title: Therapeutic options in post-transplant lymphoproliferative disorders.
abstract: Post-transplantation lymphoproliferative disorders (PTLD) are the second most frequent malignancies after solid organ transplantation and cover a wide spectrum ranging from polyclonal early lesions to monomorphic lymphoma. Available treatment modalities include immunosuppression reduction, immunotherapy with anti-B-cell monoclonal antibodies, chemotherapy, antiviral therapy, cytotoxic T-cell therapy as well as surgery and irradiation. Owing to the small number of cases and the heterogeneity of PTLD, current treatment strategies are mostly based on case reports and small, often retrospective studies. Moreover, many studies on the treatment of PTLD have involved a combination of different treatment options, complicating the evaluation of individual treatment components. However, there has been significant progress over the last few years. Three prospective phase II trials on the efficacy of rituximab monotherapy have shown significant complete remission rates without any relevant toxicity. A prospective, multicenter, international phase II trial evaluating sequential treatment with rituximab and CHOP-based chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) is ongoing and preliminary results have been promising. Cytotoxic T-cell therapy targeting Epstein-Barr virus (EBV)-infected B cells has shown low toxicity and high efficacy in a phase II trial and will be a future therapeutic option at specialized centers. Here, we review the currently available data on the different treatment modalities with a focus on PTLD following solid organ transplantation in adult patients.
authors.forename: Heiner
authors.initials: H
authors.lastname: Zimmermann
authors.forename: Ralf Ulrich
authors.initials: RU
authors.lastname: Trappe
keywords: CHOP; antiviral therapy; cytotoxic T-cells; immunosuppression reduction; interferon alpha; post-transplant lymphoproliferative disorders (PTLD); rituximab; treatment
references.citation: Med Oncol. 2004;21(3):273-84
references.pmid: 15456956
references.citation: Transplantation. 1994 Jun 27;57(12):1813-5
references.pmid: 8016889
references.citation: Transplantation. 2008 Jul 27;86(2):215-22
references.pmid: 18645482
references.citation: Transplantation. 2001 Jan 15;71(1):47-52
references.pmid: 11211194
references.citation: J Clin Oncol. 2010 Sep 20;28(27):4184-90
references.pmid: 20660832
references.citation: J Heart Lung Transplant. 2001 Oct;20(10):1054-63
references.pmid: 11595560
references.citation: Transplantation. 1998 Dec 27;66(12):1770-9
references.pmid: 9884275
references.citation: Cancer. 2010 Feb 15;116(4):863-70
references.pmid: 20052713
references.citation: Clin Cancer Res. 2011 Jan 1;17(1):19-30
references.pmid: 21208903
references.citation: Blood. 1994 Aug 1;84(3):972-84
references.pmid: 8043879
references.citation: Am J Transplant. 2009 Oct;9(10):2331-7
references.pmid: 19663889
references.citation: J Infect Dis. 2000 Jun;181(6):2050-4
references.pmid: 10837191
references.citation: Transpl Infect Dis. 2004 Mar;6(1):15-22
references.pmid: 15225222
references.citation: Transplantation. 2007 Jun 15;83(11):1423-8
references.pmid: 17565314
references.citation: N Engl J Med. 1998 May 14;338(20):1413-21
references.pmid: 9580648
references.citation: Chest. 2003 Oct;124(4):1242-9
references.pmid: 14555552
references.citation: Ann Hematol. 2007 Aug;86(8):599-607
references.pmid: 17522862
references.citation: J Am Soc Nephrol. 1997 Sep;8(9):1483-9
references.pmid: 9294843
references.citation: Cancer. 1993 Nov 1;72(9):2782-5
references.pmid: 8402504
references.citation: Cancer. 2005 Oct 15;104(8):1661-7
references.pmid: 16149091
references.citation: J Heart Lung Transplant. 2003 May;22(5):505-14
references.pmid: 12742411
references.citation: Transpl Infect Dis. 2001 Jun;3(2):79-87
references.pmid: 11395973
references.citation: Transplantation. 2001 Apr 27;71(8):1065-8
references.pmid: 11374404
references.citation: Lancet. 2006 Jan 21;367(9506):233-9
references.pmid: 16427492
references.citation: J Clin Microbiol. 1997 Jun;35(6):1612-5
references.pmid: 9163497
references.citation: Transplantation. 1995 Sep 27;60(6):547-54
references.pmid: 7570949
references.citation: Am J Transplant. 2011 Feb;11(2):336-47
references.pmid: 21219573
references.citation: Blood. 2001 Mar 15;97(6):1590-7
references.pmid: 11238096
references.citation: J Infect Dis. 1979 May;139(5):553-8
