T cell depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin.
Antithymocyte globulin (ATG) has been used in allogeneic stem-cell transplantation to prevent graft rejection and graft-versus-host disease (GvHD). Its use, however, has been associated with delayed T-cell reconstitution and prolonged susceptibility to opportunistic infections (OIs) especially in patients undergoing T cell-depleted (TCD) transplantation. Recently, a prospective trial was conducted in 52 adult patients (median age, 47 years) with various hematologic malignancies undergoing TCD transplantation from HLA-matched related donors without the use of ATG. The cytoreductive regimen consisted of hyperfractionated total body irradiation (HFTBI), thiotepa, and fludarabine. The preferred source of the graft was peripheral blood stem cells (PBSCs). No additional graft rejection or GvHD prophylaxis was given. All evaluable patients engrafted without any immune-mediated graft rejections. Disease-free survival (DFS) at 3 years was 61% in all patients, and 70% in patients with standard-risk disease. Acute GvHD was limited to grade 2 in 8% and chronic GvHD in 9% of patients. Life-threatening OIs occurred in 3 of 52 patients and was fatal in 1. This study demonstrates durable engraftment with a low incidence of GvHD despite the lack of ATG, as well as the curative potential of this regimen.
Jakubowski
Ann A
AA
Adult Allogeneic Bone Marrow Transplant Service, Division of Hematologic-Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY 10065, USA. jakubowa@mskcc.org
Small
Trudy N
TN
Young
James W
JW
Kernan
Nancy A
NA
Castro-Malaspina
Hugo
H
Hsu
Katherine C
KC
Perales
Miguel-Angel
MA
Collins
Nancy
N
Cisek
Christine
C
Chiu
Michelle
M
van den Brink
Marcel R M
MR
O'Reilly
Richard J
RJ
Papadopoulos
Esperanza B
EB
D000328:Adult; D000961:Antilymphocyte Serum; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D006680:HLA Antigens
J Clin Microbiol. 2000 Feb;38(2):712-5
10655372
Clin Infect Dis. 2004 Dec 1;39(11):1625-32
15578362
Blood. 2001 Dec 1;98(12):3221-7
11719357
Blood. 2002 Aug 1;100(3):761-7
12130483
Blood. 2002 Dec 15;100(13):4325-36
12393746
Blood. 2003 Jan 15;101(2):446-53
12393406
Bone Marrow Transplant. 2003 Jun;31(12):1089-95
12796788
Blood. 2003 Nov 15;102(10):3521-9
12893748
Blood. 2004 Sep 15;104(6):1616-23
15059843
Transplantation. 1974 Oct;18(4):295-304
4153799
Am J Med. 1980 Aug;69(2):204-17
6996481
Int J Radiat Oncol Biol Phys. 1983 Nov;9(11):1607-11
6358154
Blood. 1986 Sep;68(3):770-3
3527302
Blood. 1989 Nov 1;74(6):2227-36
2804361
Blood. 1989 Nov 1;74(6):2237-43
2529927
Blood. 1992 Jun 15;79(12):3380-7
1596577
Immunol Today. 1995 Sep;16(9):437-40
7546208
Immunol Rev. 1997 Jun;157:195-216
9255631
Biol Blood Marrow Transplant. 1997 Jun;3(2):65-75
9267666
Blood. 1998 Feb 1;91(3):1083-90
9446672
J Clin Oncol. 2005 Mar 20;23(9):1993-2003
15774790
Am J Hematol. 2005 Apr;78(4):265-74
15795914
Leukemia. 2005 May;19(5):822-8
15772701
J Clin Oncol. 2005 May 20;23(15):3439-46
15824415
Biol Blood Marrow Transplant. 2005 Jun;11(6):437-47
15931632
J Clin Oncol. 2005 Aug 1;23(22):5074-87
16051954
Biol Blood Marrow Transplant. 2006 Apr;12(4):438-53
16545728
Clin Transplant. 2006 Jan-Feb;20(1):127-31
16556167
Transplantation. 2006 Mar 27;81(6):818-25
16570002
Biol Blood Marrow Transplant. 2006 May;12(5):573-84
16635793
Biol Blood Marrow Transplant. 2006 Jul;12(7):703-11
16785059
J Clin Oncol. 2006 Dec 20;24(36):5695-702
17116940
Blood. 1999 Jan 15;93(2):467-80
9885208
Blood. 1999 Aug 15;94(4):1465-70
10438735
Blood. 2004 Nov 15;104(10):3028-37
15256423
Blood. 2001 Feb 1;97(3):631-7
11157478