Efficacy and security of a new cladribine-based conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with major thalassemia / 中华器官移植杂志

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 (range2-13 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 (range5 .72-12 .49 × 108/kg) and 12 .2 × 106/kg (range6 .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 (range8-17 days) and 13 days (range8-37 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 .