Efficacy and security of a new cladribine-based conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with major thalassemia

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. Key words: Hematopoietic stem cell transplantation; Thalassemia; Pretreatment