Analysis of Cell Subsets in Donor Lymphocyte Infusions from HLA Identical Sibling Donors after Allogeneic Hematopoietic Cell Transplant

被引:3
作者
Orti, Guillermo [1 ,2 ]
Palacio-Garcia, Carles [2 ]
Garcia-Cadenas, Irene [3 ,4 ]
Sanchez-Ortega, Isabel [5 ]
Jose Jimenez, Maria [6 ]
Azqueta, Carmen [7 ]
Villacampa, Guillermo [8 ]
Ferra, Christelle [6 ]
Parody, Rocio [5 ]
Martino, Rodrigo [3 ,4 ]
Bosch, Francesc [2 ]
Querol, Sergi [7 ]
Valcarcel, David [2 ]
机构
[1] Univ Autonoma Barcelona, Dept Med, Barcelona, Spain
[2] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol VHIO, Dept Hematol, Barcelona, Spain
[3] Univ Autonoma Barcelona, Hematol Dept, Hosp Santa Creu & St Pau, Jose Carreras Leukemia Res Inst, Barcelona, Spain
[4] Univ Autonoma Barcelona, IIB St Pau, Barcelona, Spain
[5] Hosp Duran & Reynals, Inst Catala Oncol, Hematol Dept, Barcelona, Spain
[6] Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Jose Carreras Res Inst, Hematol Dept, Barcelona, Spain
[7] Banc Sang & Teixits, Cellular Therapy Unit, Barcelona, Spain
[8] Vall dHebron Inst Oncol, Oncol Data Sci ODysSey Grp, Barcelona, Spain
来源
TRANSPLANTATION AND CELLULAR THERAPY | 2021年 / 27卷 / 01期
关键词
Donor lymphocyte infusion; Allogeneic hematopoietic cell transplant; Graft-versus-host disease; Naive T cell; CD27(+) B cell; Mononuclear cells; VERSUS-HOST-DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; MEMORY T-CELLS; WORKING GROUP; MARROW-TRANSPLANTATION; LEUKOCYTE INFUSIONS; PHASE-I; GRAFT; RELAPSE;
D O I
10.1016/j.bbmt.2020.09.024
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Donor lymphocytes infusions (DLIs) are amajor therapeutic approach to treat relapse and mixed chimerism after allogeneic hematopoietic cell transplant (alloHCT). The impact of the composition regarding different cell subsets in the development of graft-versus-host disease (GVHD) is not fully understood. We performed a cell subsets analysis of 56 DLIs from fully HLA-compatible identical matched sibling donors (MSDs) in 36 alloHCT patients and studied its association with GVHD. A median of one DLIwas infused per patient. Fourteen patients (38%) developed GVHD. The cell composition analysis of the first DLI (DLI1) showed that a high dose of B cells (P =.03) and CD27(+) B cells (P <.01) was associated with GVHD. We identified DLI dose cutoff points for several cell populations above which GVHD was more frequent (CD8(+) T-N >3 x 10(6) cells/kg, CD27(+) B cells >2.6 x 10(6)/kg, CD27(+) NK >0.35 x 10(6) cells/kg, and mononuclear cells >0.83 x 10(8)/kg). Noteworthy, the proportion of CD4(+) naive T cells (T-N) or unselected T-N was not linked with GVHD and a DLI1 containing a higher dose of regulatory T cells was not protective for GVHD. We studied several transplant clinical variables and did not find any association with GVHD. Altogether, this study provides a comprehensive analysis of the cell populations in a DLI fromMSDs and identifies potential key cell subsets, which provides insight for the understanding of GVHD after DLI. (C) 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:53.e1 / 53.e8
页数:8
相关论文
共 42 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]   Phenotype and Function of Human T Lymphocyte Subsets: Consensus and Issues [J].
Appay, Victor ;
van Lier, Rene A. W. ;
Sallusto, Federica ;
Roederer, Mario .
CYTOMETRY PART A, 2008, 73A (11) :975-983
[3]  
ATKINSON K, 1990, BONE MARROW TRANSPL, V5, P69
[4]   CD4+CD25high regulatory cells in human peripheral blood [J].
Baecher-Allan, C ;
Brown, JA ;
Freeman, GJ ;
Hafler, DA .
JOURNAL OF IMMUNOLOGY, 2001, 167 (03) :1245-1253
[5]   Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts [J].
Bleakley, Marie ;
Heimfeld, Shelly ;
Loeb, Keith R. ;
Jones, Lori A. ;
Chaney, Colette ;
Seropian, Stuart ;
Cooley, Ted A. ;
Sommermeyer, Franziska ;
Riddell, Stanley R. ;
Shlomchik, Warren D. .
JOURNAL OF CLINICAL INVESTIGATION, 2015, 125 (07) :2677-2689
[6]  
CHAMPLIN R, 1990, BLOOD, V76, P418
[7]   Naive subset develops the most important alloreactive response among human CD4+ T lymphocytes in Human Leukocyte Antigen-identical related setting [J].
Cherel, Mathilde ;
Choufi, Bachra ;
Trauet, Jacques ;
Cracco, Pascale ;
Dessaint, Jean-Paul ;
Yakoub-Agha, Ibrahim ;
Labalette, Myriam .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2014, 92 (06) :491-496
[8]  
Cheson BD, 2000, BLOOD, V96, P3671
[9]   Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification [J].
Cheson, Bruce D. ;
Fisher, Richard I. ;
Barrington, Sally F. ;
Cavalli, Franco ;
Schwartz, Lawrence H. ;
Zucca, Emanuele ;
Lister, T. Andrew .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :3059-+
[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