ABSTRACT
BACKGROUND: Mortality in children with acute leukemias or MDS after allogeneic stem cell transplantation (allo-SCT) is mostly determined by relapses. It was recently shown by us that patients who develop increasing quantities of autologous hematopoietic cells in peripheral blood (increasing mixed chimerism, in-MC) after allo-SCT do significantly more often relapse (P < 0.0001) than patients with a complete chimerism (CC). In a small series of patients with in-MC, the relapse rate could be significantly reduced by administration of donor lymphocytes (DLI). METHODOLOGY: A prospective multicenter study was initiated under the question whether number of relapses can be significantly reduced either by withdrawal of post-transplant immunosuppression and/or by DLI in the critical stage of in-MC. RESULTS: Highly repetitive determination of the genetic status of 114 children with acute leukemias or MDS (ALL: n = 41, AML: n = 39, MDS: n = 34) revealed 55 cases with CC and 43 with in-MC. Relapses occurred significantly (P < 0.0001) more often in patients with in-MC (25/43) than in patients with CC (12/55). In-MC-patients showed a significantly (P < 0.01) enhanced event free survival rate (11/24) when DLI was given and/or post-transplant immunosuppression was stopped compared to patients which did not receive such an interventional regimen (1/19). Two in-MC-patients developed fatal GVHD after immunological intervention. CONCLUSION: These data substantiate that prophylactic immunotherapy on the basis of in-MC is a powerful treatment approach to suppress relapses of acute leukemias and MDS after allo-SCT.
