Bi-Specific T Cell Therapy for Pancreatic Cancer

Abstract

Objective: We have previously reported that an HLA 8 of 8 allele-matched unrelated donor (8/8 MUD) is superior to a related donor with HLA-1 antigen mismatch in the graftversus-host (GVH) direction (RD/1AG-MM-GVH) in transplantation for leukemia (Kanda J, et al. Blood 2012). However, the risk of relapse during the unrelated donor coordination period biases this comparison. Therefore, we performed decision analysis of donor selection in allogeneic stem cell transplantation for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in first remission (CR1); this method can consider various factors including risk of relapse during the donor coordination period and the decrease in quality of life (QOL) as a result of chronic graft-versus-host disease (GVHD). Methods: The incidences of relapse during the coordination period of 8/8MUD or RD/1AG-MM-GVH were estimated using the data from published studies on chemotherapeutic treatment for AML and ALL. Transition probabilities after transplantation were estimated using the database of the Transplant Registry Unified Management Program for the Japan Society for Hematopoietic Cell Transplantation. The expected 5-year survival probabilities with or without QOL adjustments were estimated using TreeAgePro software. One-way sensitivity analysis was performed by varying each transition-probability value within its plausible range. Results: In transplantation for AML-CR1, the expected 5-year survival probability was higher on selection of 8/8MUD than RD/1AG-MM-GVH (59% vs. 47%), and this superiority remained unchanged by sensitivity analysis of various factors, including the interval between achievement of CR1 and actually receiving transplantation. In transplantation for ALL-CR1, the 5-year survival probability was higher on selection of 8/8 MUD (48% vs. 43%). In one-way sensitivity analysis, the 5-year survival probability was higher on selection of RD/1AG-MM-GVH when the interval between CR1 and 8/8 MUD transplantation was !7 months. However, 8/8 MUD was superior after QOL adjustments. If the 5-year survival rate was increased by 3% (7% after QOL adjustment) in transplantation using RD/1AG-MM-GVH, the merit of selecting RD/1AG-MM-GVH outweighs that of 8/8 MUD. Conclusions: 8/8 MUD should be prioritized in transplantation for AML-CR1. In transplantation for ALL-CR1, RD/1AG-MM-GVH should be prioritized only when the interval between CR1 and 8/8 MUD transplantation is expected to be long. However, MUD should be prioritized if QOL is considered.