Laura Alonso1, Ana Méndez-Echevarría2,3, Francesc Rudilla4, Yasmina Mozo5,6, Pere Soler-Palacin7,8, Luisa Sisinni5,6, David Bueno5,6, Jacques Riviere7,8, Raquel de Paz9, Elena Sánchez-Zapardiel10,11, Sergi Querol12, Rebeca Rodriguez-Pena10,11, Eduardo López-Granados10,11, Ramón Gimeno13, Cristina Díaz de Heredia1, Antonio Pérez-Martínez5,6. 1. HSCT Department, Hospital Vall d'Hebron, Barcelona, Spain. 2. Paediatric Infectious Diseases Department, La Paz University Hospital, Madrid, Spain. amendezes@yahoo.es. 3. Translational Research Network in Pediatric Infectious Diseases (RITIP), Paseo de la Castellana 261, 28046, Madrid, Spain. amendezes@yahoo.es. 4. Immunogenetics and Histocompatibility Laboratory, Banc de Sang i Teixits, Barcelona, Spain. 5. Paediatric Hemato-Oncology Department, La Paz University Hospital, Madrid, Spain. 6. Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, La Paz Institute for Health Research (IdiPAZ), Madrid, Spain. 7. Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d'Hebron Research Institute, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. 8. Jeffrey Model Foundation Excellence Center, Barcelona, Spain. 9. Hematology Department, La Paz University Hospital, Madrid, Spain. 10. Immunology Department, La Paz University Hospital, Madrid, Spain. 11. IdiPAZ Institute for Health Research, Madrid, Spain. 12. Cellular Therapy Unit, Cord Blood Bank, Centre Frederic Duran i Jordà, Barcelona, Spain. 13. Laboratory of Immunology, Department of Pathology, Hospital del Mar, Barcelona, Spain.
Abstract
PURPOSE: Use of adoptive immunotherapy with virus-specific T cells (VST) in patients with inborn errors of immunity prior to hematopoietic stem cell transplantation (HSCT) has been reported in few patients. We report our experience, reviewing all the cases previously reported. METHODS: We report four children with inborn errors of immunity who received VST infusion in a pre-HSCT setting in two reference centers in Spain and review all inborn errors of immunity cases previously reported. RESULTS: Taking into account our four cases, nine children have been reported to receive VST prior to HSCT to date: 3 severe combined immunodeficiency, 2 CTPS1 deficiency, 1 dyskeratosis congenital, 1 ORAI1 deficiency, 1 Rothmund-Thomson syndrome, and 1 combined immunodeficiency without confirmed genetic defect. In four patients, immunotherapy resulted in clinical improvement, allowing to proceed to HSCT. In these cases, the infusion was started closely to viral diagnosis [mean time 28 days (IQR; 17-52 days)], and the VST was followed shortly thereafter by HSCT [mean time 28 days (IQR; 10-99 days)]. Viremia was controlled after HSCT in two cases (performed 7 and 36 days after the infusion). Multiple infusions were required in many cases. Five out of nine patients died before receiving HSCT. These patients presented with a prolonged and uncontrolled infection before VST administration [mean time from viral diagnosis to VST infusion was 176 days (IQR; 54-1687)]. CONCLUSIONS: In patients with inborn errors of immunity, the efficacy of VST for treating disseminated viral infections in pre-transplant settings seems to have a limited efficacy. However, this therapy could be used in a pre-emptive setting before severe viral disease occurs or closely to HSCT.
PURPOSE: Use of adoptive immunotherapy with virus-specific T cells (VST) in patients with inborn errors of immunity prior to hematopoietic stem cell transplantation (HSCT) has been reported in few patients. We report our experience, reviewing all the cases previously reported. METHODS: We report four children with inborn errors of immunity who received VST infusion in a pre-HSCT setting in two reference centers in Spain and review all inborn errors of immunity cases previously reported. RESULTS: Taking into account our four cases, nine children have been reported to receive VST prior to HSCT to date: 3 severe combined immunodeficiency, 2 CTPS1 deficiency, 1 dyskeratosis congenital, 1 ORAI1 deficiency, 1 Rothmund-Thomson syndrome, and 1 combined immunodeficiency without confirmed genetic defect. In four patients, immunotherapy resulted in clinical improvement, allowing to proceed to HSCT. In these cases, the infusion was started closely to viral diagnosis [mean time 28 days (IQR; 17-52 days)], and the VST was followed shortly thereafter by HSCT [mean time 28 days (IQR; 10-99 days)]. Viremia was controlled after HSCT in two cases (performed 7 and 36 days after the infusion). Multiple infusions were required in many cases. Five out of nine patients died before receiving HSCT. These patients presented with a prolonged and uncontrolled infection before VST administration [mean time from viral diagnosis to VST infusion was 176 days (IQR; 54-1687)]. CONCLUSIONS: In patients with inborn errors of immunity, the efficacy of VST for treating disseminated viral infections in pre-transplant settings seems to have a limited efficacy. However, this therapy could be used in a pre-emptive setting before severe viral disease occurs or closely to HSCT.
Entities:
Keywords:
Inborn errors of immunity; immunotherapy; primary immunodeficiency diseases; viruses
Authors: Holly K Miller; Patrick J Hanley; Haili Lang; Christopher A Lazarski; Elizabeth A Chorvinsky; Sarah McCormack; Lauren Roesch; Shuroug Albihani; Marcus Dean; Fahmida Hoq; Roberta H Adams; Catherine M Bollard; Michael D Keller Journal: Biol Blood Marrow Transplant Date: 2018-05-09 Impact factor: 5.742
Authors: Stuart G Tangye; Waleed Al-Herz; Aziz Bousfiha; Talal Chatila; Charlotte Cunningham-Rundles; Amos Etzioni; Jose Luis Franco; Steven M Holland; Christoph Klein; Tomohiro Morio; Hans D Ochs; Eric Oksenhendler; Capucine Picard; Jennifer Puck; Troy R Torgerson; Jean-Laurent Casanova; Kathleen E Sullivan Journal: J Clin Immunol Date: 2020-01-17 Impact factor: 8.317