A current definition of gene therapy is the infusion of a therapeutic gene, or cells transduced with the gene, in order to cure or prevent illnesses. This method can be used to add a functional gene into genomes containing a mutated version, which is left unmodified. However, gene therapy cannot be used to treat diseases caused by gain-of-function mutations, and leukemogenesis is often induced by integration of the vector into sites adjacent to proto-oncogenes. On the other hand, gene editing technologies, such as the CRISPR/Cas system, have been developed at a rapid pace and introduced into the field of gene therapy. This article describes the safety, efficacy, and ethics of gene therapy, by focusing on problems inherent to current gene therapy techniques involving gene addition, and the development of future gene therapies using gene correction.
The most significant obstacle hindering the improvement of transplant outcomes is death by transplant-related complications such as graft-versus-host disease, infection, or organ dysfunction. Severe veno-occlusive diseases or thrombotic microangiopathy in particular are causes of high mortality, and endothelial damage by thrombosis is a common cause of these complications. To reduce organ dysfunction, we administered danaparoid, an anticoagulant with high antiⅩa/antiⅡa activity, and found that transplant-related mortality was significantly decreased. As for late effects after transplantation, sterility was attenuated by elimination or reduction of busulfan, or total body irradiation. Overall, in order to reduce transplant-related early or late complications, it is important to improve supportive therapy or reduce the intensity of the conditioning regimen without increasing the relapse rate in malignant disorders.
We analyzed the relationship between unrelated donor characteristics (age, sex, height, body weight, and complete blood count) and nucleated cell count concentration in harvested bone marrow between August 2007 and November 2015 at our hospital. All 57 donors met the bone marrow harvesting criteria of Japan Marrow Donor Program. A stepwise multiple regression analysis indicated a significant correlation between the platelet count and the concentration of nucleated cells. Using the derived predictive formula, we illustrated bone marrow volume depending on the platelet count to obtain 2.3×108 nucleated cell count per patient’s body weight. In bone marrow transplantation for patients weighing<60 kg, it is possible to obtain adequate nucleated cell count by increasing their self-blood, even if their platelet counts are relatively low. In contrast, the maximum volume of self-blood may not make it possible to achieve required nucleated cell count for the patients weighing>70 kg. It may be a useful strategy that we select donors with high level of platelet count or who can provide their peripheral blood stem cell.
Chronic graft-versus-host disease (GVHD) occurs in approximately 30-50% of patients after allogeneic hematopoietic cell transplantation and is the leading cause of late morbidity, mortality and impaired quality of life. Besides steroids and calcineurin inhibitors, modalities to prevent or treat chronic GVHD are limited in Japan. Several clinical trials of newer modalities such as extracorporeal photopheresis, low-dose interleukin-2 and tamibarotene have been completed recently and await approval. In the symposium of the 39th JSHCT meeting, the current understandings in mechanistic biology of chronic GVHD and characteristics of chronic GVHD in the Japanese population were discussed. In addition, the results of transplant physician survey on the current practices in chronic GVHD management were discussed. The highlights included talks from international experts about most recent topics and discussion about future perspectives of chronic GVHD. This report summarizes contents of the symposium.