, et al. Prenatal origin of TEL-AML1-positive acute lymphoblastic leukemia in children born in California. Genes Chromosomes Cancer 2003; 37: 36- 43.
63. Wiemels JL, Xiao Z, Buffler PA, et al. In utero origin of t (8;21) AML1-ETO translocations in childhood acute myeloid leukemia. Blood 2002; 99: 3801- 5.
64. McHale CM, Wiemels JL, Zhang L, et al . Prenatal origin of childhood acute myeloid leukemias harboring chromosomal rearrangements t(15;17) and inv(16). Blood 2003; 101: 4640- 1.
65. Greaves M. Molecular genetics, natural history and the demise of childhood leukaemia. Eur J Cancer. 1999; 35: 1941- 53.
66. Wiemels JL, Pagnamenta A, Taylor GM, Eden OB, Alexander FE, Greaves MF. A lack of a functional NAD(P)H: Quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions. Cancer Res 1999; 59: 4095- 9.
67. Wiemels JL, Smith RN, Taylor GM, et al. Methylenetetrah- ydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA 2001; 98: 4004- 9.
68. Thompson JR, FitzGerald P, Willoughby MLN, Armstrong BK. Maternal folate supplementation in pregnancy and protection against common acute lymphoblastic leukaemia in childhood: a case-control study. Lancet 2001; 358: 1935- 40.
69. Fenaux P, Chommiene C, Degos L. Treatment of acute promyelocytic leukemia. Best Pract Res Clin Haematol 2001; 14: 153- 74.
70. Pui C-H, Crist WM. Biology and treatment of acute lymphoblastic leukemia. J Pediatr 1994; 124: 491- 503.
71. Sağlamer L, Ulukutlu L, Yıldız İ. Improved prognosis in ALL with modified BFM protocols-Preliminary results from Turkey. Haematol Blood Transfus 1994; 36: 347- 51.
72. Ercan TE, Soycan LY, Apak H, et al. Antibody titers and immune response to diphteria-tetanus-pertussis and measles-mumps- rubella vaccination in children treated for acute lymphoblastic leukemia. J Ped Hem/Oncol 2005; 27: 273- 7.
73. Türk Pediatri Arşivi 2006; 41: 189- 96
74. Hilmi Apak. Çocukluk çağı lösemileri 1.
75. Miller DR. Hematologic malignancies: leukemia and lymphoma.
76. In: Miller RM, Baehner RL, Miller LP (eds). Blood Diseases
77. of Infancy and Childhood Xth. ed. Mosby, 2005: 660- 768. 2.
78. Fırat D, Çelik İ. Cancer statistics in Turkey and in the world
79. 1995. Turkish Association For the Cancer Research and
80. Control. Ankara, 1998. 3.
81. Http://seer.cancer.gov/csr/1975_2003/ results_ merged/ sect_ 13_leukemia.pdf 4.
82. McDonald TA, Yeowell OCK, Rappaport SM. Comparison
83. of protein adducts of benzene oxide and benzoquinone in the
84. blood and bone marrow of rats and mice exposed to [14C/
85. C6]benzene. Cancer Res 1994: 54: 4907-14. 5. Smith MT. Quinones as mutagens, carcinogens, and anticancer agents: introduction and overview. J Toxicol Environ Health 1985: 16: 665- 72. 6. Anderson RD, Berger NA. International commission for protection against environmental mutagens and carcinogens. Mutagenicity and carcinogenicity of topoisomerase-interactive agents. Mutat Res 1994: 309: 109- 42.
86. Chen AY, Liu LF. DNA topoisomerases: essential enzymes and lethal targets. Annu Rev Pharmacol Toxicol 1994: 34: 191-218. 8. Greaves M. A natural history for pediatric acute leukemia. Blood 1993: 82: 1043- 51. 9. Martyn TS. The mechanism of benzene-induced leukemia: A hypothesis and speculations on the causes of leukemia. Environ Health Perspect 1996: 104: 1219- 25.
87. Harrison RM, Leung PL, Sommervaille L, Smith R, Gilman E. Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations. Occup Environ Med, 1999: 56: 774- 80.
