Bone Marrow Transplantation in the Rat

We have analysed the cytological structure of inflammation in the different parenchymal target organs during acute graft-versus-host disease after bone marrow transplantation in the rat. Inflammation (recovery of increased numbers of white cells) was recorded in the liver, skin, and lungs of the allograft recipient compared with the syngeneic graft recipient from day 5 onwards, accompanied by reduced recovery of inflammatory cells from the gut. The major cytological manifestation of the disorder was an increase in the total number of blast cells, large granular lymphocytes (LGL), and lymphocytes in the liver and skin, and of the number of blast cells and LGL in the lung. At the same time, a depletion of LGL and lymphocytes was recorded in the blood, suggesting migration of these cell components to the site of inflammation.     

Acceleration of Immune Reconstitution after Bone Marrow Transplantation in Mice by Bone Marrow Stromal Cell Line Transfected with IL-6 Gene

After bone marrow transplantation, dysfunction of immunesystem is a critical problem to be resolved in clinical treat ment. Efficient bone marrow transplantation needs com pleted immune reconstitution, which is associated to manyfactors. Among them, Chemo/radiotherapy after and/orbefore BMT can cause great damage to hematopoietic mi croenvironment, which decrease the ability of proliferationand differentiation of stem cell[1]. To observe the effectof bone marrow stromal cell on the imm…     

Lymphocyte Chimerism After Bone Marrow Transplantation

Specific HLA antibodies were used to eliminate donor and recipient cells, respectively, from lymphocyte suspensions prepared from the blood of a child who had been transplanted with bone marrow from an HLA-A- and HLA-B-incompatible, HLA-D-compatible donor. About 70% of the lymphocytes were of donor HLA type, the remaining of recipient type. The phytohemagglutinin-responsive lymphocytes were exclusively limited to the lymphocyte population carrying donor-type HLA antigens. Membrane immunofluorescence investigations of the donor and recipient populations showed a low percentage of IgM-positive lymphocytes in the donor population and an extremely high proportion of IgM-positive lymphocytes in the recipient population. About 90% of the donor lymphocytes were T cells, as judged by their capacity to form rosettes between sheep erythrocytes and T lymphocytes; no cells in the recipient cell population expressed this ability.     

Acceleration of Immune Reconstitution after Bone Marrow Transplantation in Mice by Bone Marrow Stromal

To observe potential effect of the engineered bone marrow stromal cell line QXMSC1 secreting IL-6 (QXMSCIL-6) on accelerating immnune reconstitution in syngeneic bone marrow transplantation in mice, QXMSC1 was transfected with the eukaryocytic expression vector pcDNAIL-6, which contained hIL-6 cDNA by liposome-mediated gene transfecting technique. G418-resistance clone was selected by limiting dilution. The highest secreting clone was selected by ELISA assay and used in animal experiments. The recipient mice (BALB/c) were lethally irradiated and cotransplanted syngeneic bone marrow (10^7/mice) and the QXMSCIIL-6 (5×10^5/mice). Lymphocyte proliferation induced by ConA and LPS, helper T lymphocyte precursor (HTLp), cytotoxic T lymphocyte precursor (CTLp), plaque-forming cell (PFC), delayed type hypersensitivity (DTH) were examined 30, 60 days in post transplantation respectively. The results showed that lymphocytes proliferation to ConA and LPS, HTLp, CTLp increased, DTH and PFC were improved by cografted stromal cells QXMSCIIL-6 on 30, 60 days after BMT. These results demonstrated that the bone marrow stromal cell line QXMSC1 IL-6 transfected with IL-6 (QXMSC11L-6) accelerated immnune reconstitution in syngeneic bone marrow transplantation.     

Immunodeficiency after Allogeneic Bone Marrow Transplantation in Man

This study was undertaken to clarify the mechanism behind the severely decreased lymphocyte proliferative response upon stimulation with mitogens and antigens seen after allogeneic bone marrow transplantation (BMT) in man. We investigated eight BMT patients and eight controls and found that the proliferative response of patient cells was reduced both when the cells were stimulated with phytohaemagglutinin (PHA) and when they were stimulated with a combination of phorbol myristate acetate (PMA), which is an activator of protein kinase C (PKC), and the calcium ionophore A23187, which irreversibly opens for calcium transport into the cell (median relative responses were 41 and 37%, respectively). However, the PHA-induced increase in the concentration of intracellular free calcium in post-BMT cells was not significantly different from the values found in control cells and the expression of interleukin 2 (IL-2) receptors (CD25) was only slightly decreased. However, the production of IL-2 was severely decreased in patient cells after stimulation with A23187/PMA (median 3541 units), although it was higher than in PHA-stimulated control cells (median 354 units). These results show that a direct activation of PKC by PMA combined with an increase in intracellular free calcium by A23187 cannot overcome the lymphocyte proliferation deficiency in cells from patients after allogeneic BMT. The data suggests that the defect is affecting the diacylglycerol pathway considerably more than the inositol triphosphate pathway.     

