title: Cellular therapies in acute lymphoblastic leukemia.
abstract: ALL remains a difficult disease to treat. In the adult setting, most patients will ultimately die of their disease, whereas in the pediatric setting, relapsed and refractory disease remains a therapeutic challenge. Cellular therapy through allo-HSCT remains an option for these patients, and recent advances in alternative forms of allo-HSCT, including unrelated donor transplants, UCB transplants, and haploidentical transplants, have expanded the numbers of patients eligible for allo-HSCT but have not improved outcomes when compared with HLA-matched related allo-HSCTs. In light of this persistent failure, several novel adoptive cellular approaches are being investigated to treat patients with ALL. The use of enriched WT-1–specific donor T cells to treat patients with ALL is currently under investigation in phase I trials at several centers. Treatment of ALL with genetically modified T cells targeted to the CD19 antigen through the expression of a CD19-specific CAR also have entered phase I clinical trials at several centers. Similarly, a clinical trial treating patients with ALL with genetically modified NK cells targeted to the CD19 antigen has recently opened for accrual. Collectively, these ongoing and anticipated trials provide a promising role for adoptive cellular therapies in the treatment of ALL. What remains to be seen is whether this promise will either translate into improved outcomes for these patients or provide significant insights on which to design second-generation adoptive cell therapeutic clinical trials for ALL in the future.
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 569, New York, NY 10065, USA.
authors.forename: Jae H
authors.initials: JH
authors.lastname: Park
authors.forename: Craig
authors.initials: C
authors.lastname: Sauter
authors.forename: Renier
authors.initials: R
authors.lastname: Brentjens
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017690:Cell Transplantation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D019172:Transplantation Conditioning
references.citation: Mol Ther. 2009 Apr;17(4):742-9
references.pmid: 19209146
references.citation: Bone Marrow Transplant. 2008 Mar;41(5):473-81
references.pmid: 18176612
references.citation: Blood. 2003 Oct 15;102(8):3068-70
references.pmid: 12842984
references.citation: Blood. 2004 Feb 1;103(3):767-76
references.pmid: 12958064
references.citation: Nat Rev Cancer. 2003 Jan;3(1):35-45
references.pmid: 12509765
references.citation: Best Pract Res Clin Haematol. 2008 Sep;21(3):467-83
references.pmid: 18790450
references.citation: Blood. 2007 Feb 1;109(3):944-50
references.pmid: 17032921
references.citation: J Immunother. 2009 Sep;32(7):689-702
references.pmid: 19561539
references.citation: Nat Immunol. 2002 Nov;3(11):999-1005
references.pmid: 12407407
references.citation: Cancer Res. 2006 Nov 15;66(22):10995-1004
references.pmid: 17108138
references.citation: Blood. 2010 Apr 1;115(13):2695-703
references.pmid: 20110422
references.citation: Haematologica. 2011 Aug;96(8):1113-20
references.pmid: 21508120
references.citation: N Engl J Med. 2011 Aug 25;365(8):725-33
references.pmid: 21830940
references.citation: Curr Oncol Rep. 2004 Sep;6(5):339-47
references.pmid: 15291974
references.citation: Cancer Gene Ther. 2010 Mar;17(3):147-54
references.pmid: 19745843
references.citation: Blood. 2010 Nov 25;116(22):4439-43
references.pmid: 20716774
references.citation: Blood. 2003 Aug 1;102(3):1131-7
references.pmid: 12689945
references.citation: Mol Ther. 2009 Aug;17(8):1453-64
references.pmid: 19384291
references.citation: Blood. 2007 Feb 15;109(4):1408-13
references.pmid: 17062730
references.citation: Haematologica. 2003 May;88(5):555-60
references.pmid: 12745275
references.citation: Blood. 2009 May 7;113(19):4489-96
references.pmid: 19244158
references.citation: Blood. 2002 Mar 15;99(6):2009-16
references.pmid: 11877273
