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PubMed1978

Heterotopically induced bone marrow. The concentration of hemopoietic stem cells in the induced bone marrow and its ability to repopulate lethally irradiated recipients.

Bone marrow induced in mice by xenogeneic epithelia of human amnion established cell line and of dog transitional epithelium seems to contain hemopoietic stem cells in the same concentration as orthotopic bone marrow. The induced bone marrow is able to protect lethally irradiated syngeneic recipients when used in the same doses as orthotopic one.

Amnion↗
PubMed1991

Bone marrow transplantation activity in Europe 1990. European Group for Bone Marrow Transplantation (EBMT)

During 1990 143 teams in 20 European countries performed a total of 4234 bone marrow transplants. Donor source was in 1802 cases an HLA-identical family donor, in 118 cases a non-identical family donor, in 36 cases a twin donor, in 181 an unrelated volunteer donor and in 2097 cases autologous bone marrow. Indications for the transplant were leukaemias in 2365 patients, lymphoproliferative disorders in 1104 patients, solid tumours in 382 patients, aplastic anaemia and thalassaemia in 281 patients, inborn errors in 58 patients and miscellaneous disorders in 44 patients. This survey of the European Group for Bone Marrow Transplantation on transplant activity clearly indicates that within the last decade bone marrow transplantation has become an established therapy in Europe. The results of this first complete survey provide a basis for planning therapeutic trials and health policy strategies.

Anemia, Aplastic↗
PubMed1998

Myeloid and lymphoid recovery following allogeneic bone marrow transplantation: a comparative study between related, unrelated bone marrow and allogeneic peripheral stem cell transplantation.

We studied myeloid and lymphoid recovery during a period of 12 months following HLA matched allogeneic bone marrow transplantation (BMT) in 15 patients. Patients were divided into three groups. Each group contained 5 patients according to the source of hematopoietic stem cell transplantation (HST): 1) related bone marrow transplantation (BMT), 2) allogeneic peripheral blood stem cell transplantation (PBSCT) and 3) matched unrelated donor transplantation (MUD). The rate and pattern of recovery of granulocytes, lymphocytes (T-cell subsets, B-cells, NK cells, subsets of CD45) were studied by cell counting and flow cytometry. Our results suggest faster recovery of PMN after PBSCT. Higher CD4 cell counts observed in the PBSCT group may have an impact on a lower incidence of opportunistic infections. Chronic GvHD mediated GvL effect seems to be more important in blood stem cell transplanted patients and this may have an influence on disease free survival.

Adult↗
PubMedDate not supplied

Do changes in bone marrow pressure contribute to the egress of cell from bone marrow?

Pressure was measured in the femoral medullary cavity of rabbits whose femoral muscles were subjected to electrostimulation. After electrostimulation the pressure in the medullary cavity increased fivefold. In groups of experimental animals the number of reticulocytes leaving the bone marrow and the number of reticulocytes in the peripheral blood were determined and it was observed that electrostimulation was followed by a severalfold rise in the amount of reticulocytes in both the bone marrow and the peripheral blood. The authors found that a great role in the egress of reticulocytes from the bone marrow into the circulation is played by regulation of the pressure in medullary cavity effected by changes in blood flow through the bone marrow.

Animals↗
PubMed1986

Recipient immune-competent T lymphocytes can survive intensive conditioning for bone marrow transplantation.

Bone marrow transplantation is usually preceded by intensive chemotherapy and radiation therapy designed to completely eliminate recipient immune-competent cells that might reject the donor bone marrow. We show that seven of 14 bone marrow transplant recipients who received intensive conditioning retained circulating T lymphocytes that proliferate after incubation with interleukin 2 and phytohemagglutinin and function as effector cells in an in vitro model of graft rejection. These T cells may mediate graft rejection.

Adult↗
PubMed1999

Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry.

