title: Immunreconstitution and infectious complications after rituximab treatment in children and adolescents: what do we know and what can we learn from adults?
abstract: Rituximab, an anti CD20 monoclonal antibody, is widely used in the treatment of B-cell malignancies in adults and increasingly in pediatric patients. By depleting B-cells, rituximab interferes with humoral immunity. This review provides a comprehensive overview of immune reconstitution and infectious complications after rituximab treatment in children and adolescents. Immune reconstitution starts usually after six months with recovery to normal between nine to twelve months. Extended rituximab treatment results in a prolonged recovery of B-cells without an increase of clinically relevant infections. The kinetic of B-cell recovery is influenced by the concomitant chemotherapy and the underlying disease. Intensive B-NHL treatment such as high-dose chemotherapy followed by rituximab bears a risk for prolonged hypogammaglobulinemia. Overall transient alteration of immune reconstitution and infections after rituximab treatment are acceptable for children and adolescent without significant differences compared to adults. However, age related disparities in the kinetic of immune reconstitution and the definitive role of rituximab in the treatment for children and adolescents with B-cell malignancies need to be evaluated in prospective controlled clinical trials.
authors: Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, 48149, Germany. jennifer.worch@ukmuenster.de.
authors: Jennifer
authors: J
authors: Worch
authors: Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, 48149, Germany. olga.makarova@ukmuenster.de.
authors: Olga
authors: O
authors: Makarova
authors: Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, 48149, Germany. birgit.burkhardt@ukmuenster.de.
authors: Birgit
authors: B
authors: Burkhardt
references: Pediatr Nephrol. 2009 Jul;24(7):1321-8
references: 19421786
references: J Clin Immunol. 2007 May;27(3):339-46
references: 17345151
references: Cancer Immunol Immunother. 2000 Mar;48(12):673-83
references: 10752475
references: Blood. 2002 Sep 15;100(6):2257-9
references: 12200395
references: Semin Hematol. 2010 Apr;47(2):187-98
references: 20350666
references: Leukemia. 2013 Apr;27(5):1174-7
references: 22940833
references: Am J Transplant. 2008 Dec;8(12):2607-17
references: 18808404
references: Cancer Treat Rev. 2013 Oct;39(6):632-9
references: 23219151
references: Curr Opin Pediatr. 2008 Feb;20(1):17-22
references: 18197034
references: Arthritis Rheum. 2010 Jan;62(1):64-74
references: 20039397
references: J Pediatr. 2005 Feb;146(2):217-21
references: 15689912
references: Pediatr Nephrol. 2010 Jun;25(6):1109-15
references: 20238230
references: Bone Marrow Transplant. 2009 May;43(9):679-84
references: 19029962
references: Blood. 2008 Oct 15;112(8):3312-21
references: 18689543
references: Br J Haematol. 2007 May;137(4):349-54
references: 17456057
references: Eur J Haematol. 2003 Apr;70(4):225-30
references: 12656745
references: Lancet. 2001 Nov 3;358(9292):1511-3
references: 11705566
references: Ann Oncol. 1999 Jun;10(6):655-61
references: 10442187
references: Blood. 2005 Feb 1;105(3):948-58
references: 15486066
references: Blood. 2004 Jun 15;103(12):4416-23
references: 14976046
references: Vaccine. 2010 Apr 26;28(19):3278-84
references: 20226246
references: Bone Marrow Transplant. 2009 May;43(9):701-8
references: 19029963
references: J Pediatr Hematol Oncol. 2014 Jul;36(5):395-401
references: 23823112
references: Pediatr Blood Cancer. 2009 Feb;52(2):177-81
references: 18816698
references: Hematol Oncol. 2011 Mar;29(1):5-9
references: 20552573
references: Blood. 2006 Apr 1;107(7):2639-42
references: 16352811
references: Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):16-8
references: 14734446
references: Leuk Lymphoma. 2008 Jan;49(1):152-3
references: 18203024
references: Ann Hematol. 2010 May;89(5):519-22
references: 19727726
references: Br J Haematol. 2014 Nov;167(3):394-401
references: 25066629
references: Eur J Pediatr. 2007 Jan;166(1):85-6
references: 16896642
references: Clin Lymphoma Myeloma Leuk. 2013 Apr;13(2):106-11
references: 23276889
references: Blood. 2007 Apr 1;109(7):2736-43
references: 17138821
references: J Clin Oncol. 2005 Mar 20;23(9):1984-92
references: 15668467
references: Eur J Haematol. 2005 May;74(5):442-4