references.citation: Blood. 2010 Jul 22;116(3):366-74
references.pmid: 20404137
references.citation: Bone Marrow Transplant. 2007 Aug;40(4):339-47
references.pmid: 17572712
references.citation: Blood. 2007 Oct 15;110(8):3064-70
references.pmid: 17569820
references.citation: J Clin Oncol. 2009 Feb 20;27(6):911-8
references.pmid: 19124805
references.citation: J Clin Oncol. 2004 Jul 15;22(14):2816-25
references.pmid: 15254049
references.citation: Blood Cells Mol Dis. 2004 Jul-Aug;33(1):83-9
references.pmid: 15223016
references.citation: Sci Transl Med. 2011 Aug 10;3(95):95ra73
references.pmid: 21832238
references.citation: Curr Opin Immunol. 2009 Apr;21(2):215-23
references.pmid: 19327974
references.citation: Nat Med. 2003 Mar;9(3):279-86
references.pmid: 12579196
references.citation: Leukemia. 2010 Jun;24(6):1160-70
references.pmid: 20428207
references.citation: Blood. 2009 Feb 19;113(8):1631-8
references.pmid: 19104080
references.citation: Blood. 2005 Feb 1;105(3):1343-7
references.pmid: 15466923
references.citation: Br J Haematol. 2005 Dec;131(5):579-87
references.pmid: 16351633
references.citation: Blood. 2011 Nov 3;118(18):4817-28
references.pmid: 21849486
references.citation: Blood. 2005 Nov 1;106(9):3062-7
references.pmid: 16020516
references.citation: Blood. 2001 Feb 15;97(4):835-43
references.pmid: 11159505
references.citation: Hematol Oncol Clin North Am. 2000 Dec;14(6):1353-66, x
references.pmid: 11147227
references.citation: N Engl J Med. 1979 May 10;300(19):1068-73
references.pmid: 34792
references.citation: N Engl J Med. 2004 Nov 25;351(22):2265-75
references.pmid: 15564543
references.citation: Blood. 1998 Nov 15;92(10):3515-20
references.pmid: 9808542
references.citation: Blood. 1993 Jan 1;81(1):249-53
references.pmid: 8417795
references.citation: Leukemia. 2007 Sep;21(9):1907-14
references.pmid: 17611565
references.citation: Leukemia. 2002 Dec;16(12):2423-8
references.pmid: 12454748
references.citation: Biol Blood Marrow Transplant. 2009 Feb;15(2):257-65
references.pmid: 19167686
references.citation: Blood. 2010 Nov 18;116(20):4368-75
references.pmid: 20664060
references.citation: Blood. 1994 Dec 1;84(11):3948-55
references.pmid: 7524753
references.citation: Bone Marrow Transplant. 2008 Mar;41(5):483-93
references.pmid: 18026156
references.citation: Blood. 2009 Jul 16;114(3):535-46
references.pmid: 19451549
references.citation: N Engl J Med. 1998 Oct 22;339(17):1186-93
references.pmid: 9780338
references.citation: Ann Intern Med. 1993 Aug 1;119(3):207-14
references.pmid: 8391772
references.citation: Cancer. 2008 Dec 1;113(11):3186-91
references.pmid: 18846563
references.citation: Science. 2002 Mar 15;295(5562):2097-100
references.pmid: 11896281
references.citation: Bone Marrow Transplant. 2005 Jul;36(2):163-9
references.pmid: 15937507
references.citation: Blood. 2006 Feb 1;107(3):1116-23
references.pmid: 16195338
references.citation: Bone Marrow Transplant. 2000 Sep;26(5):511-6
references.pmid: 11019840
references.citation: Leukemia. 2006 Oct;20(10):1819-28
references.pmid: 16932339
references.citation: Cancer. 2011 Apr 15;117(8):1583-94
references.pmid: 21472706
references.citation: Biol Blood Marrow Transplant. 2011 Sep;17(9):1335-42
references.pmid: 21232623
references.citation: Blood. 2006 Feb 15;107(4):1325-31
references.pmid: 16269610
references.citation: Biol Blood Marrow Transplant. 2008 Dec;14(12):1394-400
references.pmid: 19041062
references.citation: N Engl J Med. 2006 Jan 12;354(2):166-78
references.pmid: 16407512
references.citation: Leukemia. 2004 Apr;18(4):676-84
references.pmid: 14961035
references.citation: Bone Marrow Transplant. 2011 Mar;46(3):323-9
references.pmid: 21042314
references.citation: Lancet. 2008 Mar 22;371(9617):1030-43
references.pmid: 18358930
references.citation: Stem Cell Rev. 2006;2(2):81-6
references.pmid: 17237545
references.citation: Blood. 2005 Jul 1;106(1):376-83
references.pmid: 15755898
