Novel transplant strategies for generating graft-versus-leukemia effect in acute myeloid leukemia

被引:11
作者
Parmar, Simrit [1 ]
Fernandez-Vina, Marcelo [1 ]
de Lima, Marcos [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cell Therapy, Houston, TX 77005 USA
关键词
allogeneic stem cell transplant; acute myeloid leukemia; graft-versus-host-disease; graft-versus-leukemia; STEM-CELL TRANSPLANTATION; DONOR LEUKOCYTE INFUSIONS; ACUTE MYELOGENOUS LEUKEMIA; LOW-DOSE AZACITIDINE; T-CELLS; MYELODYSPLASTIC SYNDROME; LYMPHOCYTE INFUSIONS; SURVIVAL ADVANTAGE; ADOPTIVE TRANSFER; PROGENITOR CELLS;
D O I
10.1097/MOH.0b013e328343b858
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review This review summarizes the recent developments in the clinical research and therapeutic applications for prevention and treatment of postallogeneic stem cell transplant (SCT) relapse. Specifically, we address various maneuvers to optimize the graft-versus-leukemia (GVL) effect while preventing graft-versus-host-disease (GVHD). Recent findings Alloreactive natural killer (NK) cells can be recruited to mediate GVL effect by careful mismatching on the killer-cell immunoglobulin-like receptors (KIRs) ligand. Donor posttransplant NK cell infusions have led to remission in poor-risk acute myeloid leukemia (AML). Donor lymphocyte infusions may also be used both prophylactically or at the time of leukemia relapse. Posttransplant hypomethylating agents have emerged as promising therapies to safeguard against relapse. Prevention of GVHD while preserving GVL effect using third-party regulatory T cells is under investigation. Adoptive T-cell transfer against specific leukemic antigens and immunotherapy exploiting the marrow microenvironment seem promising as well. Summary In the setting of allogeneic SCT, cellular and immunotherapy needs to be thoroughly investigated for its potential to fight minimal residual disease. The tight balance between GVL and GVHD needs to be harnessed in an optimal fashion to lead to long-term durable remission.
引用
收藏
页码:98 / 104
页数:7
相关论文
共 56 条
[1]  
Alatrash G, 2010, CANCER TREAT RES, V145, P237, DOI 10.1007/978-0-387-69259-3_14
[2]   Allorestricted cytotoxic T cells specific for human CD45 show potent antileukemic activity [J].
Amrolia, PJ ;
Reid, SD ;
Gao, LQ ;
Schultheis, B ;
Dotti, G ;
Brenner, MK ;
Melo, JV ;
Goldman, JM ;
Stauss, HJ .
BLOOD, 2003, 101 (03) :1007-1014
[3]   Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning [J].
Bethge, WA ;
Hegenbart, U ;
Stuart, MJ ;
Storer, BE ;
Maris, MB ;
Flowers, MED ;
Maloney, DG ;
Chauncey, T ;
Bruno, B ;
Agura, E ;
Forman, SJ ;
Blume, KG ;
Niederwieser, D ;
Storb, R ;
Sandmaier, BM .
BLOOD, 2004, 103 (03) :790-795
[4]  
BORCHERS S, 2010, HUM GENE THER
[5]  
BRUNSTEIN CG, 2010, BLOOD
[6]   CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers [J].
Burger, J. A. ;
Peled, A. .
LEUKEMIA, 2009, 23 (01) :43-52
[7]  
CHAMPLIN DAL, 2010, BLOOD, V116
[8]   Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation [J].
Collins, RH ;
Shpilberg, O ;
Drobyski, WR ;
Porter, DL ;
Giralt, S ;
Champlin, R ;
Goodman, SA ;
Wolff, SN ;
Hu, W ;
Verfaillie, C ;
List, A ;
Dalton, W ;
Ognoskie, N ;
Chetrit, A ;
Antin, JH ;
Nemunaitis, J .
JOURNAL OF CLINICAL ONCOLOGY, 1997, 15 (02) :433-444
[9]   Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia [J].
Cooley, Sarah ;
Weisdorf, Daniel J. ;
Guethlein, Lisbeth A. ;
Klein, John P. ;
Wang, Tao ;
Le, Chap T. ;
Marsh, Steven G. E. ;
Geraghty, Daniel ;
Spellman, Stephen ;
Haagenson, Michael D. ;
Ladner, Martha ;
Trachtenberg, Elizabeth ;
Parham, Peter ;
Miller, Jeffrey S. .
BLOOD, 2010, 116 (14) :2411-2419
[10]   Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia [J].
Cooley, Sarah ;
Trachtenberg, Elizabeth ;
Bergemann, Tracy L. ;
Saeteurn, Koy ;
Klein, John ;
Le, Chap T. ;
Marsh, Steven G. E. ;
Guethlein, Lisbeth A. ;
Parham, Peter ;
Miller, Jeffrey S. ;
Weisdorf, Daniel J. .
BLOOD, 2009, 113 (03) :726-732