Genetically modified donor leukocyte transfusion and graft-versus-leukemia effect after allogeneic stem cell transplantation
| Autor: | Sylvia Borchers, Julia Kontsendorn, Bernd Hertenstein, Michael Stadler, Elena Provasi, Wolfgang Kuehnau, Chiara Bonini, Nils von Neuhoff, Joerg Schmidtke, Eva M. Weissinger, Annika Krons, Arnold Ganser, Marina Radrizzani, Fabio Ciceri, Anna Silvani, Claudia Benati, Elke Dammann |
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| Přispěvatelé: | Borchers, S, Provasi, E, Silvani, A, Radrizzani, M, Benati, C, Dammann, E, Krons, A, Kontsendorn, J, Schmidtke, J, Kuehnau, W, von Neuhoff, N, Stadler, M, Ciceri, Fabio, Bonini, C, Ganser, A, Hertenstein, B, Weissinger, Em |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Proteomics Graft-vs-Leukemia Effect medicine.medical_treatment Receptors Antigen T-Cell alpha-beta Genetic Vectors CD34 Fusion Proteins bcr-abl Graft vs Host Disease Graft vs Leukemia Effect Hematopoietic stem cell transplantation Biology Chimerism Thymidine Kinase Transduction Genetic hemic and lymphatic diseases Leukemia Myelogenous Chronic BCR-ABL Positive Genetics medicine Humans Transgenes Molecular Biology Research Articles Immunosuppression Therapy Remission Induction Hematopoietic Stem Cell Transplantation Myeloid leukemia Immunosuppression Middle Aged medicine.disease Tissue Donors Transplantation Leukemia Myeloid Acute Leukocyte Transfusion surgical procedures operative Retroviridae Immunology Molecular Medicine Female Stem cell Chronic myelogenous leukemia |
| Zdroj: | Human gene therapy. 22(7) |
| ISSN: | 1557-7422 |
| Popis: | Seven patients with acute myeloid leukemia (AML) and two patients with chronic myelogenous leukemia (CML) were transplanted from HLA-identical sibling donors with CD34(+) cell-enriched stem cells (HSCTs) without further immunosuppression. The myeloablative standard transplantation protocol was adapted to include transfusion of gene-modified donor T cells after HSCT. Donor T cells were transduced with the replication-deficient retrovirus SFCMM-3, which expresses herpes simplex thymidine kinase (HSV-Tk) and a truncated version of low-affinity nerve growth factor receptor (Delta LNGFR) for selection and characterization of transduced cells. Transduced T cells were detectable in all patients during follow-up for up to 5 years after transfusion. Proteomic screening for development of acute graft-versus-host disease (aGvHD) was applied to five of the seven patients with AML. No positivity for the aGvHD grade II-specific proteomic pattern was observed. Only one patient developed aGvHD grade I. To date, three of the patients with AML relapsed; one responded to three escalating transfusions of lymphocytes from the original donor and is in complete remission. Two were retransplanted with non-T cell-depleted peripheral blood stem cells from their original donors and died after retransplantation of septic complications or relapse, respectively. In one patient with CML, loss of bcr-abl gene expression was observed after an expansion of transduced cells. Seven of nine patients are alive and in complete remission. |
| Databáze: | OpenAIRE |
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