Response and toxicity of donor lymphocyte infusions following T-cell depleted non-myeloablative allogeneic hematopoietic SCT from 3-6/6 HLA matched donors

被引:14
作者
Rizzieri, D. A. [1 ]
Dev, P. [1 ]
Long, G. D. [1 ]
Gasparetto, C. [1 ]
Sullivan, K. M. [1 ]
Horwitz, M. L. [1 ]
Chute, J. [1 ]
Chao, N. J. [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Med, Div Cellular Therapy, Durham, NC 27710 USA
关键词
DLI; haploidentical donors; non-myeloablative allogeneic transplantation; leukemia/lymphoma; BONE-MARROW-TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HOST-DISEASE; ADOPTIVE IMMUNOTHERAPY; IMMUNE RECONSTITUTION; CONDITIONING REGIMEN; IN-VIVO; RELAPSE;
D O I
10.1038/bmt.2008.321
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
We report the outcome of early donor lymphocyte infusions (DLIs) after T-cell depleted non-myeloablative transplantation using stem cells from HLA-matched or mismatched donors. Sixty-nine patients with high-risk hematologic malignancies received DLI following fludarabine, CY and alemtuzumab with infusion of stem cells from a matched sibling (52) or partially matched family member donor (17). Patients received the first infusion at a median of 50 days after transplant, and doses ranged from 1 x 10(4) CD3+ cells/kg to 3.27 x 10(8) CD3+ cells/kg, depending on clinical status and the physician's discretion. A median cell dose of 1 x 10(5) CD3+ cells/kg in the mismatched setting and 1 x 10(6) CD3+ cells/kg in the matched sibling setting appears safe with only 1 of 7 (14%) and 4 of 31 patients (13%), respectively, experiencing severe acute GVHD at these doses. Importantly, 38% of patients with persistent disease before DLI attained a remission after infusion. Nine of the 69 patients remain alive and disease-free 32-71 months after the first DLI. In conclusion, low doses of DLI can be safely provided soon after T-cell depleted non-myeloablative therapy and provide a chance of remission. However, long-term survival still remains poor, primarily because of relapse in these patients.
引用
收藏
页码:327 / 333
页数:7
相关论文
共 35 条
  • [1] Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation
    Amrolia, Persis J.
    Muccioli-Casadei, Giada
    Huls, Helen
    Adams, Stuart
    Durett, April
    Gee, Adrian
    Yvon, Eric
    Weiss, Heidi
    Cobbold, Mark
    Gaspar, H. Bobby
    Rooney, Cliona
    Kuehnle, Ingrid
    Ghetie, Victor
    Schindler, John
    Krance, Robert
    Heslop, Helen E.
    Veys, Paul
    Vitetta, Ellen
    Brenner, Malcolm K.
    [J]. BLOOD, 2006, 108 (06) : 1797 - 1808
  • [2] Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype
    Aversa, F
    Tabilio, A
    Velardi, A
    Cunningham, I
    Terenzi, A
    Falzetti, F
    Ruggeri, L
    Barbabietola, G
    Aristei, C
    Latini, P
    Reisner, Y
    Martelli, MF
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (17) : 1186 - 1193
  • [3] Revised response criteria for malignant lymphoma
    Cheson, Bruce D.
    Pfistner, Beate
    Juweid, Malik E.
    Gascoyne, Randy D.
    Specht, Lena
    Horning, Sandra J.
    Coiffier, Bertrand
    Fisher, Richard I.
    Hagenbeek, Anton
    Zucca, Emanuele
    Rosen, Steven T.
    Stroobants, Sigrid
    Lister, T. Andrew
    Hoppe, Richard T.
    Dreyling, Martin
    Tobinai, Kensei
    Vose, Julie M.
    Connors, Joseph M.
    Federico, Massimo
    Diehl, Volker
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (05) : 579 - 586
  • [4] Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation
    de Lima, M
    Anagnostopoulos, A
    Munsell, M
    Shahjahan, M
    Ueno, N
    Ippoliti, C
    Andersson, BS
    Gajewski, J
    Couriel, D
    Cortes, J
    Donato, M
    Neumann, J
    Champlin, R
    Giralt, S
    [J]. BLOOD, 2004, 104 (03) : 865 - 872
  • [5] DROBYSKI WR, 1993, BLOOD, V82, P2310
  • [6] International uniform response criteria for multiple myeloma
    Durie, B. G. M.
    Harousseau, J-L
    Miguel, J. S.
    Blade, J.
    Barlogie, B.
    Anderson, K.
    Gertz, M.
    Dimopoulos, M.
    Westin, J.
    Sonneveld, P.
    Ludwig, H.
    Gahrton, G.
    Beksac, M.
    Crowley, J.
    Belch, A.
    Boccadaro, M.
    Turesson, I.
    Joshua, D.
    Vesole, D.
    Kyle, R.
    Alexanian, R.
    Tricot, G.
    Attal, M.
    Merlini, G.
    Powles, R.
    Richardson, P.
    Shimizu, K.
    Tosi, P.
    Morgan, G.
    Rajkumar, S. V.
    [J]. LEUKEMIA, 2006, 20 (09) : 1467 - 1473
  • [7] Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study
    Fielding, Adele K.
    Richards, Susan M.
    Chopra, Rajesh
    Lazarus, Hillard M.
    Litzow, Mark R.
    Buck, Georgina
    Durrant, I. Jill
    Luger, Selina M.
    Marks, David I.
    Franklin, Ian M.
    McMillan, Andrew K.
    Tallman, Martin S.
    Rowe, Jacob M.
    Goldstone, Anthony H.
    [J]. BLOOD, 2007, 109 (03) : 944 - 950
  • [8] Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: Harnessing graft-versus-leukemia without myeloablative therapy
    Giralt, S
    Estey, E
    Albitar, M
    vanBesien, K
    Rondon, G
    Anderlini, P
    OBrien, S
    Khouri, I
    Gajewski, J
    Mehra, R
    Claxton, D
    Andersson, B
    Beran, M
    Przepiorka, D
    Koller, C
    Kornblau, S
    Korbling, M
    Keating, M
    Kantarjian, H
    Champlin, R
    [J]. BLOOD, 1997, 89 (12) : 4531 - 4536
  • [9] Gurman G, 1996, BONE MARROW TRANSPL, V18, P825
  • [10] Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection
    Hale, G
    Zhang, MJ
    Bunjes, D
    Prentice, HG
    Spence, D
    Horowitz, MM
    Barrett, AJ
    Waldmann, H
    [J]. BLOOD, 1998, 92 (12) : 4581 - 4590