88. Kohli S, Brage HN, Löfman O. Childhood leukaemia in areas with different radon levels: a spatial and temporal analysis using GIS. J Epidemiol Community Health 2000: 54: 822- 6.
89. Menegaux F, Baruchel A, Bertrand Y, et al. Household exposure to pesticides and risk of childhood acute leukaemia. Occup Environ Med 2006; 63: 131-4.
90. Kwa SL, Fine LJ. The association between parental occupation and childhood malignancy. J Occup Med 1980: 22: 792- 4.
91. McKinney PA, Fear NT, Stockton D. Parental occupation at periconception: findings from the United Kingdom Childhood Cancer Study. Occup Environ Med 2003; 60: 901- 9.
92. Julie AR, Cindy KB, Andrew FO, et al. Periconceptional vitamin use and leukemia risk in children with Down syndrome. Cancer 2005: 104: 405- 10.
93. Wanqing W, Xiao OS, John DP, et al. Parental medication use and risk of childhood acute lymphoblastic leukemia Cancer 2002; 95: 1786- 94.
94. Lehtinen M, Koskela P, Ögmundsdottir MH, et al. Maternal herpesvirus infections and risk of acute lymphoplastic leukemia in the offspring. Am J Epidemiol 2003; 158: 207- 13.
95. Lehtinen M, Koskela P, Ögmundsdottir MH, et al. Antenatal herpesvirus infection: leukemia risk in the infant? Am J Epidemiol 2005; 162: 662 - 7.
96. Lehtinen M, Ögmundsdottir HM, Bloigu A, et al. Associations between three types of maternal bacterial infection and risk of leukemia in the offspring. Am J Epidemiol 2005 162: 662- 7.
97. Altieri A, Castro F, Bermejo JL, Hemminki K. Number of siblings and the risk of lymphoma, leukemia, and myeloma by histopathology. Cancer Epidemiol Prev 2006; 15: 1281- 6.
98. Groves F, Sinha D, Auvinen A. Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia. Br J Cancer 2002; 511- 2.
99. MacKenzie J, Greaves MF, Eden TOB, et al. The putative role of transforming viruses in childhood acute lymphoblastic leukemia. Hematologica 2006; 91: 240- 3.
100. Greaves MF. Aetiology of acute leukemia. Lancet 1997; 3489: 344- 9.
101. Ford AM, Ridge SA, Cabrera ME, et al. In utero rearrangements in the trithorax-related oncogene in infant leukaemias. Nature 1993; 363, 358 - 60.
102. Wiemels JL, Ford AM, Van Wering ER, Postma A, Greaves M. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero. Blood 1999; 94: 1057- 62.
103. Gale KB, Ford AM, Repp R, et al. Backtracking leukemia to birth: Identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA 1997; 94: 13950-4.
104. Wiemels JL, Cazzaniga G, Daniotti M, et al. Prenatal origin of acute lymphoblastic leukemia in children. The Lancet 1999; 354: 1499- 1503.
105. McHale CM, Wiemels JL, Zhang L, et al. Prenatal origin of TEL-AML1-positive acute lymphoblastic leukemia in children born in California. Genes Chromosomes Cancer 2003; 37: 36- 43.
106. Wiemels JL, Xiao Z, Buffler PA, et al. In utero origin of t (8;21) AML1-ETO translocations in childhood acute myeloid leukemia. Blood 2002; 99: 3801- 5.
107. McHale CM, Wiemels JL, Zhang L, et al . Prenatal origin of childhood acute myeloid leukemias harboring chromosomal rearrangements t(15;17) and inv(16). Blood 2003; 101: 4640- 1.
108. Greaves M. Molecular genetics, natural history and the demise of childhood leukaemia. Eur J Cancer. 1999; 35: 1941- 53.
109. Wiemels JL, Pagnamenta A, Taylor GM, Eden OB, Alexander FE, Greaves MF. A lack of a functional NAD(P)H: Quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions. Cancer Res 1999; 59: 4095- 9.
110. Wiemels JL, Smith RN, Taylor GM, et al. Methylenetetrah- ydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA 2001; 98: 4004- 9.