references: 15813920
references: Pathol Oncol Res. 2014 Jul;20(3):649-54
references: 24488335
references: Bone Marrow Transplant. 2008 Oct;42(7):483-7
references: 18695668
references: Bone Marrow Transplant. 2006 Sep;38(6):433-6
references: 16892074
references: J Pediatr Hematol Oncol. 2012 May;34(4):271-5
references: 22430582
references: Lupus. 2015 Jan;24(1):10-7
references: 25117653
references: Bone Marrow Transplant. 2005 Jan;35(2):207-8
references: 15531902
references: Immunol Lett. 2014 May-Jun;159(1-2):76-8
references: 24184906
references: Blood. 2002 Feb 15;99(4):1486-8
references: 11830505
references: Leuk Lymphoma. 2009 Mar;50(3):323-4
references: 19347724
references: Leuk Lymphoma. 2009 Feb;50(2):211-5
references: 19197729
references: Neurology. 2014 Jul 8;83(2):142-50
references: 24920861
references: Leuk Lymphoma. 2009 Jul;50(7):1083-95
references: 19399690
references: MAbs. 2013 Nov-Dec;5(6):826-37
references: 23933992
references: Int J Infect Dis. 2011 Jan;15(1):e2-16
references: 21074471
references: J Clin Oncol. 2006 Jul 1;24(19):3121-7
references: 16754935
references: Blood. 2005 Dec 1;106(12):3725-32
references: 16123223
references: Blood. 1999 Nov 15;94(10):3294-306
references: 10552938
references: Eur J Haematol. 2006 Sep;77(3):226-32
references: 16923109
references: J Natl Cancer Inst. 2007 May 2;99(9):706-14
references: 17470738
references: Blood. 2008 Feb 1;111(3):1456-63
references: 18024795
references: Arthritis Rheum. 2008 Jan;58(1):5-14
references: 18163518
references: Ann Oncol. 2012 Feb;23(2):450-7
references: 21576285
references: Bone Marrow Transplant. 2004 Jan;33(1):129-30
references: 14647260
references: Blood. 2004 Feb 1;103(3):777-83
references: 12907446
references: Blood. 2002 Jun 15;99(12):4364-9
references: 12036863
references: Blood. 2000 Feb 15;95(4):1502-5
references: 10666232
references: Ann Hematol. 2008 May;87(5):405-12
references: 18064459
references: Blood. 2005 Sep 1;106(5):1538-43
references: 15914552
references: Blood. 2004 Nov 15;104(10):3064-71
references: 15284112
references: Am J Cancer Res. 2012;2(6):676-90
references: 23226614
references: J Immunol. 2011 May 15;186(10):6044-55
references: 21498665
references: Ann Rheum Dis. 2008 Jul;67(7):937-41
references: 17981914
references: Vaccine. 2006 Nov 10;24(44-46):6620-3
references: 16870313
references: Acta Paediatr. 1995 Feb;84(2):177-82
references: 7756804
references: Clin Immunol. 2001 Feb;98(2):175-9
references: 11161973
references: Am J Transplant. 2005 Jan;5(1):50-7
references: 15636611
references: Blood. 2003 May 15;101(10):3857-61
references: 12531800
references: Oncologist. 2010;15(11):1214-9
references: 21041380
references: Arthritis Rheum. 2007 Sep;56(9):3044-56
references: 17763423
references: Int Immunol. 2012 Aug;24(8):477-83
references: 22438420
references: Ann Oncol. 2005 Oct;16(10):1675-82
references: 16030029
references: Leuk Lymphoma. 2007 Jul;48(7):1307-12
references: 17613758
references: Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2011 Jun;19(3):676-9
references: 21729548
references: J Pediatr. 2006 May;148(5):623-627
references: 16737873
references: Pediatr Blood Cancer. 2008 Apr;50(4):822-5
references: 17570702
references: PLoS One. 2012;7(5):e36698
references: 22666325
references: Int J Hematol. 2008 Nov;88(4):443-7
references: 18855101
references: N Engl J Med. 2002 Jan 24;346(4):235-42
references: 11807147
references: Blood. 2010 Oct 28;116(17):3372-3; author reply 3373-4
references: 21030571
references: Arthritis Rheum. 2010 Jan;62(1):75-81
references: 20039396
references: J Pediatr Hematol Oncol. 2004 Nov;26(11):727-34
references: 15543007
references: J Natl Cancer Inst. 2009 Feb 18;101(4):248-55
references: 19211444
references: Med J Aust. 1977 Feb 26;1(9):292-4
references: 859489
references: Blood. 2011 Dec 22;118(26):6769-71
references: 22058114
references: J Hematother Stem Cell Res. 2003 Feb;12(1):9-10
references: 12662431
references: Ann Hematol. 2008 Apr;87(4):285-9
references: 17943285
references: J Pediatr. 2013 Jun;162(6):1252-8, 1258.e1
references: 23269206
references: J Clin Oncol. 1998 Aug;16(8):2825-33
references: 9704735
references: Lancet Oncol. 2006 May;7(5):379-91
references: 16648042
references: Cancer. 2007 Jun 1;109 (11):2182-9
references: 17429839
references: J Clin Oncol. 2010 Jul 1;28(19):3115-21
references: 20516455