Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation
Martino Introna, Federico Lussana, Alessandra Algarotti, Elisa Gotti, Rut Valgardsdottir, Caterina Micò, Anna Grassi, Chiara Pavoni, Maria Luisa Ferrari, Federica Delaini, Elisabetta Todisco, Irene Cavattoni, Sara Deola, Ettore Biagi, Adriana Balduzzi, Attilio Rovelli, Matteo Parma, Sara Napolitano, Giusy Sgroi, Emanuela Marrocco, Paolo Perseghin, Daniela Belotti, Benedetta Cabiati, Giuseppe Gaipa, Josée Golay, Andrea Biondi, Alessandro Rambaldi, Martino Introna, Federico Lussana, Alessandra Algarotti, Elisa Gotti, Rut Valgardsdottir, Caterina Micò, Anna Grassi, Chiara Pavoni, Maria Luisa Ferrari, Federica Delaini, Elisabetta Todisco, Irene Cavattoni, Sara Deola, Ettore Biagi, Adriana Balduzzi, Attilio Rovelli, Matteo Parma, Sara Napolitano, Giusy Sgroi, Emanuela Marrocco, Paolo Perseghin, Daniela Belotti, Benedetta Cabiati, Giuseppe Gaipa, Josée Golay, Andrea Biondi, Alessandro Rambaldi
Abstract
Seventy-four patients who relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocyte infusion (DLI) followed by cytokine-induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least 1 infusion of CIK cells was given to 59 patients, whereas 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute graft-versus-host disease (aGVHD) of grades I to II in 7 cases and grades III to IV in 5). In 8 of 12 cases, aGVHD developed during DLI treatment, leading to interruption of the cellular program in 3 patients, whereas in the remaining 5 cases aGVHD was controlled by steroids treatment, thus allowing the subsequent planned administration of CIK cells. Chronic GVHD (cGVHD) was observed in 11 patients (15%). A complete response was observed in 19 (26%), partial response in 3 (4%), stable disease in 8 (11%), early death in 2 (3%), and disease progression in 41 (56%). At 1 and 3 years, rates of progression-free survival were 31% and 29%, whereas rates of overall survival were 51% and 40%, respectively. By multivariate analysis, the type of relapse, the presence of cGVHD, and a short (<6 months) time from allogeneic hematopoietic stem cell transplantation to relapse were the significant predictors of survival. In conclusion, a low incidence of GVHD is observed after the sequential administration of DLI and CIK cells, and disease control can be achieved mostly after a cytogenetic or molecular relapse.
Keywords: Cytokine-induced killer (CIK) cells; DLI; Passive immunotherapy; Relapse after allo-BMT.
Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Source: PubMed