111. Thompson JR, FitzGerald P, Willoughby MLN, Armstrong BK. Maternal folate supplementation in pregnancy and protection against common acute lymphoblastic leukaemia in childhood: a case-control study. Lancet 2001; 358: 1935- 40.
112. Fenaux P, Chommiene C, Degos L. Treatment of acute promyelocytic leukemia. Best Pract Res Clin Haematol 2001; 14: 153- 74.
113. Pui C-H, Crist WM. Biology and treatment of acute lymphoblastic leukemia. J Pediatr 1994; 124: 491- 503.
114. Sağlamer L, Ulukutlu L, Yıldız İ. Improved prognosis in ALL with modified BFM protocols-Preliminary results from Turkey. Haematol Blood Transfus 1994; 36: 347- 51.
115. Ercan TE, Soycan LY, Apak H, et al. Antibody titers and immune response to diphteria-tetanus-pertussis and measles-mumps- rubella vaccination in children treated for acute lymphoblastic leukemia. J Ped Hem/Oncol 2005; 27: 273- 7.
116. Türk Pediatri Arşivi 2006; 41: 189- 96
117. Hilmi Apak. Çocukluk çağı lösemileri
118. Hilmi Apak. Çocukluk çağı lösemileri 1.
119. Miller DR. Hematologic malignancies: leukemia and lymphoma.
120. In: Miller RM, Baehner RL, Miller LP (eds). Blood Diseases
121. of Infancy and Childhood Xth. ed. Mosby, 2005: 660- 768. 2.
122. Fırat D, Çelik İ. Cancer statistics in Turkey and in the world
123. 1995. Turkish Association For the Cancer Research and
124. Control. Ankara, 1998. 3.
125. Http://seer.cancer.gov/csr/1975_2003/ results_ merged/ sect_ 13_leukemia.pdf 4.
126. McDonald TA, Yeowell OCK, Rappaport SM. Comparison
127. of protein adducts of benzene oxide and benzoquinone in the
128. blood and bone marrow of rats and mice exposed to [14C/
129. C6]benzene. Cancer Res 1994: 54: 4907-14. 5. Smith MT. Quinones as mutagens, carcinogens, and anticancer agents: introduction and overview. J Toxicol Environ Health 1985: 16: 665- 72. 6. Anderson RD, Berger NA. International commission for protection against environmental mutagens and carcinogens. Mutagenicity and carcinogenicity of topoisomerase-interactive agents. Mutat Res 1994: 309: 109- 42.
130. Chen AY, Liu LF. DNA topoisomerases: essential enzymes and lethal targets. Annu Rev Pharmacol Toxicol 1994: 34: 191-218. 8. Greaves M. A natural history for pediatric acute leukemia. Blood 1993: 82: 1043- 51. 9. Martyn TS. The mechanism of benzene-induced leukemia: A hypothesis and speculations on the causes of leukemia. Environ Health Perspect 1996: 104: 1219- 25.
131. Harrison RM, Leung PL, Sommervaille L, Smith R, Gilman E. Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations. Occup Environ Med, 1999: 56: 774- 80.
132. Kohli S, Brage HN, Löfman O. Childhood leukaemia in areas with different radon levels: a spatial and temporal analysis using GIS. J Epidemiol Community Health 2000: 54: 822- 6.
133. Menegaux F, Baruchel A, Bertrand Y, et al. Household exposure to pesticides and risk of childhood acute leukaemia. Occup Environ Med 2006; 63: 131-4.
134. Kwa SL, Fine LJ. The association between parental occupation and childhood malignancy. J Occup Med 1980: 22: 792- 4.
135. McKinney PA, Fear NT, Stockton D. Parental occupation at periconception: findings from the United Kingdom Childhood Cancer Study. Occup Environ Med 2003; 60: 901- 9.
136. Julie AR, Cindy KB, Andrew FO, et al. Periconceptional vitamin use and leukemia risk in children with Down syndrome. Cancer 2005: 104: 405- 10.
137. Wanqing W, Xiao OS, John DP, et al. Parental medication use and risk of childhood acute lymphoblastic leukemia Cancer 2002; 95: 1786- 94.
