title: Disruption of learning processes by chemotherapeutic agents in childhood survivors of acute lymphoblastic leukemia and preclinical models.
abstract: OBJECTIVE
  With the survival rate of acute lymphoblastic leukemia (ALL) surpassing 90 percent within this decade, new research is emerging in the field of late effects. A review of the research investigating the relationship of treatment regimens for ALL to specific late effect deficits, underlying mechanisms, and possible remediation is warranted to support continued studies.
  
  
  METHODS
  The clinical literature was briefly surveyed to describe the occurrence and topography of late effects, specifically neurocognitive deficits. Additionally, the preclinical literature was reviewed to uncover potential underlying mechanisms of these deficits. The advantages of using rodent models to answer these questions are outlined, as is an assessment of the limited number of rodent models of childhood cancer treatment.
  
  
  RESULTS
  The literature supports that childhood survivors of ALL exhibit academic difficulties and are more likely to be placed in a special education program. Behavioral evidence has highlighted impairments in the areas of attention, working memory, and processing speed, leading to a decrease in full scale IQ. Neurophysiological and preclinical evidence for these deficits has implicated white matter abnormalities and acquired brain damage resulting from specific chemotherapeutic agents commonly used during treatment.
  
  
  CONCLUSIONS
  The exact role of chemotherapeutic agents in learning deficits remains mostly unknown. Recommendations for an improved rodent model of learning deficits in childhood cancer survivors are proposed, along with suggestions for future directions in this area of research, in hopes that forthcoming treatment regimens will reduce or eliminate these types of impairments.
authors: 1. Neuroscience Program, Temple University, Philadelphia, PA 19122, USA.
authors: Emily B
authors: EB
authors: Bisen-Hersh
authors: Philip N
authors: PN
authors: Hineline
authors: Ellen A
authors: EA
authors: Walker
references: Metab Brain Dis. 2008 Sep;23(3):325-33
references: 18690526
references: Pediatr Blood Cancer. 2007 Jul;49(1):65-73
references: 16628558
references: Cancer. 2009 Sep 15;115(18):4238-45
references: 19536898
references: Lancet. 1994 Jul 23;344(8917):224-7
references: 7913156
references: Cancer. 1986 Apr 15;57(8):1473-82
references: 3948128
references: Am J Med. 1981 Jul;71(1):47-52
references: 6941699
references: Behav Brain Res. 2008 Jan 25;186(2):168-75
references: 17854921
references: Cancer. 2008 May 1;112(9):2071-9
references: 18327823
references: Ment Retard Dev Disabil Res Rev. 2006;12(3):184-91
references: 17061287
references: Nat Rev Cancer. 2007 Mar;7(3):192-201
references: 17318212
references: Can J Physiol Pharmacol. 2002 Nov;80(11):1076-84
references: 12489927
references: Psychopharmacology (Berl). 2011 May;215(1):105-15
references: 21181126
references: Behav Brain Res. 1998 Apr;92(1):21-30
references: 9588682
references: Pharmacol Biochem Behav. 2009 Dec;94(2):239-43
references: 19747935
references: Ann Oncol. 2008 Apr;19(4):623-9
references: 17974553
references: Pediatr Rehabil. 2004 Jan-Mar;7(1):1-14; discussion 15-6
references: 14744668
references: Pediatr Res. 1994 Feb;35(2):171-8
references: 8165051
references: J Clin Pharm Ther. 2006 Apr;31(2):129-38
references: 16635046
references: Cancer. 2010 Oct 1;116(19):4638-45
references: 20572038
references: Arch Dis Child. 1999 Apr;80(4):318-23
references: 10086934
references: Med Pediatr Oncol. 1989;17(3):216-21
references: 2787469
references: Brain Res Bull. 2008 Nov 25;77(5):237-40
references: 18755251
references: Neuropediatrics. 1989 Nov;20(4):196-8
references: 2608164
references: Behav Brain Res. 2010 Mar 5;207(2):265-72
references: 19840821
references: Pediatr Blood Cancer. 2009 Apr;52(4):447-54
references: 19061221
references: Leukemia. 2000 Jul;14(7):1185-90
references: 10914540
references: Curr Protoc Neurosci. 2003 May;Chapter 8:Unit 8.5E
references: 18428586
references: N Engl J Med. 2006 Oct 12;355(15):1572-82
references: 17035650
references: Behav Brain Res. 2010 May 1;209(1):66-72
references: 20096731
