Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells.
Allogeneic stem cell transplantation (allo-HSCT) is one of the curative treatments for hematologic malignancies, but is hampered by severe complications, such as acute or chronic graft-versus-host-disease (aGvHD; cGvHD) and infections. CD34-selcetion of stem cells reduces the risk of aGvHD, but also...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00076/full |
| _version_ | 1818908523017273344 |
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| author | Eva Maria Weissinger Sylvia eBorchers Anna eSilvani Elena eProvasi Marina eRadrizzani Irene Katarina Beckmann Claudia eBenati Joerg eSchmidtke Wolfgang eKuehnau Patrick eSchweier Susanne eLuther Ivonne eFernadez-Munoz Gernot eBeutel Fabio eCiceri Chiara eBonini Arnold eGanser Bernd eHertenstein Michael eStadler |
| author_facet | Eva Maria Weissinger Sylvia eBorchers Anna eSilvani Elena eProvasi Marina eRadrizzani Irene Katarina Beckmann Claudia eBenati Joerg eSchmidtke Wolfgang eKuehnau Patrick eSchweier Susanne eLuther Ivonne eFernadez-Munoz Gernot eBeutel Fabio eCiceri Chiara eBonini Arnold eGanser Bernd eHertenstein Michael eStadler |
| author_sort | Eva Maria Weissinger |
| collection | DOAJ |
| description | Allogeneic stem cell transplantation (allo-HSCT) is one of the curative treatments for hematologic malignancies, but is hampered by severe complications, such as acute or chronic graft-versus-host-disease (aGvHD; cGvHD) and infections. CD34-selcetion of stem cells reduces the risk of aGvHD, but also leads to increased infectious complications and relapse. Thus, we studied the efficacy, safety and feasibility of transfer of gene modified donor T-cells shortly after allo-HSCT in two clinical trials between 2002 and 2007 and here we compare the results to unmodified donor leukocyte transfusion (DLI). The aim of these trials was to provide patients with the protection of T-cells after T-cell-depleted allo-HSCT in the matched or mismatched donor setting with an option to delete transduced T-cells, if severe aGvHD occurred within the trial period. Donor-T-cells were transduced with the replication-deficient retrovirus SFCMM-3, expressing HSV-Tk and the truncated LNGFR for selection of transduced cells. Transduced cells were transfused either after day +60 (matched donors) or on day +42 (haploidentical donors).Nine patients were included in the first trial (MHH; 2002 until 2007) 2 were included in TK007 (2005-2009) and 6 serve as a control group for outcome after haploidentical transplantation without HSV-TK-transduced DLI. Three patients developed acute GvHD, two had grade I of the skin, one had aGvHD on day +131 (post-HSCT; +89 post-HSV-Tk DLI) grade II, which was successfully controlled by ganciclovir (GCV). Donor chimerism was stabilized after transfusion of the transduced cells in all patients treated. Functionality of HSV-Tk gene expressing T-cells was shown by loss of bcr-abl gene expression as well as by control of cytomegalovirus-reactivation. To date, 6patients have relapsed and died, 2 after a second HSCT without T-cell depletion or administration of unmodified T-cells. Eleven patients (7 post-HSV-Tk DLI) are alive and well to date. |
| first_indexed | 2024-12-19T22:12:22Z |
| format | Article |
| id | doaj.art-15726f7eb9cc44d5aa393398c9ad1d05 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T22:12:22Z |
| publishDate | 2015-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-15726f7eb9cc44d5aa393398c9ad1d052022-12-21T20:03:52ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122015-04-01610.3389/fphar.2015.00076128703Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells.Eva Maria Weissinger0Sylvia eBorchers1Anna eSilvani2Elena eProvasi3Marina eRadrizzani4Irene Katarina Beckmann5Claudia eBenati6Joerg eSchmidtke7Wolfgang eKuehnau8Patrick eSchweier9Susanne eLuther10Ivonne eFernadez-Munoz11Gernot eBeutel12Fabio eCiceri13Chiara eBonini14Arnold eGanser15Bernd eHertenstein16Michael eStadler17Hannover Medical SchoolHannover Medical SchoolMolmedHospitale San RaffaeleMolmedHannover Medical SchoolMolmedHannover Medical SchoolHannover Medical SchoolHannover Medical SchoolHannover Medical SchoolHannover Medical SchoolHannover Medical SchoolHospitale San RaffaeleHospitale San RaffaeleHannover Medical SchoolKlinikum Bremen MitteKlinikum Bremen MitteAllogeneic stem cell transplantation (allo-HSCT) is one of the curative treatments for hematologic malignancies, but is hampered by severe complications, such as acute or chronic graft-versus-host-disease (aGvHD; cGvHD) and infections. CD34-selcetion of stem cells reduces the risk of aGvHD, but also leads to increased infectious complications and relapse. Thus, we studied the efficacy, safety and feasibility of transfer of gene modified donor T-cells shortly after allo-HSCT in two clinical trials between 2002 and 2007 and here we compare the results to unmodified donor leukocyte transfusion (DLI). The aim of these trials was to provide patients with the protection of T-cells after T-cell-depleted allo-HSCT in the matched or mismatched donor setting with an option to delete transduced T-cells, if severe aGvHD occurred within the trial period. Donor-T-cells were transduced with the replication-deficient retrovirus SFCMM-3, expressing HSV-Tk and the truncated LNGFR for selection of transduced cells. Transduced cells were transfused either after day +60 (matched donors) or on day +42 (haploidentical donors).Nine patients were included in the first trial (MHH; 2002 until 2007) 2 were included in TK007 (2005-2009) and 6 serve as a control group for outcome after haploidentical transplantation without HSV-TK-transduced DLI. Three patients developed acute GvHD, two had grade I of the skin, one had aGvHD on day +131 (post-HSCT; +89 post-HSV-Tk DLI) grade II, which was successfully controlled by ganciclovir (GCV). Donor chimerism was stabilized after transfusion of the transduced cells in all patients treated. Functionality of HSV-Tk gene expressing T-cells was shown by loss of bcr-abl gene expression as well as by control of cytomegalovirus-reactivation. To date, 6patients have relapsed and died, 2 after a second HSCT without T-cell depletion or administration of unmodified T-cells. Eleven patients (7 post-HSV-Tk DLI) are alive and well to date.http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00076/fullGene TherapyGene Transfer, HorizontalGraft vs Host Diseaseproteomics dataallogeneic stem cell transplantation |
| spellingShingle | Eva Maria Weissinger Sylvia eBorchers Anna eSilvani Elena eProvasi Marina eRadrizzani Irene Katarina Beckmann Claudia eBenati Joerg eSchmidtke Wolfgang eKuehnau Patrick eSchweier Susanne eLuther Ivonne eFernadez-Munoz Gernot eBeutel Fabio eCiceri Chiara eBonini Arnold eGanser Bernd eHertenstein Michael eStadler Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells. Frontiers in Pharmacology Gene Therapy Gene Transfer, Horizontal Graft vs Host Disease proteomics data allogeneic stem cell transplantation |
| title | Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells. |
| title_full | Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells. |
| title_fullStr | Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells. |
| title_full_unstemmed | Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells. |
| title_short | Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-Tk transduced T-cells. |
| title_sort | long term follow up of patients after allogeneic stem cell transplantation and transfusion of hsv tk transduced t cells |
| topic | Gene Therapy Gene Transfer, Horizontal Graft vs Host Disease proteomics data allogeneic stem cell transplantation |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00076/full |
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