Genetically modified donor leukocyte transfusion and Graft-versus-Leukemia effect after allogeneic stem cell transplantation.
Posted by rob on November 26, 2010 under Uncategorized | 
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Genetically modified donor leukocyte transfusion and Graft-versus-Leukemia effect after allogeneic stem cell transplantation.
Hum Gene Ther. 2010 Nov 23;
Authors: Borchers S, Provasi E, Benati C, Dammann E, Radrizzani M, Krons A, Kuehnau W, Schmidke J, von Neuhoff N, Stadler M, Ciceri F, Bonini C, Ganser A, Hertenstein B, Mischak-Weissinger EM
Seven patients with acute myeloid leukemia (AML) and two patients with chronic myelogenous leukemia (CML) were transplanted from HLA-identical sibling donors with CD34+-enriched stem cells (HSCT) 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 the herpes simplex thymidine-kinase (HSV-Tk) and the truncated version of low affinity nerve growth factor receptor (?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 seven AML patients. No positivity for the aGVHD grade II specific proteomic pattern was observed. Only one patient developed aGvHD grade I. To date, 3 AML patients relapsed, one responded to the transfusion of 3 untransduced, escalating DLI from the original donor and is in complete remission. Two were re-transplanted with non-T-cell depleted peripheral blood stem cells from their original donors and died post re-transplantation from septic complications or relapse, respectively. In one CML-patient, loss of bcr-abl gene expression was observed following an expansion of transduced cells. Seven of nine patients are alive and in complete remission.
PMID: 21091264 [PubMed - as supplied by publisher]