In vitro purging of bone marrow with mafosfamide synergizes with in vivo chemotherapy to delay the hematological recovery in a murine model of autologous bone marrow transplantation.

Very long-lasting leukopenias and thrombocytopenias have been observed in patients submitted to transplantation of autologous bone marrow incubated in vitro with cyclophosphamide derivatives. With the aim of evaluating the contribution of in vitro exposure of bone marrow to mafosfamide (Asta-Z) and of in vivo chemotherapy given before bone marrow collection in these cytopenias, we designed a murine model of syngeneic bone marrow transplantation including treatment of donor and recipient mice with high doses of cyclophosphamide and in vitro exposure of the bone marrow transplant to Asta-Z. Blood platelets and leukocytes, medullary splenic colony forming unit (CFU-S), committed megacaryocytic (CFU-Meg) and granulomacrophagic (CFU-GM) precursor cell recovery was followed up to 56 days posttransplant. The data indicate that in vitro exposure of bone marrow to Asta-Z before reinfusion increases the delay in platelet recovery already induced by the chemotherapy given to donor mice and is specifically responsible for the prolongation of leukopenia. In recipient bone marrow, a synergy between the ablative effect of the in vitro treatment of bone marrow graft and the chemotherapy given to donors and recipients on CFU-S, CFU-Meg and CFU-GM was found.