Project description:This phase II trial studies how well giving fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil and total-body irradiation together with a donor bone marrow transplant works in treating patients with high-risk hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells by stopping them from dividing or killing them. Giving cyclophosphamide after transplant may also stop the patient’s immune system from rejecting the donor’s bone marrow stem cells. The donated stem cells may replace the patient’s immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body’s normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening
Project description:RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation in treating patients who have hematologic cancer.
Project description:After irradiation and bone-marrow transplantation, most of microglia and boarder-associated macrophages in the central nervous system is replaced by engranft cells. Taking advantages of Ms4a3-Cre: R26-TdTomato: Cx3cr1-gfp mice, we discriminated cells from monocyte precursors and hematopoietic stem cells with colors at 32 weeks following irradiation and bone-marrow transplantation. We sorted HSC-derived, monocyte-derived, and endogenouse microglia and leptomeningeal macrophages, and analyzed gene expression level between different cell populations using a bulk RNAseq method.
Project description:This phase I clinical trial is studying the side effects and the best dose of lenalidomide after donor bone marrow transplant in treating patients with high-risk hematologic cancer. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing.
Project description:EAE is a chronic demyelinating condition characterized by central nervous system immune infiltration. Spinal cord injury results in damage to the spinal cord, partially due to leukocyte infiltration and inflammatory contributions. Here we performed single-cell RNA-sequencing of spinal cord tissue to examine how CNS-infiltrating cells from different niches may play distinct roles in different disease pathogenesis.
Project description:Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare, extranodal lymphoma. Primary vitreo-retinal lymphoma (PVRL) occurs in 15-25% of PCNSL. CNS involvement also occurs in systemic diffuse large B-cell lymphoma, termed secondary central nervous system lymphoma (SCNSL). Despite intensive treatment, patient outcomes are poor when compared to DLBCL without CNS involvement. How and why lymphoma cells home to the CNS and vitreo-retinal compartment remains unknown. In vivo models to study lymphoma cell tropism are urgently needed. We therefore established and characterized 3 primary and 4 secondary patient-derived CNS lymphoma xenograft mouse models using immunohistochemistry, flow cytometry and nucleic acid sequencing technology. In spleen reimplantation experiments, we characterized the dissemination pattern of orthotopic and heterotopic xenografts and performed RNA sequencing to detect differences on the transcriptome level. Moreover, we found that lymphoma cells in PCNSL xenografts home to the eye after intrasplenal implantation in around 60% of cases, similar to PVRL. This in vivo tumor model preserves key features of this rare lymphoma entity and can be used to explore pathways that are critical for CNS and retinal tropism with the goal to find potential new targets for novel therapeutic approaches .
Project description:Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare, extranodal lymphoma. Primary vitreo-retinal lymphoma (PVRL) occurs in 15-25% of PCNSL. CNS involvement also occurs in systemic diffuse large B-cell lymphoma, termed secondary central nervous system lymphoma (SCNSL). Despite intensive treatment, patient outcomes are poor when compared to DLBCL without CNS involvement. How and why lymphoma cells home to the CNS and vitreo-retinal compartment remains unknown. In vivo models to study lymphoma cell tropism are urgently needed. We therefore established and characterized 2 primary and 2 secondary patient-derived CNS lymphoma xenograft mouse models using immunohistochemistry, flow cytometry and nucleic acid sequencing technology. In spleen reimplantation experiments, we characterized the dissemination pattern of orthotopic and heterotopic xenografts and performed RNA sequencing to detect differences on the transcriptome level. Moreover, we found that lymphoma cells in PCNSL xenografts home to the eye after intrasplenal implantation in around 60% of cases, similar to PVRL. This in vivo tumor model preserves key features of this rare lymphoma entity and can be used to explore pathways that are critical for CNS and retinal tropism with the goal to find potential new targets for novel therapeutic approaches .