title: Donor CD3(+) lymphocyte infusion after reduced intensity conditioning allogeneic stem cell transplantation: single-center experience.
abstract: Donor lymphocyte infusions (DLI) can induce remission in patients with hematologic malignancies who relapse after allogeneic stem cell transplantation. However, graft-vs-host disease (GVHD) remains a major complication of this strategy. We have used escalating doses of DLI for many years, and wanted to assess the risk factors for GVHD and transplant-related mortality as well as disease outcomes according to the reason for DLI. We analyzed 65 patients who received a total of 111 DLI for different reasons and at different intervals after transplantation. Median number of DLI was 2 (range, 1-4), median interval between transplantation and DLI was 9 months (range, 1-41 months) and median number of infused CD3(+) cells/kg recipient body weight was 2.5 × 10(7) (range, 1 × 10(6)-11.8 × 10(7)). Reasons for DLI were relapse or progression in 37 patients (57%), residual disease in 15 patients (23%), and persistence of mixed chimerism in 13 patients (20%). Seven patients (11%) developed acute GVHD grade II to IV and 5 patients (8%) developed extensive chronic GVHD. In univariate analysis, we could identify a transplantation-DLI interval ≤6 months, the dose of DLI (≥1 × 10(7)), and DLI number as predictive factors of GVHD. In multivariate analysis, these results were confirmed only for the transplantation-DLI interval (hazard ratio = 19.48; 2.23-170.34; p = 0.007). Our findings indicate that this form of adoptive immunotherapy is well tolerated and induces a low incidence of GVHD and transplant-related mortality, supporting further investigation as an upfront modality to enhance the graft-vs-tumor response in high-risk patients.
authors.affiliation: Unité de Transplantation et de Thérapie Cellulaire, Institut Paoli-Calmettes, Marseille, France. elcheikhj@ipc.unicancer.fr
authors.forename: Jean
authors.initials: J
authors.lastname: El-Cheikh
authors.forename: Roberto
authors.initials: R
authors.lastname: Crocchiolo
authors.forename: Sabine
authors.initials: S
authors.lastname: Furst
authors.forename: Patrick
authors.initials: P
authors.lastname: Ladaique
authors.forename: Luca
authors.initials: L
authors.lastname: Castagna
authors.forename: Catherine
authors.initials: C
authors.lastname: Faucher
authors.forename: Boris
authors.initials: B
authors.lastname: Calmels
authors.forename: Claire
authors.initials: C
authors.lastname: Oudin
authors.forename: Claude
authors.initials: C
authors.lastname: Lemarie
authors.forename: Angela
authors.initials: A
authors.lastname: Granata
authors.forename: Raynier
authors.initials: R
authors.lastname: Devillier
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Reda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000032:analysis; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D017252:CD3 Complex