Macrophage colony-stimulating factor enhances rituximab-dependent cellular cytotoxicity by monocytes

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1644号 , 学位授与年月日 : 平成20年2月6日, 学位授与大学 : 金沢大学, 主査教授 : 金子 周一, 副査教授 : 向田 直史 , 須田 貴

Macrophage colony-stimulating factor enhances rituximab-dependent cellular cytotoxicity by monocytes

医薬保健研究域医学系Recent studies suggest that monocytes are the dominant effectors by which rituximab induces cell death in B-cell lymphoma. Because macrophage colony-stimulating factor (M-CSF) can enhance the cytotoxicity of monocytes, the authors examined whether this growth factor can enhance their ability to kill lymphoma cells in vitro. Monocytes derived from a healthy volunteer were cultured for 48 h in the presence or absence of M-CSF. Monocytes stimul ated with M-CSF were significantly more cytotoxic to Daudi B-cell lymphomas than unstimulated monocytes. Flow cytometry revealed that M-CSF increased monocyte expression of Fcγ receptors III and I by 1.6- and 1.5-fold, whereas the expression of Fcγ receptor II remained unchanged. These results suggest that pretreatment with M-CSF can improve the therapeutic efficacy of rituximab against intractable CD20+ lymphoma. © 2007 Japanese Cancer Association

Living-donor lobar lung transplantation for broncho-bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation: does bronchiolitis obliterans recur in transplanted lungs?

金沢大学付属病院血液内科We report a successful case of living-donor lobar lung transplantation (LDLLT) for therapy-resistant broncho-bronchiolitis obliterans (BBO) after allogeneic hematopoietic stem cell transplantation (HSCT). Bronchiolitis obliterans (BO) is one of the late-onset noninfectious pulmonary complications that occur after allogeneic HSCT and is usually resistant to immunosuppressive therapy. A 17-year-old girl with acute lymphoblastic leukemia (ALL) had undergone allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling in 1997. Five years later, she relapsed with ALL and was treated with chemotherapy following stem cell rescue and donor lymphocyte infusion from the original BMT donor. Eight months later, BBO resistant to immunosuppressive therapies, including rituximab, developed in combination with chronic graft-versus-host disease (GVHD). In February 2004, the patient underwent LDLLT from 2 other family members who were mismatched at 3 HLA loci. The patient has been in good health for more than 30 months following LDLLT and shows no sign of BBO in the transplanted lungs, just as with other patients who have undergone lung transplantation for BO associated with chronic GVHD. LDLLT may therefore be considered a viable therapeutic option for the treatment of BO after allogeneic HSCT