Analysis of mechanism of successful HLA-haploidentical stem cell transplantation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Hyogo Medical University
• Principal Investigator: OGAWA Hiroyasu 兵庫医科大学, 医学部, 教授 (80194447)
• Co-Investigator(Kenkyū-buntansha): OKADA Masaya 兵庫医科大学, 医学部, 講師 (00309452) ; KAIDA Katuzi 兵庫医科大学, 医学部, 助教 (00441254) ; IKEGAME Kazuhiro 兵庫医科大学, 医学部, 講師 (20372609) ; INOUE Takayuki 兵庫医科大学, 医学部, 助教 (20441256)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 造血幹細胞移植 / HLA半合致移植 / 移植片対宿主病 / 可溶性IL-2受容体 / 白血病 / 制御性T細胞

Outline of Final Research Achievements

We developed a new regimen for unmanipulated HLA-haploidentical stem cell transplantation using reduced intensity conditioning, low dose of anti-thymocyte globulin and steroids. As graft-versus-host disease is a major drawback in haploidentical transplantation, we found that soluble interleukin-2 receptor level on day 7 was important as a predictor of graft-versus-host disease. In a prospective multicenter trial, the rate of donor engraftment and survival on day 100 was 100% and 88.2%, respectively. These data showed that this regimen was safe and feasible.
To study cellular mechanisms of haploidentical transplantation, we independently developed a murine MHC-haploidentical stem cell transplantation model, and studied the kinetics of immune cells in mesenteric lymph nodes early in transplantation. As a result, host-derived regulatory T cells were found to negatively regulate host dendritic cells, resulting in inducing the tolerance between donor and recipients.

Free Research Field

造血幹細胞移植