Subject(s)
Calreticulin/genetics , Hematopoietic Stem Cell Transplantation , Polymerase Chain Reaction , Primary Myelofibrosis/genetics , Alleles , Calreticulin/metabolism , Humans , Immunotherapy/methods , Janus Kinase 2/genetics , Janus Kinase 2/metabolism , Mutation , Primary Myelofibrosis/diagnosis , Primary Myelofibrosis/metabolism , Recurrence , Remission Induction , Time FactorsSubject(s)
Antigens, CD34/blood , Primary Myelofibrosis/blood , Primary Myelofibrosis/diagnosis , Primary Myelofibrosis/therapy , Stem Cell Transplantation , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Primary Myelofibrosis/genetics , Prognosis , Retrospective Studies , Transplantation, HomologousABSTRACT
In this retrospective study, we evaluated donor lymphocyte infusions given for relapsed (n=48) or persistent (n=15) myeloma following non-myeloablative allogeneic stem cell transplantation (Allo-SCT). Twenty-four of 63 patients (38.1%) responded: 12 patients (19.0%) with a partial response (PR) and 12 patients (19.0%) with a complete response (CR). Overall survival after donor lymphocyte infusions (DLI) was 23.6 months (1.0-50.7+). Median overall survival for non-responding patients was 23.6 months and has not been reached for the patients responding to DLI. In responders, progression-free survival after DLI was 27.8 months (1.2-46.2+). Patients with a PR had a median progression-free survival of 7.0 months, whereas patients with a CR to DLI had a median progression-free survival of 27.8 months. Major toxicities were acute graft-versus-host disease (GVHD) (38.1%) and chronic GVHD (42.9%). Seven patients (11.1%) died from treatment-related mortality. The only significant prognostic factors for response to DLI were the occurrence of acute and chronic GVHD. There was a trend towards significance for time between transplantation and DLI, and response. Donor lymphocyte infusion following non-myeloablative Allo-SCT is a valuable strategy for relapsed or persistent disease.
Subject(s)
Lymphocyte Transfusion , Multiple Myeloma/therapy , Stem Cell Transplantation , Acute Disease , Adult , Aged , Chronic Disease , Disease-Free Survival , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Humans , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/mortality , Recurrence , Remission Induction , Stem Cell Transplantation/mortality , Transplantation, Homologous , Treatment OutcomeABSTRACT
Peripheral T lymphocytes are a target of choice for many gene therapeutic strategies. Retrovirus-mediated transduction allows genomic integration and long-term expression of transgenes in target cells. Over many years, low transduction efficiency into primary T lymphocytes has limited clinical application of existing protocols. Recently, gene transfer rates > 50% have been achieved facilitating clinical studies. More attention is thus being focused on the ability of gene-modified cells to carry out innate as well as conferred functions in vivo and the influence of culture conditions, retroviral vector and host response thereon.
Subject(s)
Gene Transfer Techniques , Genetic Vectors , Retroviridae/genetics , T-Lymphocytes/physiology , Transduction, Genetic , Animals , Humans , Moloney murine leukemia virus/geneticsABSTRACT
Transplantation of suicide gene modified allogeneic T lymphocytes is an approach to prevent T cell mediated GVHD while preserving the 'graft-versus-leukemia' (GVL) effect of an allograft. A prerequisite for such a therapy is the efficient transduction of T cells with suitable vectors. Since existing techniques allow only insufficient transduction of T cells, the development of more efficient gene transfer protocols into these cells is of great importance. We present here a protocol for the highly efficient transduction of human primary T cells at high densities (1 x 10(6) cells/ml) by retroviral infection. The presented protocol allowed us to obtain transduction rates of more than 70% of CD3+ cells after two cycles of infection. It is based on the use of FBS-free media for both the production of retrovirus-containing supernatant, as well as the cultivation of the primary T cells. Since the protocol presented here works just as efficiently under large scale conditions, it may easily be adapted to clinical needs and 'good manufacturing practice' (GMP) standards.