Manuel Jurado1, Claudia De La Mata2, Antonio Ruiz-García3, Elisa López-Fernández2, Olga Espinosa3, María José Remigia4, Lucía Moratalla2, Rosa Goterris4, Paloma García-Martín2, Francisco Ruiz-Cabello5, Sebastián Garzón6, María Jesús Pascual7, Ildefonso Espigado8, Carlos Solano9. 1. Department of Hematology, Complejo Hospitalario Universitario, Granada, Spain; Genyo Pfizer, Universidad de Granada, Junta de Andalucía, Centre for Genomics and Oncological Research (GENYO), Granada, Spain. Electronic address: manuel.jurado.sspa@juntadeandalucia.es. 2. Department of Hematology, Complejo Hospitalario Universitario, Granada, Spain. 3. Cellular manufacturing Unit, Instituto de Investigación Biosanitaria (IBS), Complejo Hospitalario Universitario, Granada, Spain. 4. Department of Hematology, Hospital Clínico, Valencia, Spain. 5. Department of Immunology, Complejo Hospitalario Universitario, Granada, Spain. 6. Department of Hematology, Hospital General, Jerez, Spain. 7. Department of Hematology, Hospital Carlos Haya, Málaga, Spain. 8. Department of Hematology, Hospital Virgen del Rocío, Sevilla, Spain. 9. Department of Hematology, Hospital Clínico, Valencia, Spain; School of Medicine, University of Valencia, Spain.
Abstract
BACKGROUND AIMS: Despite the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the procedure is still associated with high toxicity in patients with refractory graft-versus-host disease (GvHD). Mesenchymal stromal cells (MSCs) are a new mode of therapy in the context of allo-HSCT. The objective of this study was to evaluate the safety and feasibility of the use of adipose tissue-derived MSCs (AT-MSCs) in patients with chronic GvHD. METHODS:Fourteen patients with moderate (n = 7) or severe (n = 7) chronic GvHD received 1 × 106/kg (group A, n = 9) or 3 × 106/kg (group B, n = 5) AT-MSCs with cyclosporine and prednisone as first-line therapy. RESULTS:Ten of the 14 patients were able to continue under the protocol: 80% were in complete remission, and 100% were off of steroids at week 56. The remaining 4 patients either worsened from chronic GvHD (n = 3) or abandoned the study (n = 1). At the end of the study, 11 of 14 patients are alive (overall survival 71.4%, median survival of 45.3 weeks). No suspected unexpected serious adverse reactions occurred during the trial. Neither relapse of underlying disease nor mortality due to infection was observed in this cohort. Biological studies showed increased CD19, CD4 and tumor necrosis factor-α with a temporary decrease in natural killer cells. DISCUSSION: AT-MSCs, in combination with immunosuppressive therapy, may be considered feasible and safe and likely would have an impact on the course of chronic GvHD. More studies are warranted to understand the potential benefits of AT-MSCs in these patients.
RCT Entities:
BACKGROUND AIMS: Despite the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the procedure is still associated with high toxicity in patients with refractory graft-versus-host disease (GvHD). Mesenchymal stromal cells (MSCs) are a new mode of therapy in the context of allo-HSCT. The objective of this study was to evaluate the safety and feasibility of the use of adipose tissue-derived MSCs (AT-MSCs) in patients with chronic GvHD. METHODS: Fourteen patients with moderate (n = 7) or severe (n = 7) chronic GvHD received 1 × 106/kg (group A, n = 9) or 3 × 106/kg (group B, n = 5) AT-MSCs with cyclosporine and prednisone as first-line therapy. RESULTS: Ten of the 14 patients were able to continue under the protocol: 80% were in complete remission, and 100% were off of steroids at week 56. The remaining 4 patients either worsened from chronic GvHD (n = 3) or abandoned the study (n = 1). At the end of the study, 11 of 14 patients are alive (overall survival 71.4%, median survival of 45.3 weeks). No suspected unexpected serious adverse reactions occurred during the trial. Neither relapse of underlying disease nor mortality due to infection was observed in this cohort. Biological studies showed increased CD19, CD4 and tumor necrosis factor-α with a temporary decrease in natural killer cells. DISCUSSION: AT-MSCs, in combination with immunosuppressive therapy, may be considered feasible and safe and likely would have an impact on the course of chronic GvHD. More studies are warranted to understand the potential benefits of AT-MSCs in these patients.
Authors: Dinh-Toi Chu; Tiep Tien Nguyen; Nguyen Le Bao Tien; Dang-Khoa Tran; Jee-Heon Jeong; Pham Gia Anh; Vo Van Thanh; Dang Tien Truong; Thien Chu Dinh Journal: Cells Date: 2020-02-28 Impact factor: 6.600
Authors: Christopher J Rogers; Robert J Harman; Bruce A Bunnell; Martin A Schreiber; Charlie Xiang; Fu-Sheng Wang; Antonio F Santidrian; Boris R Minev Journal: J Transl Med Date: 2020-05-18 Impact factor: 5.531
Authors: Tik Shing Cheung; Giuliana Minani Bertolino; Chiara Giacomini; Martin Bornhäuser; Francesco Dazzi; Antonio Galleu Journal: Front Immunol Date: 2020-06-25 Impact factor: 7.561