ABSTRACT
Objective To evaluate the feasibility of secondary transplantation for patients with acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. Methods Two acute leukemia patients underwent the first haploidentical hematopoietic stem cell transplantation from two donors with thalassemia, and the number of collected CD34+ cells was 2.57×106/kg and 1.99×106/kg per donor, respectively. The first haploidentical hematopoietic stem cell transplantation failed. Secondary transplantation was performed from two non-thalassemia donors, and the number of collected CD34+ cells was 4.28×106/kg and 5.75×106/kg per donor, respectively. A reduced-intensity conditioning regimen consisting of fludarabine (Flu), busulfan (Bu) and antithymocyte globulin (ATG) was adopted for the secondary transplantation. Results For two recipients, the time of secondary transplantation of neutrophil and platelet was +12 d and +10 d, +10 d and +10 d, respectively. Up to the final follow-up (+1 062 d and +265 d after secondary transplantation), the primary diseases of both two recipients have been completely relieved without evident post-transplantation complications. Conclusions Secondary transplantation with reduced-intensity conditioning regimen may successfully treat acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation.
ABSTRACT
Objective To evaluate the effect of anti-RANTES monoclonal antibody in combination with ciclosporin (CsA)upon inhibiting the rejection response during secondary heart transplantation in mouse models. Methods BALB/c mouse models were used as the donors and C57BL/6 mice were utilized to establish secondary heart transplantation recipient models. The animals were randomly divided into the control (physiological saline,n =6 ),A (anti-RANTES monoclonal antibody treatment,n =6 ),B (CsA treatment,n =6 ) and C groups (anti-RANTES monoclonal antibody combined with CsA treatment,n=6). The survival time of heart after secondary transplantation was observed. The degree of acute heart rejection was assessed by histopathological analysis. The relative expression levels of RANTES,interleukin(IL)-2,IL-1 0,interferon(IFN)-γand transcription growth factor(TGF)-βmessenger ribonucleic acid (mRNA)in the heart grafts were quantitatively measured by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The serum levels of RANTES,IFN-γ,IL-2,IL-1 0 and TGF-βwere detected by enzyme-linked immune absorbent assay (ELISA). Results The heart grafts of all mice survived after secondary cardiac transplantation. Compared with the control group,the survival time of hearts in group A,B and C was significantly prolonged (all P<0. 01 ). Pathological staining revealed that the quantity of infiltrated inflammatory cells in group C was significantly decreased than those in the other groups. The expression levels of heart RANTES,IFN-γand IL-2 mRNA in group C were significantly down-regulated, whereas the expression levels of IL-1 0 and TGF-βmRNA were considerably up-regulated compared with those in the other three groups (all P<0. 05). The serum levels of RANTES,IL-2 and IFN-γin group C were significantly down-regulated, whereas the serum contents of IL-1 0 and TGF-βwere considerably up-regulated compared with those in the other three groups (all P<0. 05 ). Conclusions Combined application of anti-RANTES monoclonal antibody and CsA can effectively induce the immune tolerance to secondary cardiac transplantation and prolong the survival time of the cardiac grafts in mouse models.