references.pmid: 220340
references.citation: J Clin Pharmacol. 2005 Jul;45(7):792-801
references.pmid: 15951469
references.citation: J Clin Oncol. 2010 Feb 20;28(6):1038-46
references.pmid: 20085936
references.citation: Transplantation. 2001 Apr 27;71(8):1076-88
references.pmid: 11374406
references.citation: J Exp Med. 1999 Aug 16;190(4):567-76
references.pmid: 10449527
references.citation: J Immunol Methods. 1994 Dec 28;177(1-2):101-11
references.pmid: 7822816
references.citation: Transplantation. 2006 Aug 15;82(3):375-81
references.pmid: 16906036
references.citation: Ann Surg. 2002 Oct;236(4):429-36; discussion 436-7
references.pmid: 12368671
references.citation: Blood. 2001 Sep 1;98(5):1332-8
references.pmid: 11520779
references.citation: Transplantation. 2003 Mar 27;75(6):851-6
references.pmid: 12660514
references.citation: Transplantation. 2003 Sep 27;76(6):984-8
references.pmid: 14508366
references.citation: Pediatr Transplant. 2003 Aug;7(4):305-14
references.pmid: 12890010
references.citation: Hepatology. 2000 Mar;31(3):808-9
references.pmid: 10722316
references.citation: Transplantation. 2007 Dec 27;84(12):1708-12
references.pmid: 18165786
references.citation: Am J Transplant. 2006 May;6(5 Pt 1):1017-24
references.pmid: 16611339
references.citation: Transplantation. 2002 Oct 27;74(8):1103-9
references.pmid: 12438954
references.citation: Hepatogastroenterology. 2000 Jan-Feb;47(31):211-9
references.pmid: 10690611
references.citation: Transplant Proc. 1969 Mar;1(1):106-12
references.pmid: 4944206
references.citation: Ann Oncol. 2000;11 Suppl 1:45-8
references.pmid: 10707778
references.citation: Ann Hematol. 2009 Feb;88(2):167-72
references.pmid: 18636261
references.citation: Blood. 2006 Apr 15;107(8):3053-7
references.pmid: 16254143
references.citation: Pediatr Transplant. 2001 Jun;5(3):198-203
references.pmid: 11422823
references.citation: Pediatr Transplant. 2007 Feb;11(1):58-65
references.pmid: 17239124
references.citation: Br J Haematol. 2006 Sep;134(6):602-12
references.pmid: 16889621
references.citation: Mod Pathol. 2002 Jun;15(6):647-56
references.pmid: 12065779
references.citation: Br J Haematol. 2003 Dec;123(5):830-5
references.pmid: 14632773
references.citation: Transplantation. 2007 Apr 15;83(7):912-8
references.pmid: 17460562
references.citation: J Clin Virol. 2004 Sep;31(1):58-65
references.pmid: 15288615
references.citation: Transplantation. 1999 Apr 15;67(7):1068-70
references.pmid: 10221496
references.citation: Lancet. 1984 Mar 17;1(8377):583-7
references.pmid: 6142304
references.citation: Blood. 2009 Apr 16;113(16):3765-72
references.pmid: 19029438
references.citation: Am J Transplant. 2006 Mar;6(3):569-76
references.pmid: 16468968
references.citation: Nat Med. 1996 May;2(5):551-5
references.pmid: 8616714
references.citation: Haematologica. 2007 Feb;92(2):273-4
references.pmid: 17296588
references.citation: Blood. 2000 Dec 15;96(13):4055-63
references.pmid: 11110673
references.citation: Blood. 2007 Aug 15;110(4):1123-31
references.pmid: 17468341
references.citation: Crit Rev Oncol Hematol. 2005 Oct;56(1):87-99
references.pmid: 15979889
references.citation: Lancet. 1995 Jan 7;345(8941):9-13
references.pmid: 7799740
references.citation: Lancet Oncol. 2008 May;9(5):435-44
references.pmid: 18400558
references.citation: Am J Transplant. 2005 Dec;5(12):2901-6
references.pmid: 16303003
references.citation: Blood. 2007 Mar 15;109(6):2571-8
references.pmid: 17119113
references.citation: Haematologica. 2011 Jul;96(7):1067-71
references.pmid: 21719885
references.citation: Abdom Imaging. 2001 Mar-Apr;26(2):200-6
references.pmid: 11178701
references.citation: Transplantation. 1998 Dec 27;66(12):1641-4
references.pmid: 9884252
references.citation: J Clin Oncol. 2000 Nov 1;18(21):3622-32
references.pmid: 11054435
references.citation: Br J Haematol. 2002 Sep;118(4):1120-3
references.pmid: 12199794
references.citation: Haematologica. 2007 Nov;92(11):1489-94
references.pmid: 18024397
references.citation: N Engl J Med. 1989 Oct 19;321(16):1080-5
references.pmid: 2552313
references.citation: J Clin Virol. 2003 Dec;28(3):323-30
references.pmid: 14522071
references.citation: Transplantation. 1998 Feb 15;65(3):397-400
references.pmid: 9484759
references.citation: Br J Surg. 2001 Oct;88(10):1330-4
references.pmid: 11578286
references.citation: Clin Transplant. 1998 Apr;12(2):109-15
references.pmid: 9575398
references.citation: Transplantation. 2002 Sep 15;74(5):656-64
references.pmid: 12352882