BACKGROUND AND METHODS: It is uncertain whether mortality rates among patients who have undergone bone marrow transplantation return to the level of the mortality rates of the general population. We analyzed the characteristics of 6691 patients listed in the International Bone Marrow Transplant Registry. All the patients were free of their original disease two years after allogeneic bone marrow transplantation. Mortality rates in this cohort were compared with those of an age-, sex-, and nationality-matched general population. Cox proportional-hazards regression was used to identify risk factors for death more than two years after transplantation (late death). RESULTS: Among patients who were free of disease two years after transplantation, the probability of living for five more years was 89 percent (95 percent confidence interval, 88 to 90 percent). Among patients who underwent transplantation for aplastic anemia, the risk of death by the sixth year after transplantation did not differ significantly from that of a normal population. Mortality remained significantly higher than normal throughout the study among patients who underwent transplantation for acute lymphoblastic leukemia or chronic myelogenous leukemia and through the ninth year among those who underwent transplantation for acute myelogenous leukemia. Recurrent leukemia was the chief cause of death among patients who received a transplant for leukemia, whereas chronic graft-versus-host disease was the chief cause among those who received a transplant for aplastic anemia. Advanced, long-standing disease before transplantation and active chronic graft-versus-host disease were important risk factors for late death. CONCLUSIONS: In patients who receive an allogeneic bone marrow transplant as treatment for acute myelogenous or lymphoblastic leukemia, chronic myelogenous leukemia, or aplastic anemia and who are free of their original disease two years later, the disease is probably cured. However, for many years after transplantation, the mortality among these patients is higher than that in a normal population.

Adolescent↗
PubMed1996

A novel bone marrow frozen section assay for studying hematopoietic interactions in situ: the role of stromal bone marrow macrophages in erythroblast binding.

Bone marrow macrophages are found in intimate contact with erythroblasts. Exact mechanisms and functions of this interaction are unclear. New insights into erythroblast binding were obtained using a newly developed bone marrow frozen section assay. This modified Woodruff and Stamper assay has some important advantages compared to other adhesion assays. Erythroblasts specifically adhered to bone marrow macrophages forming clusters, as appear in vivo. Selective depletion of bone marrow macrophages by intravenous injection of dichloromethyl-enediphosphonate resulted in a release of immature erythroid cells to the peripheral blood. Furthermore no erythroblasts adhered to bone marrow sections without macrophages. Evaluating the binding of erythroblasts to bone marrow macrophages we found that this binding is temperature and cation dependent. The receptor for erythroblasts present on macrophages recognizes a sialyated protein as ligand on erythroblasts, since neuraminidase treatment of erythroblasts resulted in a decrease in binding. A possible candidate for the erythroblast receptor on macrophages is the ED2 antigen. ED2 is a differentiation antigen present on resident macrophages that has some biochemical features characteristic of an adhesion molecule. Erythroblast binding to bone marrow was inhibited using a monoclonal antibody directed against ED2.

Animals↗
PubMed1991

Bone marrow transplantation for leukemia after conditioning with busulfan and cyclophosphamide. Bone marrow morphology in the early recovery phase.

The bone marrow morphology of fifty patients with leukemia was analyzed before and two weeks after allogeneic bone marrow transplantation and compared to that of ten normal, healthy control subjects. Conditioning of the marrow graft recipients had been carried out with a combination of 16 mg/kg of Busulfan and 120 mg/kg of cyclophosphamide. The bone marrow at two weeks after transplant showed characteristic features that were unique for this clinical setting. Regenerative precursor cells with a distinct morphology commonly formed clusters or islands. Although mixed, multilinear islands were seen; the majority of islands were unilinear with a homogeneous cell content. These hematopoietic colonies were in direct proximity to degenerated cells of presumed host origin. No damage to the microenvironment was seen, the most characteristic finding being large, uniform, unilocular fat cells in close proximity to regenerative precursor cells. These morphologic changes are indicative of a complete and persistent marrow engraftment.

Adolescent↗
PubMed1989

The potential usefulness of interleukin-2 activated bone marrow cells as an active therapeutic tool against cytomegalovirus infection in a bone marrow transplantation setting.

