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Rapid immune recovery and graft-versus-host disease-like engraftment syndrome following adoptive transfer of Costimulated autologous T cells
- Source :
- Clinical cancer research : an official journal of the American Association for Cancer Research. 15(13)
- Publication Year :
- 2009
-
Abstract
- Purpose: Previously, we showed that adoptive transfer of in vivo vaccine-primed and ex vivo (anti-CD3/anti-CD28) costimulated autologous T cells (ex-T) at day +12 after transplant increased CD4 and CD8 T-cell counts at day +42 and augmented vaccine-specific immune responses in patients with myeloma. Here, we investigated the safety and kinetics of T-cell recovery after infusing ex-T at day +2 after transplant.Experimental Design: In this phase I/II two-arm clinical trial, 50 patients with myeloma received autografts after high-dose melphalan followed by infusions of ex-T at day +2 after transplant. Patients also received pretransplant and posttransplant immunizations using a pneumococcal conjugate vaccine only (arm B; n = 24) or the pneumococcal conjugate vaccine plus an HLA-A2–restricted multipeptide vaccine for HLA-A2+ patients (arm A; n = 26).Results: The mean number of T cells infused was 4.26 × 1010 (range, 1.59-5.0). At day 14 after transplant, the median CD3, CD4, and CD8 counts were 4,198, 1,545, and 2,858 cells/μL, respectively. Interleukin (IL)-6 and IL-15 levels increased early after transplant and IL-15 levels correlated significantly to day 14 T-cell counts. Robust vaccine-specific B- and T-cell responses were generated. T-cell infusions were well tolerated with no effect on hematopoietic recovery. Eight patients (16%) developed a T-cell “engraftment syndrome” characterized by diarrhea and fever that was clinically and histopathologically indistinguishable from grade 1 to 3 acute graft-versus-host disease (GVHD) of the gastrointestinal tract (seven patients) and/or grade 1 to 2 cutaneous GVHD (four patients).Conclusions: Adoptive T-cell transfers achieve robust T-cell recovery early after transplant and induce moderate-to-severe autologous GVHD in a subset of patients.
- Subjects :
- Melphalan
Adult
Male
Cancer Research
Adoptive cell transfer
medicine.medical_treatment
T-Lymphocytes
Graft vs Host Disease
Engraftment Syndrome
Lymphocyte Activation
Immunotherapy, Adoptive
Transplantation, Autologous
Pneumococcal conjugate vaccine
Article
Immune system
HLA-A2 Antigen
Medicine
Humans
Cells, Cultured
Aged
business.industry
Immunotherapy
Recovery of Function
Syndrome
Middle Aged
Myeloablative Agonists
medicine.disease
Transplantation
Graft-versus-host disease
Oncology
Immunology
Female
business
Multiple Myeloma
Algorithms
medicine.drug
Subjects
Details
- ISSN :
- 15573265
- Volume :
- 15
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Accession number :
- edsair.doi.dedup.....3b058f42bdbb4648b18c1d21c5006437