Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) accounts for a quarter of malignant neoplasms in children and adolescents. With continuous effort on developing risk-stratified multi-agent chemotherapy through cooperative clinical trials worldwide, survival rate of chi
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Acute Lymphoblastic Leukemia Daisuke Tomizawa and Nobutaka Kiyokawa
Abstract Acute lymphoblastic leukemia (ALL) accounts for a quarter of malignant neoplasms in children and adolescents. With continuous effort on developing risk- stratified multi-agent chemotherapy through cooperative clinical trials worldwide, survival rate of childhood ALL increased from less than 10% in the 1960s to approximately 90% nowadays. Recent advance in genomic analyses is rapidly increasing our understanding of the pathobiology of ALL, which may lead to a development of novel molecular targeted therapy and finally to overcome the disease in future.
2.1 Introduction Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells and the most common type of malignant neoplasms in children and adolescents. Development of multi-agent chemotherapy and risk stratification based on leukemia biology and early treatment response have improved the overall cure rate of childhood ALL to 80% or higher, which is one of the most successful story in the history of human medicine (Table 2.1) [1–12]. In this chapter, advances in the pathobiology and clinical management of ALL in children will be described.
D. Tomizawa, M.D., Ph.D. (*) Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan e-mail: [email protected] N. Kiyokawa, Ph.D. Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan © Springer Nature Singapore Pte Ltd. 2017 E. Ishii (ed.), Hematological Disorders in Children, DOI 10.1007/978-981-10-3886-0_2
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Trial AIEOP-BFM ALL 2000
UKALL 2003
DCOG Protocol ALL-9
EORTC CLG 58591
ALL-2000
Various CCG, POG, and COG trials
Total therapy XV
Study group AIEOP/BFM
MRC
DCOG
EORTC-CLG
NOPHO
COG
SJCRH
2000–2007
2000–2005
2002–2007
1998–2008
1997–2004
2003–2011
Years 2000–2006
ALL subtypes B-ALL T-ALL All B-ALL T-ALL All B-ALL T-ALL All B-ALL T-ALL All B-ALL T-ALL All B-ALL T-ALL All B-ALL T-ALL
Table 2.1 Results of the recently reported trials for pediatric ALL No. of patients 4016 464 3126 2731 388 859 701 90 1947 1650 296 1023 906 115 7153 5982 459 498 422 76 1–18
0–22
1–15
1–18
1–18
1–24
Age 1–18
EFS, % (year) 80.4 (7) 75.9 (7) 87.2 (5) – – 81 (5) 82 (5) 72 (5) 82.7 (5) – – 79 (5) – – – – – 85.6 (5) 86.9 (5) 78.4 (5)
OS, % (year) 91.8 (7) 80.7 (7) 91.5 (5) – – 86 (5) – – 89.7 (5) – – 89 (5) – – 90.4 (5) 91.1 (5) 81.6 (5) 93.5 (5) 94.6 (5) 87.6 (5) Pui et al. [8]
Hunger et al. [7]
Schmiegelow et al. [6]
Domenech et al. [5]
Veerman et al. [4]
Reference Conter et al. [1] Schrappe et al. [2] Vora et al. [3]
34 D. Tomizawa and N. Kiyokawa
Ma-Spore ALL 2003
TCCSG L99-15
Ma-Spore
TCCSG
1999–2003
2002–2011
2005–2010
All B-ALL T-ALL All B-ALL T-ALL All B-ALL T-ALL
551 482 69 556 507 49 754 664 90 1–18
0–18
1–18
85 (5) 85 (5) 87 (5) 80.6 (6) 80.7 (6) 80.5 (6) 78.2 (4) 80.5 (4) 66.0 (4)
91 (5) 91 (5) 91 (5) 88.4 (6) – – 87.6 (4) – – Hasegawa et al. [11] Manabe et
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