Immunotherapy of murine leukemia following non-myeloablative conditioning with naïve or G-CSF mobilized blood or bone marrow stem cells

Allogeneic stem cell transplantation (SCT) is the treatment of choice for a large number of hematologic malignancies. Its major advantage over conventional chemotherapy lies in the graft-versus-leukemia (GVL) effects mediated by allo- or tumor-reactive donor lymphocytes given in the course of SCT or post transplantation as donor lymphocyte infusions (DLI). The benefits of cell-mediated immunotherapy over myeloablative radiochemotherapy have also made it possible to reduce the intensity of conditioning regimens. Mobilized peripheral blood has proved preferable to bone marrow (BM) as a source of stem cells for transplantation, since it provides a larger number of stem cells on the one hand and immunologically competent lymphocytes on the other. The use of granulocyte colony stimulating factor (G-CSF), which is necessary to mobilize and increase the number of stem cells, may down-regulate the GVL effect by suppression of donor effector T lymphocytes by inducing Th₁→Th₂ cytokine switch. It has previously been shown that GVL effects may be amplified by both in vivo and in vitro activation of donor lymphocytes with human recombinant interleukin-2 (rIL-2). Our studies using a leukemic murine model prepared for transplantation with low intensity conditioning prior to infusion of G-CSF-mobilized peripheral blood stem cells (PBSC) have demonstrated that mobilization of blood cells with G-CSF and in vivo treatment with rIL-2 following low-intensity conditioning enhances the GVL effects and prolongs survival of recipients inoculated with BCL1. Activation of donor lymphocytes with rIL-2 may thus be useful for amplifying GVL effects following mobilization with G-CSF.