Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation
- 15 September 2003
- journal article
- clinical trial
- Published by American Society of Hematology in Blood
- Vol. 102 (6), 2004-2013
- https://doi.org/10.1182/blood-2003-01-0095
Abstract
We explored the feasibility and toxicity of administering escalating doses of anti-CD3/CD28 ex vivo costimulated T cells as a therapeutic adjunct for patients with relapsed, refractory, or chemotherapy-resistant, aggressive non-Hodgkin lymphoma (NHL) following high-dose chemotherapy and CD34+-selected hematopoietic cell transplantation (HCT). Sixteen patients had infusions on day 14 after HCT of autologous T cells that had been stimulated using beads coated with anti-CD3 and anti-CD28 monoclonal antibodies. At baseline, the subjects had severe quantitative and functional T-cell impairments. The culture procedure partially reversed impaired cytokine responsiveness in T cells in vitro and in vivo. Transient dose-dependent infusion toxicities were observed. There was a rapid reconstitution of lymphocytes; however, there were persistent defects in CD4 T cells. Most interestingly, 5 patients had a delayed lymphocytosis between day 30 and day 120 after HCT. Maximal clinical responses included 5 patients with a complete response (CR), 7 patients with a partial response (PR), and 4 patients with stable disease. At a median follow-up of 33 months (range, 26-60 months), 5 patients are alive with stable or relapsed disease and 3 patients remain in CR. In conclusion, this phase 1 trial demonstrates that adoptive transfer of autologous costimulated T cells (1) is feasible in heavily pretreated patients with advanced NHL, (2) is associated with a rapid recovery of lymphocyte counts, (3) reverses cytokine activation deficits in vitro, and (4) is associated with delayed lymphocytosis in a subset of patients.This publication has 53 references indexed in Scilit:
- Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor LymphocytesScience, 2002
- CD34+-enriched–CD19+-depleted autologous peripheral blood stem cell transplantation for chronic lymphoproliferative disorders: High purging efficiency but increased risk of severe infectionsExperimental Hematology, 2002
- Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemiaLeukemia, 2002
- Immune reconstitution after autologous peripheral blood progenitor cell transplantation: Effect of interleukin-15 on T-cell survival and effector functionsExperimental Hematology, 2001
- Poor lymphocyte recovery following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphomaBritish Journal of Haematology, 1999
- Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignanciesBone Marrow Transplantation, 1998
- Influence of Interleukin-2 Regimens on Circulating Populations of Lymphocytes After Adoptive Transfer of Anti-CD3-Stimulated T CellsJournal of Immunotherapy, 1996
- Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin's LymphomaThe New England Journal of Medicine, 1995
- Multiple defects of T helper cell function in newly diagnosed patients with Hodgkin's diseaseEuropean Journal of Cancer, 1994
- Identification of the major late human cytomegalovirus matrix protein pp65 as a target antigen for CD8+ virus‐specific cytotoxic T lymphocytesJournal of Medical Virology, 1994