Paroxysmal nocturnal hemoglobinuria(PNH)is a clonal proliferative disease of hematopoietic stem cells that is clinically characterized by he-molysis,thrombosis,and bone marrow failure.In recent years,significant progr...Paroxysmal nocturnal hemoglobinuria(PNH)is a clonal proliferative disease of hematopoietic stem cells that is clinically characterized by he-molysis,thrombosis,and bone marrow failure.In recent years,significant progress has been made in the complement inhibitor-based treatment of PNH,but the only curative treatment is still hematopoietic stem cell transplantation(HSCT).This article reviews the research progress on al-logeneic HSCT for PNH,systematically summarizes the overview,indica-tions,influencing factors,and treatment outcomes of allogeneic HSCT for PNH,and provides an analysis of HSCT for PNH.展开更多
Allogeneic hematopoietic cell transplantation(Allo-HCT)is a curative therapy for hematologic malignancies owing to graft-versus-leukemia/lymphoma(GVL)activity mediated by alloreactive donor T cells,but graft-versus-ho...Allogeneic hematopoietic cell transplantation(Allo-HCT)is a curative therapy for hematologic malignancies owing to graft-versus-leukemia/lymphoma(GVL)activity mediated by alloreactive donor T cells,but graft-versus-host disease(GVHD)mediated by the donor T cells remains a major obstacle for a wide-spread clinical application of Allo-HCT.1 The GVHD target tissues are variable in different patients and can involve gastrointestinal(GI)track,liver,lung,skin,spleen,lymph nodes,thymus,and bone marrow(BM).2 Although the principal organs of acute GVHD are GI track,liver,and lung,BM GVHD can delay reconstitution of lymphohematopoietic cells,resulting in subsequent bleeding and infection that account for~30%of deaths after Allo-HCT.3 The pathogenesis of BM GVHD was proposed to result from damage of BM stroma niches by donor CD4+T cells in a Fas/FasL-dependent manner,and depletion of donor CD4+T cells effectively prevent BM GVHD.3,4 Besides direct suppression of primitive donor hematopoietic stem cells(HSCs)and blocking megakaryocyte differentiation,5 the cytokines(ie,GM-CSF,IFN-γ,and TNF-α)from donor T cells also inhibited HSC differentiation into regulatory plasmacytoid dendritic cells(DCs)that is important for immune tolerance.6 However,how BM GVHD impact on host-type stroma niches and their interactions with HSCs remains unclear,and a recent publication in JCI by Lin et al from joint groups of Xiaoxia Hu,Hui Cheng,Tao Cheng,and Weiying Gu has provided novel insights.展开更多
基金supported by the National Key Research and Development Program of China(N2023YFC2507803)Key Program of National Natural Science Foundation of China(82230004 and 82430006)+1 种基金Capital Health Development and Research of Special(2022-1-4082)Beijing Natural Science Foundation(7242154 and 7232188).
文摘Paroxysmal nocturnal hemoglobinuria(PNH)is a clonal proliferative disease of hematopoietic stem cells that is clinically characterized by he-molysis,thrombosis,and bone marrow failure.In recent years,significant progress has been made in the complement inhibitor-based treatment of PNH,but the only curative treatment is still hematopoietic stem cell transplantation(HSCT).This article reviews the research progress on al-logeneic HSCT for PNH,systematically summarizes the overview,indica-tions,influencing factors,and treatment outcomes of allogeneic HSCT for PNH,and provides an analysis of HSCT for PNH.
文摘Allogeneic hematopoietic cell transplantation(Allo-HCT)is a curative therapy for hematologic malignancies owing to graft-versus-leukemia/lymphoma(GVL)activity mediated by alloreactive donor T cells,but graft-versus-host disease(GVHD)mediated by the donor T cells remains a major obstacle for a wide-spread clinical application of Allo-HCT.1 The GVHD target tissues are variable in different patients and can involve gastrointestinal(GI)track,liver,lung,skin,spleen,lymph nodes,thymus,and bone marrow(BM).2 Although the principal organs of acute GVHD are GI track,liver,and lung,BM GVHD can delay reconstitution of lymphohematopoietic cells,resulting in subsequent bleeding and infection that account for~30%of deaths after Allo-HCT.3 The pathogenesis of BM GVHD was proposed to result from damage of BM stroma niches by donor CD4+T cells in a Fas/FasL-dependent manner,and depletion of donor CD4+T cells effectively prevent BM GVHD.3,4 Besides direct suppression of primitive donor hematopoietic stem cells(HSCs)and blocking megakaryocyte differentiation,5 the cytokines(ie,GM-CSF,IFN-γ,and TNF-α)from donor T cells also inhibited HSC differentiation into regulatory plasmacytoid dendritic cells(DCs)that is important for immune tolerance.6 However,how BM GVHD impact on host-type stroma niches and their interactions with HSCs remains unclear,and a recent publication in JCI by Lin et al from joint groups of Xiaoxia Hu,Hui Cheng,Tao Cheng,and Weiying Gu has provided novel insights.