138. Lehtinen M, Koskela P, Ögmundsdottir MH, et al. Maternal herpesvirus infections and risk of acute lymphoplastic leukemia in the offspring. Am J Epidemiol 2003; 158: 207- 13.
139. Lehtinen M, Koskela P, Ögmundsdottir MH, et al. Antenatal herpesvirus infection: leukemia risk in the infant? Am J Epidemiol 2005; 162: 662 - 7.
140. Lehtinen M, Ögmundsdottir HM, Bloigu A, et al. Associations between three types of maternal bacterial infection and risk of leukemia in the offspring. Am J Epidemiol 2005 162: 662- 7.
141. Altieri A, Castro F, Bermejo JL, Hemminki K. Number of siblings and the risk of lymphoma, leukemia, and myeloma by histopathology. Cancer Epidemiol Prev 2006; 15: 1281- 6.
142. Groves F, Sinha D, Auvinen A. Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia. Br J Cancer 2002; 511- 2.
143. MacKenzie J, Greaves MF, Eden TOB, et al. The putative role of transforming viruses in childhood acute lymphoblastic leukemia. Hematologica 2006; 91: 240- 3.
144. Greaves MF. Aetiology of acute leukemia. Lancet 1997; 3489: 344- 9.
145. Ford AM, Ridge SA, Cabrera ME, et al. In utero rearrangements in the trithorax-related oncogene in infant leukaemias. Nature 1993; 363, 358 - 60.
146. Wiemels JL, Ford AM, Van Wering ER, Postma A, Greaves M. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero. Blood 1999; 94: 1057- 62.
147. Gale KB, Ford AM, Repp R, et al. Backtracking leukemia to birth: Identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA 1997; 94: 13950-4.
148. Wiemels JL, Cazzaniga G, Daniotti M, et al. Prenatal origin of acute lymphoblastic leukemia in children. The Lancet 1999; 354: 1499- 1503.
149. McHale CM, Wiemels JL, Zhang L, et al. Prenatal origin of TEL-AML1-positive acute lymphoblastic leukemia in children born in California. Genes Chromosomes Cancer 2003; 37: 36- 43.
150. Wiemels JL, Xiao Z, Buffler PA, et al. In utero origin of t (8;21) AML1-ETO translocations in childhood acute myeloid leukemia. Blood 2002; 99: 3801- 5.
151. McHale CM, Wiemels JL, Zhang L, et al . Prenatal origin of childhood acute myeloid leukemias harboring chromosomal rearrangements t(15;17) and inv(16). Blood 2003; 101: 4640- 1.
152. Greaves M. Molecular genetics, natural history and the demise of childhood leukaemia. Eur J Cancer. 1999; 35: 1941- 53.
153. Wiemels JL, Pagnamenta A, Taylor GM, Eden OB, Alexander FE, Greaves MF. A lack of a functional NAD(P)H: Quinone oxidoreductase allele is selectively associated with pediatric leukemias that have MLL fusions. Cancer Res 1999; 59: 4095- 9.
154. Wiemels JL, Smith RN, Taylor GM, et al. Methylenetetrah- ydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci USA 2001; 98: 4004- 9.
155. Thompson JR, FitzGerald P, Willoughby MLN, Armstrong BK. Maternal folate supplementation in pregnancy and protection against common acute lymphoblastic leukaemia in childhood: a case-control study. Lancet 2001; 358: 1935- 40.
156. Fenaux P, Chommiene C, Degos L. Treatment of acute promyelocytic leukemia. Best Pract Res Clin Haematol 2001; 14: 153- 74.
157. Pui C-H, Crist WM. Biology and treatment of acute lymphoblastic leukemia. J Pediatr 1994; 124: 491- 503.
158. Sağlamer L, Ulukutlu L, Yıldız İ. Improved prognosis in ALL with modified BFM protocols-Preliminary results from Turkey. Haematol Blood Transfus 1994; 36: 347- 51.
159. Ercan TE, Soycan LY, Apak H, et al. Antibody titers and immune response to diphteria-tetanus-pertussis and measles-mumps- rubella vaccination in children treated for acute lymphoblastic leukemia. J Ped Hem/Oncol 2005; 27: 273- 7.