ABSTRACT
Objective@#To observe the efficacy and safety of intensive cladribine-based conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with major thalassemia.@*Methods@#Retrospective analysis was performed for the clinical data of 12 children with major thalassemia undergoing allo-HSCT from March 2017 to July 2018. All of them were diagnosed definitely and the median age at transplantation was 5 years (range: 2-13 years), including HSCT from HLA-matched unrelated donor (n=8), HLA8/10-matched unrelated donor (n=1), HLA-matched sibing donor (n=2) and haploidentical donor (n=1). They received a new intensive conditioning regimen of cyclophosphamide (CTX), cladribine, busulfan (Bu) and antithymocytic globulin. The median doses of mononuclear cell (MNC) and CD34 positive cell were 10.97×108/kg (range: 5.72-12.49×108/kg) and 12.2×106/kg (range: 6.7-22×106/kg). Graft-versus-host disease (GVHD) was prevented by cyclosporine A (CSA), methotrexate (MTX) and mycophenolate mofetil (MMF).@*Results@#Engraftment succeeded (n=11) and failed (n=1). The median time of neutrophil and platelet engraftment was 11 days (range: 8-17 days) and 13 days (range: 8-37 days) respectively. There were grade II acute GVHD (n=6) and grade IV intestinal acute GVHD (n=1) at 35 days post-transplantation. The latter one finally died of severe infection at 70 days post-transplantation. Two recipients of DLI developed limited chronic GVHD. Three cases (25%) developed cytomegaloviremia. None suffered from severe transplantation-related complications, such as cytomegalovirus diseases, hepatic veno-occlusive disease (HVOD), hemorrhagic cystitis or septicemia, etc. The median follow-up time was 15(8-18) months. Among 11 survivors, ten became transfusion-independent.@*Conclusions@#Cladribine-based conditioning regimen is both safe and effective for allo-HSCT in children with major thalassemia. However, vigorous immunosuppression may increase the risks of infection and viral activation after transplantation.
ABSTRACT
Objective To observe the efficacy and safety of intensive cladribine-based conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT ) in children with major thalassemia .Methods Retrospective analysis was performed for the clinical data of 12 children with major thalassemia undergoing allo-HSCT from March 2017 to July 2018 .All of them were diagnosed definitely and the median age at transplantation was 5 years (range:2-13 years ) , including HSCT from HLA-matched unrelated donor (n= 8 ) , HLA8/10-matched unrelated donor (n=1) ,HLA-matched sibing donor (n=2) and haploidentical donor (n=1) .They received a new intensive conditioning regimen of cyclophosphamide (CTX ) , cladribine , busulfan (Bu ) and antithymocytic globulin .The median doses of mononuclear cell (MNC) and CD34 positive cell were 10 .97 × 108/kg (range:5 .72-12 .49 × 108/kg) and 12 .2 × 106/kg (range:6 .7-22 × 106/kg) .Graft-versus-host disease (GVHD) was prevented by cyclosporine A (CSA) ,methotrexate (MTX) and mycophenolate mofetil (MMF) .Results Engraftment succeeded (n= 11) and failed (n= 1) .The median time of neutrophil and platelet engraftment was 11 days (range:8-17 days) and 13 days (range:8-37 days) respectively .There were grade II acute GVHD (n= 6) and grade IV intestinal acute GVHD (n=1) at 35 days post-transplantation .The latter one finally died of severe infection at 70 days post-transplantation .Two recipients of DLI developed limited chronic GVHD .Three cases ( 25％ ) developed cytomegaloviremia . None suffered from severe transplantation-related complications , such as cytomegalovirus diseases , hepatic veno-occlusive disease ( HVOD ) , hemorrhagic cystitis or septicemia ,etc .The median follow-up time was 15(8-18) months .Among 11 survivors ,ten became transfusion-independent .Conclusions Cladribine-based conditioning regimen is both safe and effective for allo-HSCT in children with major thalassemia . However , vigorous immunosuppression may increase the risks of infection and viral activation after transplantation .
ABSTRACT
To investigate the role of immediate-early gene c-fos in sodium selenite-induced apoptosis and its position in a possible cascade of apoptogenic genes, we compared the time-courses of expression for 5 related genes, including c-fos, during the apop- tosis induced by sodium selenite with or without blockage of c-fos expression by adding c-fos antisense oligodeoxynucleotide ( ASO) in cultured cortical neurons. The results showed that: (1) in control experiments without c-fos ASO adding, 0. 5 μmol/ L sodium selenite-induced apoptosis as revealed by electrophoretic and flow cytometric examinations; at the same time, sodium selenite also induced down-regulation of bcl-2 mRNA expression and up-regulations of mRNAs related to bax, c-fos, p53, and acetylcholinesterase (AChE) genes; (2) in similar experimental conditions with c-fos ASO cotreatment, the sodium selenite-in- duced apoptosis was blocked with the up-regulation of p53 expression still emerging as before, while the changes in expressions of bcl-2, bax, AChE genes were reversed at the same time. The results suggest that c-fos ASO could play a protective role upon cortical neurons from suffering apoptosis induced by sodium selenite, and there might exist a cascade of gene expressions with p53 and c-fos genes being regulated upstream and then bcl-2, bax, and AChE genes being regulated downstream.