references: Adv Exp Med Biol. 2010;678:vii-viii
references: 20737998
references: Dev Disabil Res Rev. 2008;14(3):185-95
references: 18924154
references: Behav Brain Res. 2010 Mar 17;208(1):112-7
references: 19914299
references: Arch Clin Neuropsychol. 2000 Oct;15(7):603-30
references: 14590198
references: Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):19-31
references: 12732220
references: JAMA. 1994 Nov 9;272(18):1427-32
references: 7933424
references: J Clin Oncol. 1991 Aug;9(8):1348-56
references: 2072138
references: Expert Rev Hematol. 2010 Dec;3(6):655-9
references: 21091140
references: Cancer. 2008 Oct 15;113(8):2188-97
references: 18792068
references: J Pediatr. 2008 Jan;152(1):101-5
references: 18154909
references: J Pediatr. 1992 Dec;121(6):885-9
references: 1447650
references: N Engl J Med. 2009 Jun 25;360(26):2730-41
references: 19553647
references: Arch Dis Child. 2000 May;82(5):353-7
references: 10799421
references: J Pediatr Hematol Oncol. 2000 May-Jun;22(3):206-13
references: 10864051
references: Psychopharmacology (Berl). 2008 Sep;199(4):527-38
references: 18463849
references: Behav Brain Res. 2007 Jul 19;181(1):168-72
references: 17509697
references: J Clin Oncol. 2006 Aug 20;24(24):3858-64
references: 16921038
references: Behav Neurosci. 1999 Jun;113(3):439-50
references: 10443772
references: Curr Protoc Neurosci. 2004 Feb;Chapter 8:Unit 8.18
references: 18428605
references: N Engl J Med. 2006 Jan 12;354(2):166-78
references: 16407512
references: Neurosci Biobehav Rev. 2011 Jan;35(3):729-41
references: 20869395
references: J Biol. 2006;5(7):22
references: 17125495
references: Neuropsychol Rev. 1991 Jun;2(2):147-77
references: 1844707
references: Cancer Invest. 2010 Jun;28(5):544-53
references: 20014946
references: J Clin Oncol. 1995 Oct;13(10):2490-6
references: 7595698
references: Int J Radiat Oncol Biol Phys. 1992;24(1):49-53
references: 1512162
references: Pediatr Blood Cancer. 2005 Sep;45(3):281-90
references: 15806539
references: J Clin Oncol. 2009 Dec 10;27(35):5986-92
references: 19884541
references: Pediatr Blood Cancer. 2005 May;44(5):478-86
references: 15918215
references: J Neurosci. 1985 May;5(5):1228-32
references: 3998819
references: J Pediatr Psychol. 2001 Jan-Feb;26(1):1-9
references: 11145727
references: Neuroscience. 1999;91(4):1299-313
references: 10391437
references: Klin Padiatr. 1998 Jul-Aug;210(4):200-6
references: 9743953
references: J Clin Oncol. 2009 May 10;27(14):2319-27
references: 19364957
references: J Int Neuropsychol Soc. 2004 Mar;10(2):211-20
references: 15012841
references: Neurology. 1998 Jun;50(6):1535-40
references: 9633691
references: J Child Neurol. 1986 Oct;1(4):351-7
references: 3598135
references: J Dev Behav Pediatr. 1990 Dec;11(6):301-5
references: 2289962
references: Cancer. 2003 May 15;97(10):2512-9
references: 12733151
references: Neurosci Lett. 2009 Apr 10;453(3):170-4
references: 19429028
references: J Clin Oncol. 2007 Nov 1;25(31):4914-21
references: 17971588
references: Ann Univ Mariae Curie Sklodowska Med. 1998;53:81-8
references: 10761231
references: J Pediatr Psychol. 1987 Sep;12(3):395-411
references: 3479548
references: Pharmacol Biochem Behav. 2002 Jan-Feb;71(1-2):269-76
references: 11812532
references: J Pediatr Psychol. 2007 Oct;32(9):1127-39
references: 17569711
references: Neurosci Lett. 2004 Jul 1;364(2):110-3
references: 15196689
references: J Natl Cancer Inst. 2010 Jun 16;102(12):881-93
references: 20458059
references: Physiol Behav. 1995 Nov;58(5):969-73
references: 8577895
references: Pharmacol Biochem Behav. 2006 Sep;85(1):66-75
references: 16935324
references: J Pediatr Psychol. 2010 Mar;35(2):144-55
references: 19465537
references: Childs Brain. 1983;10(4):273-80
references: 6684015
references: Am J Pediatr Hematol Oncol. 1989 Spring;11(1):93-105
references: 2653080
references: Neuropsychology. 2000 Apr;14(2):189-200
references: 10791859
references: J Clin Oncol. 1992 May;10(5):810-7
references: 1569453
references: J Clin Oncol. 2008 Sep 1;26(25):4138-43
references: 18757327
references: Med Pediatr Oncol. 2002 May;38(5):320-8
references: 11979456
references: Brain Res Bull. 2010 Mar 16;81(4-5):472-6
references: 19828128
references: J Clin Oncol. 2006 Nov 20;24(33):5277-82
references: 17088567