Family Studies of Neutrophil Alloantigens in Bone Marrow Transplantation

In order to evaluate the utility of the neutrophil specific antigens NA1, NA2, Vaz (NC1), NB1 and 9a in the documentation of bone marrow chimeras in recipients of allogeneic bone marrow grafts, neutrophil antigen typing was performed by EDTA microagglutination on the families of 17 patients with hematopoietic disorders under evaluation for bone marrow transplantation. Mendelian segregation independent of HLA and mutually independent was noted for the NA, NB and 9a systems. Vaz (NC1) segregated with and was included in NA2. Serological complexity was noted for NA1 and NA2. Typing for neutrophil antigens was achieved for 13 of 17 patients. Eight of 10 pateints with HLA identical siblings had neutrophil antigen markers differing between donor and recipient. Conversion to donor neutrophil phenotype was documented for four recipients of bone marrow grafts. The neutrophil antigens, particularly of the NA system, appear to be useful additional markers for allogeneic bone marrow engraftment.     

Recovery of Natural Cytotoxicity After Bone Marrow Transplantation

Reconstitution of non-MHC restricted cytotoxicity was followed in 7 and in 4 cases after auto-and allotransplantation, respectively. In autografted cases a high level of natural cytotoxicity, which exceeded the pre-transplant values, was seen at the beginning of hematological reconstitution. At that time, the high percentage of DR+ peripheral blood mononuclear cells (PBMC) was found, while the percentage of CD16+ cells was in the range of the pre-transplant values. A high level of cytotoxicity was a transient phenomenon. In all cases, 40 days after grafting the natural cytotoxicity was again in the range of the pre-transplant values. In allotransplantation the peak of cytotoxicity was seen soon after the beginning of hematological recovery and the activity decreased after 24 to 48 days after grafting.     

Recovery of Natural Cytotoxicity After Bone Marrow Transplantation

Reconstitution of non-MHC restricted cytotoxicity was followed in 7 and in 4 cases after auto-and allotransplantation, respectively. In autografted cases a high level of natural cytotoxicity, which exceeded the pre-transplant values, was seen at the beginning of hematological reconstitution. At that time, the high percentage of DR+ peripheral blood mononuclear cells (PBMC) was found, while the percentage of CD16+ cells was in the range of the pre-transplant values. A high level of cytotoxicity was a transient phenomenon. In all cases, 40 days after grafting the natural cytotoxicity was again in the range of the pre-transplant values. In allotransplantation the peak of cytotoxicity was seen soon after the beginning of hematological recovery and the activity decreased after 24 to 48 days after grafting.     

Patient Perspectives Regarding Allogeneic Bone Marrow Transplantation in Myelofibrosis

Hematopoietic stem cell transplantation (HCT) is a curative treatment for patients with myelofibrosis (MF); however, many HCT-eligible patients decline this potentially life-saving procedure. The reasons behind this decision are not clear. We sought to survey patients with MF to understand their perspective on HCT. A 63-question survey was posted on myeloproliferative neoplasm patient advocacy websites. A total of 129 patients with MF responded to the survey. Among these patients, 49 (41%) were referred for HCT, and 41(32%) attended the transplantation consult. Of the patients who attended the transplantation consult, 24 (59%) did not plan on going on to HCT, and 16 (41%) intended to proceed with HCT. Reasons for the decision to not undergo transplantation included the desire to not be ill, desire to not spend time in the hospital, and concerns about overall quality of life. Specifically, concerns related to financial impact and the risk of graft-versus-host disease (GVHD) were expressed. Patients who decided to proceed with HCT felt that this would extend their survival and allow them to be around family for longer. This is the first survey to investigate patient perceptions regarding HCT for MF. Less than one-half of the patients were referred for HCT, and of those, less than one-half planned on proceeding with the transplantation, suggesting that many patients do not receive this life-saving procedure. Further exploration of the basis of patients’ reluctance to proceed with HCT is warranted.