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

• Published in: Leukemia Vol. 23; no. 2; pp. 340 - 349
• Main Authors: Sprangers, B, Van Wijmeersch, B, Luyckx, A, Sagaert, X, De Somer, L, Rutgeerts, O, Lenaerts, C, Landuyt, W, Boeckx, N, Dubois, B, De Wolf-Peeters, C, Waer, M, Billiau, A D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2009; Nature Publishing Group
• Subjects: Anemia; Animal models; Animals; Biological and medical sciences; Bone marrow; Bone Marrow Transplantation; Cancer Research; Care and treatment; Case reports; Critical Care Medicine; Disease Models, Animal; Disseminated infection; Graft versus host disease; Graft versus host reaction; Graft vs Leukemia Effect; Grafting; Hematologic and hematopoietic diseases; Hematology; Hematopoiesis; Hematopoietic stem cells; Intensive; Internal Medicine; Irradiation; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Transfusion; Lymphocytes; Lymphocytes T; Malignancy; Medical sciences; Medicine; Medicine & Public Health; Mice; Mortality; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - therapy; Myeloproliferation; Myeloproliferative Disorders - therapy; Oncology; original-article; Remission (Medicine); Risk factors; Stem cell transplantation; Stem cells; Syngeneic grafts; Thrombocytopenia; Transplantation; Transplantation, Homologous; Treatment Outcome; Whole-Body Irradiation; Belgium; MD/MPS; mouse; alloHSCT; donor lymphocyte infusion; Animal model; Stem cell; Hematopoietic cell; Homograft; Myelodysplastic syndrome; Immunotherapy; Bone marrow; Graft; Adoptive immunization; Hematology; Donor lymphocyte infusion; Rodentia; Malignant hemopathy; Vertebrata; Mammalia; Treatment; Donor; Mouse; Animal; Irradiation; Lymphocyte; Comparative study; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2008.298

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 (alloBMT) and DLI in a novel model of irradiation-induced murine myelodysplastic/myeloproliferation syndrome (MD/MPS). Total body irradiation with 8.5 Gy 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 weeks 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-alloBMT DLI-induced graft-versus-MD/MPS effect in murine irradiation-induced MD/MPS.