Allogeneic bone marrow transplantation and donor lymphocyte infusion in a mouse model of irradiation-induced myelodysplastic/myeloproliferation syndrome (MD/MPS): evidence for a graft-versus-MD/MPS effect
The role of graft-versus-malignancy reactivity in the effects of allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusion (DLI) for myelodysplastic syndromes is as yet not well established. Clinical data are limited and animal models are scarce. Here, we report on the effects of allogeneic bone marrow transplantation (BMT) and DLI in a novel model of irradiation-induced murine myelodysplastic /myeloproliferation syndrome (MD/MPS).
Total body irradiation with 8.5 Gray in SJL/J mice gave rise to a lethal wasting syndrome in 60% of mice, characterized by 1° normocellular bone marrow with dysplastic features in erythroid, myeloid and megakaryocytic cell lineages, 2° lymphosplenomegaly with spleens harboring a prominent extramedullary hematopoiesis with erythroid, myeloid and megakaryocytic lineages exhibiting dysplastic features, and foci of dysplastic hematomyelopoiesis in the liver, 3° peripheral thrombocytopenia, and 4° evidence of disseminated infection or leukemic transformation in selected animals. This clinicopathological picture was consistent with a murine form of MD/MPS. Syngeneic or allogeneic (BALB/c) T cell depleted BMT could not prevent the occurrence of lethal MD/MPS. In contrast, DLI at week 2-4 after BMT led to restoration of the dysbalanced hematomyelopoiesis. However, severe DLI-induced acute graft-versus-host disease occurred, precluding a survival advantage.
We present evidence of the existence of a post allogeneic BMT DLI-induced graft-versus-MD/MPS effect in murine irradiation-induced MD/MPS.