Donor Lymphocyte Infusion for Relapsed Hematological Malignancies after Allogeneic Hematopoietic Cell Transplantation: Prognostic Relevance of the Initial CD3+ T Cell Dose

被引:70
作者
Bar, Merav [1 ,2 ]
Sandmaier, Brenda M. [1 ,2 ]
Inamoto, Yoshihiro [1 ]
Bruno, Benedetto [3 ]
Hari, Parameswaran [4 ]
Chauncey, Thomas [1 ,2 ,5 ]
Martin, Paul J. [1 ,2 ]
Storb, Rainer [1 ,2 ]
Maloney, David G. [1 ,2 ]
Storer, Barry [1 ,3 ,6 ]
Flowers, Mary E. D. [1 ,2 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA
[2] Univ Washington, Dept Med, Seattle, WA USA
[3] Univ Turin, Turin, Italy
[4] Med Coll Wisconsin, Milwaukee, WI 53226 USA
[5] VA Puget Sound Hlth Care Syst, Seattle, WA USA
[6] Univ Washington, Dept Biostat, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
Donor lymphocyte infusion (DLI); Hematopoietic cell transplantation (HCT); CD3(+) T cells; Graft-versus-host disease (GVHD); Adoptive immunotherapy for relapse after HCT; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; LEUKOCYTE INFUSIONS; ADOPTIVE IMMUNOTHERAPY; CHRONIC GRAFT; MULTIPLE-MYELOMA; WORKING PARTY; CHEMOTHERAPY;
D O I
10.1016/j.bbmt.2013.03.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The impact of donor lymphocyte infusion (DLI) initial cell dose on its outcome is known in patients with chronic myeloid leukemia but limited in patients with other hematological malignancies. In this retrospective study, we evaluated the effect of initial DLI CD3(+) cell dose on graft-versus-host disease (GVHD) and overall survival after DLI given for relapse of any hematological malignancies after allogeneic hematopoietic cell transplantation (HCT) with high- or reduced-intensity conditioning. The cohort included 225 patients. Initial DLI CD3(+) cell dose per kilogram of recipient body weight was <= 1 x 10(7) (n = 84; group A), >1.0 to <10 x 10(7) (n = 58; group B), and >= 10 x 10(7) (n = 66; group C). The initial cell dose was unknown for the remaining 17 patients. Cumulative incidence rates of GVHD at 12 months after DLI were 21%, 45%, and 55% for groups A, B, and C, respectively. Multivariate analysis showed that initial DLI CD3(+) cell >= 10 x 10(7) dose per kilogram is associated with an increased risk of GVHD after DLI (P = .03). Moreover, an initial DLI CD3(+) cell dose of 10 x 10(7) or higher did not decrease the risk of relapse and did not improve overall survival. Thus, these results support the use of less than 10 x 10(7) CD3(+) cell per kilogram as the initial cell dose of DLI for treatment of persistent or recurrent hematological malignancy after HCT. (C) 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:949 / 957
页数:9
相关论文
共 36 条
[1]   Toxicity and efficacy of defined doses of CD4+ donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant [J].
Alyea, EP ;
Soiffer, RJ ;
Canning, C ;
Neuberg, D ;
Schlossman, R ;
Pickett, C ;
Collins, H ;
Wang, YL ;
Anderson, KC ;
Ritz, J .
BLOOD, 1998, 91 (10) :3671-3680
[2]   The current status of hematopoietic cell transplantation [J].
Appelbaum, FR .
ANNUAL REVIEW OF MEDICINE-SELECTED TOPICS IN THE CLINICAL SCIENCES, 2003, 54 :491-512
[3]  
ATKINSON K, 1989, BONE MARROW TRANSPL, V4, P247
[4]   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
[5]   Molecules and mechanisms of the graft-versus-leukaemia effect [J].
Bleakley, M ;
Riddell, SR .
NATURE REVIEWS CANCER, 2004, 4 (05) :371-380
[6]   High response rate to donor lymphocyte infusion after allogeneic stem cell transplantation for indolent non-Hodgkin lymphoma [J].
Bloor, Adrian J. C. ;
Thomson, Kirsty ;
Chowdhry, Noha ;
Verfuerth, Stephane ;
Ings, Stuart J. ;
Chakraverty, Ranjon ;
Linch, David C. ;
Goldstone, Anthony H. ;
Peggs, Karl S. ;
Mackinnon, Stephen .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2008, 14 (01) :50-58
[7]   Outcome of patients developing GVHD after DLI given to treat CML relapse: a study by the chronic leukemia working party of the EBMT [J].
Chalandon, Y. ;
Passweg, J. R. ;
Schmid, C. ;
Olavarria, E. ;
Dazzi, F. ;
Simula, M. P. ;
Ljungman, P. ;
Schattenberg, A. ;
de Witte, T. ;
Lenhoff, S. ;
Jacobs, P. ;
Volin, L. ;
Iacobelli, S. ;
Finke, J. ;
Niederwieser, D. ;
Guglielmi, C. .
BONE MARROW TRANSPLANTATION, 2010, 45 (03) :558-564
[8]   Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse [J].
Choi, SJ ;
Lee, JH ;
Lee, JH ;
Kim, S ;
Seol, M ;
Lee, YS ;
Lee, JS ;
Kim, WK ;
Chi, HS ;
Lee, KH .
LEUKEMIA, 2004, 18 (11) :1789-1797
[9]   Donor leukocyte infusions in acute lymphocytic leukemia [J].
Collins, RH ;
Goldstein, S ;
Giralt, S ;
Levine, J ;
Porter, D ;
Drobyski, W ;
Barrett, J ;
Johnson, M ;
Kirk, A ;
Horowitz, M ;
Parker, P .
BONE MARROW TRANSPLANTATION, 2000, 26 (05) :511-516
[10]   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