Superior Outcome Using Cyclosporin A Alone Versus Cyclosporin A Plus Methotrexate for Post-Transplant Immunosuppression In Children with Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation.

Abstract 4502

Graft-versus-host disease (GVHD) is a major complication and one of the main causes of death after hematopoietic stem cell transplantation (HSCT). The GVHD prophylaxis influences the incidence of GVHD, relapse rate, and patient's survival. GVHD is associated with graft-versus-leukemia effect, which is mediated by donor T lymphocytes and decreases the risk of relapse. Therefore, a reduced post-transplant immunosuppression might have a positive impact on patient's survival. The outcome of different immunosuppressive prophylaxis regimen for adult patients has been studied extensively, whereas the effect on children has yet to be determined. Therefore, we performed a retrospective study analyzing 62 children (median age, 11 years) with acute lymphoblastic leukemia (n=35) or acute myeloid leukemia (n=27) who underwent bone marrow (n=56), peripheral blood stem cell (n=4), or umbilical cord blood (n=2) transplantation in a single center between November 1984 and July 2008. All respective donors were HLA-identical siblings. The patients received an immunosuppressive prophylaxis consisting of cyclosporin A (CSA) plus methotrexate (MTX) (n=43) or cyclosporin A alone (n=19). Patients in the CSA+MTX arm received CSA at a total dose of 10 mg/kg/day on day -1, 5mg/kg/day on days 0 to 4, and 3 mg/kg/day starting on day 5, and in addition MTX at a dosage of 10 mg/m² on days 1, 3, 6, and 11. The 19 patients in the CSA arm received CSA at a total dose of 3 mg/kg/day starting on day -1. Concerning the patient's gender, age, diagnosis, and state of remission prior to transplantation, the two groups did not differ significantly. Patients who received CSA alone as post-transplant immunosuppression had a significantly reduced cumulative incidence of relapse (5% versus 40%; p=0,002), a significantly increased 5-year event-free survival (84% versus 35%; p=0.001), and a significantly increased 5-year overall survival (84% versus 42%; p=0.004). Interestingly, the incidence of acute GVHD grade II-IV in patients in the CSA arm was equivalent to the CSA+MTX arm (26% versus 19%; p=0.440). In addition, we did not observe a significant difference in the cumulative incidence of chronic GVHD (32% in the CSA arm versus 23% in the CSA+MTX arm; p=0.428). There was also no significant difference in the cumulative incidence of treatment related mortality after 1 year (10% in the CSA arm versus 23% in the CSA+MTX arm; p=0.165). In conclusion, CSA alone for post-transplant immunosuppression allows a stronger graft-versus-leukemia effect and thereby reduces the relapse rate and the number of patients dying of leukemia effectively without increase of acute and chronic GVHD. Post-transplant immunosuppression consisting of CSA alone leads to a superior outcome and should be preferred in children with a HLA-identical sibling as donor.