PubMed · 12146097
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L Muylle. 2002. What do we know?. https://pubmed.ncbi.nlm.nih.gov/12146097/
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Hematologic stem cell rescue after high-dose cytotoxic therapy is extensively used for the treatment of many hematopoietic and solid cancers. Gene marking studies suggest that occult tumor cells within the autograft may contribute to clinical relapse. To date purging of autografts contaminated with cancer cells has been unsuccessful. The selective oncolytic property of reovirus against myriad malignant histologies in in vitro, in vivo, and ex vivo systems has been previously demonstrated. In the present study we have shown that reovirus can successfully purge cancer cells within autografts. Human monocytic and myeloma cell lines as well as enriched ex vivo lymphoma, myeloma, and Waldenström macroglobulinemia patient tumor specimens were used in an experimental purging model. Viability of the cell lines or purified ex vivo tumor cells of diffuse large B-cell lymphoma, chronic lymphocytic leukemia, Waldenström macroglobulinemia, and small lymphocytic lymphoma was significantly reduced after reovirus treatment. Further, [35S]-methionine labeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of cellular proteins demonstrated reovirus protein synthesis and disruption of host cell protein synthesis as early as 24 hours. Admixtures of apheresis product with the abovementioned tumor cells and cell lines treated with reovirus showed complete purging of disease. In contrast, reovirus purging of enriched ex vivo multiple myeloma, Burkitt lymphoma, and follicular lymphoma was incomplete. The oncolytic action of reovirus did not affect CD34+ stem cells or their long-term colony-forming assays even after granulocyte colony-stimulating factor (G-CSF) stimulation. Our results indicate the ex vivo use of an unattenuated oncolytic virus as an attractive purging strategy for autologous stem cell transplantations.
Although worldwide experience with extracorporeal photochemotherapy (ECP) for GvHD treatment has grown enormously over the past decade, only a few pediatric centers have experience with ECP. Studies reporting clinical outcome in children with GvHD treated by ECP comprises a very limited number of patients with only few information described. This review article remain focused on the efficacy and the safety aspect of ECP in pediatric patients to provide information about the steps that should be taken to overcome the difficulties with ECP use in children with GvHD. Data concerning 19 children with acute GvHD and 54 children with chronic GvHD treated with ECP and reported so far have been considered. The principal reasons for the restriction in the use of ECP in children such as: (1) technical difficulties of leukapheresis procedures (venous access, hemodynamic, metabolic and hematological tolerance); and (2) the necessity of a specially adapted pediatric patient approach to improve the psychological tolerance of this treatment are discussed. The data of this retrospective review demonstrate that ECP is beneficial and well tolerated in children with GvHD. It can be safely used even in young children with low body weight and a poor performance status when it was performed by a qualified pediatric team. The observations concerning the response rate and onset suggest that in children with acute GvHD, ECP should be started early in the course of disease and employed over a relatively short period of time. As far as chronic GvHD is concerned, despite the fact that it is preferable to begin ECP early as second line therapy, it may also be beneficial in patients with late-stage disease.