references.citation: Immunogenetics. 2000 Feb;51(2):99-107
references.pmid: 10663572
references.citation: Leukemia. 2011 Jan;25(1):41-7
references.pmid: 20944676
references.citation: Biol Blood Marrow Transplant. 2009 Jan;15(1 Suppl):154-61
references.pmid: 19147098
references.citation: Lancet Oncol. 2010 Jul;11(7):653-60
references.pmid: 20558104
references.citation: Biol Blood Marrow Transplant. 2009 Nov;15(11):1407-14
references.pmid: 19822300
references.citation: J Immunol. 2000 Feb 15;164(4):1873-80
references.pmid: 10657636
references.citation: Hum Gene Ther. 2007 Aug;18(8):712-25
references.pmid: 17685852
references.citation: Blood. 1995 Sep 1;86(5):2041-50
references.pmid: 7655033
references.citation: N Engl J Med. 2010 Nov 25;363(22):2091-101
references.pmid: 21105791
references.citation: Blood. 2008 Nov 1;112(9):3574-81
references.pmid: 18606875
references.citation: Cancer Res. 2009 May 1;69(9):4010-7
references.pmid: 19383914
references.citation: Cancer. 2006 Jun 15;106(12):2657-63
references.pmid: 16703597
references.citation: J Clin Oncol. 2004 Oct 15;22(20):4075-86
references.pmid: 15353542
references.citation: Biol Blood Marrow Transplant. 2006 Jan;12(1):1-30
references.pmid: 16399566
references.citation: Blood. 1999 Jan 15;93(2):467-80
references.pmid: 9885208
references.citation: Blood. 2004 Dec 1;104(12):3813-20
references.pmid: 15280199
references.citation: Blood. 2006 Apr 1;107(7):2643-52
references.pmid: 16352804
references.citation: Blood. 2011 Feb 24;117(8):2332-9
references.pmid: 21149636
references.citation: Blood. 2009 Apr 30;113(18):4153-62
references.pmid: 19141862
references.citation: Blood. 2009 Mar 26;113(13):2902-5
references.pmid: 19179301
references.citation: Bone Marrow Transplant. 2006 Jan;37(2):155-63
references.pmid: 16284608
references.citation: J Immunother. 2009 Feb-Mar;32(2):169-80
references.pmid: 19238016
references.citation: J Clin Oncol. 2011 Jun 20;29(18):2493-8
references.pmid: 21576633
references.citation: Haematologica. 2009 Oct;94(10):1399-406
references.pmid: 19648167
references.citation: Cancer Res. 2011 May 15;71(10):3516-27
references.pmid: 21558388
references.citation: Blood. 2008 Feb 15;111(4):1827-33
references.pmid: 18048644
references.citation: Science. 2006 Oct 6;314(5796):126-9
references.pmid: 16946036
references.citation: Discov Med. 2010 Apr;9(47):277-88
references.pmid: 20423671
references.citation: Hum Gene Ther. 2010 Jan;21(1):75-86
references.pmid: 19719389
references.citation: Annu Rev Med. 1999;50:369-86
references.pmid: 10073284
references.citation: Curr Opin Hematol. 2008 Nov;15(6):568-75
references.pmid: 18832927
references.citation: Cancer Res. 2011 Sep 1;71(17):5697-706
references.pmid: 21742772
references.citation: Blood. 2007 Sep 15;110(6):1924-32
references.pmid: 17505014
references.citation: Blood. 2003 Feb 15;101(4):1637-44
references.pmid: 12393484
references.citation: Blood. 2010 Nov 18;116(20):4099-102
references.pmid: 20668228
references.citation: Bone Marrow Transplant. 2008 Aug;42 Suppl 1:S18-S24
references.pmid: 18724292
references.citation: J Clin Oncol. 2006 Dec 20;24(36):5695-702
references.pmid: 17116940
references.citation: Blood. 2005 Feb 15;105(4):1622-31
references.pmid: 15507526
references.citation: Blood. 2009 Nov 5;114(19):4293-9
references.pmid: 19706886
references.citation: Biol Blood Marrow Transplant. 2011 Jan;17(1 Suppl):S89-93
references.pmid: 21195317
references.citation: J Clin Oncol. 2005 May 20;23(15):3447-54
references.pmid: 15753458
references.citation: N Engl J Med. 2004 Nov 25;351(22):2276-85
references.pmid: 15564544
references.citation: Haematologica. 2005 Oct;90(10):1346-56
references.pmid: 16219571
references.citation: Leukemia. 2010 Jul;24(7):1276-82
references.pmid: 20485378
references.citation: Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5426-35
references.pmid: 17855649
references.citation: Semin Hematol. 2009 Jan;46(1):64-75
references.pmid: 19100369