Bone marrow transplantation (BMT) has been used in recent years for the treatment of immunodeficiency diseases, aplastic anemia, and leukemia. However, there are a number of serious problems and limitations associated with autologous or allogeneic BMT. One of these is an increase in opportunistic infections, of which cytomegalovirus (CMV) infection is one of the most important. Cytomegalovirus has been associated with more frequent deaths than any other single agent, with no reproducibly successful or therapy currently available. Recently usage of interleukin-2 or immunomodulation has been suggested as a powerful modality to combat infectious disease. In this study we showed that bone marrow activated in interleukin-2 for 2 days has the ability to lyse spleen cells infected for 3 days with murine CMV (acute infection model) or salivary gland cells infected for 7 days (chronic infection model), while nonactivated bone marrow or natural killer (NK) cells showed no such lysis. The majority of activated cells involved in lysis were antiasialo GM1-, Thy-1+/-, indicating a population of cells other than the natural killer-cell population involved.

Animals↗
PubMed1998

[Effect of the IL-6 transfected bone marrow stromal cells on the recovery of hematopoietic functions in bone marrow transplanted mice].

OBJECTIVE: To study the effect of the IL-6 transfected bone marrow stromal cell, QXMSC1 IL-6, on the hematopoietic reconstitution in bone marrow transplanted mice. METHODS: Bone marrow transplantation model was established by infusing hematopoietic cells combined with QXMSC1 IL-6 into syngeneic recipient mice through the tail vein. CFU-S, CFU-GM, CFU-E, BFU-E, and peripheral blood pictures were assayed. RESULTS: QXMSC1 IL-6 could increase the CFU-S, CFU-GM, CFU-E and BFU-E yields in BMT mice, and accelerate the recovery of peripheral blood cells. CONCLUSION: QXMSC1 IL-6 can improve the hematopoietic reconstitution in bone marrow transplanted mice.

Animals↗
PubMed2004

Excessive production of tumor necrosis factor-alpha by bone marrow T lymphocytes is essential in causing bone marrow failure in patients with aplastic anemia.

Aplastic anemia (AA) is regarded as an immunological disorder because of the clinical effect of immunosuppressive therapy. Recent studies have reported that cytokines play an important role in the development of AA. In the present study, we measured levels of T-cell derived intracellular cytokine production in peripheral blood and bone marrow (BM) of patients with AA. We demonstrated that BM lymphocytes, particularly CD4(+) and CD8(+) T cells, in patients with AA produced significantly higher amounts of tumor necrosis factor-alpha (TNF-alpha), compared with lymphocytes in normal controls. We have previously reported that expression of TNF receptor (R)1 and TNFR2 in the CD34(+) CD38(-) and CD34(+) CD38(+) fractions of patients with AA is significantly higher than those in normal control. These results indicate that BM stem cells in patients with AA may possess high sensitivity to TNF-alpha. This in turn suggests that TNF-alpha affects hematopoiesis at an earlier stage in AA patients than in normal controls. We strongly support the hypothesis that a simultaneous increase in TNF-alpha production by BM lymphocytes and sensitivity of stem cells to TNF-alpha leads to BM failure in AA.

Adult↗
PubMed2000

Bone marrow engraftment analysis after allogeneic bone marrow transplantation.

BME analysis of allo-BMT patients is used to confirm engraftment and detect MC after transplant. With frequent monitoring, the detection of MC by BME analysis may alert clinicians to a high risk of relapse and allow early intervention with a rapid taper of immunosuppression or DLI therapy. In pancytopenic patients BME analysis can help differentiate relapse from drug toxicity or infection. Although many methods have been used for BME analysis, PCR amplification of STR loci is the choice of many clinical laboratories because it is informative, quantitative, relatively rapid, and sensitive. The sensitivity of BME analysis is dependent upon many factors that need to be optimized by the laboratory performing the analysis. Although BME analysis is complex, the clinical significance for allo-BMT patients warrants the effort to develop, validate, and perform BME analysis in support of the allo-BMT service.

Bone Marrow Transplantation↗
PubMed1986

Designed transfer of specific immune responses with bone marrow transplantation.

Bone marrow transplant donors were immunized with tetanus/diphtheria toxoids 6-7 d before bone marrow donation to investigate the role of B cell subpopulations in reconstitution of humoral immunity. Lymphoblastoid B cells spontaneously producing IgG antitetanus and/or antidiphtheria toxoid were detected in the donor marrows at the time of transplantation. Recipients rapidly demonstrated 3-90-fold increases in serum IgG antitetanus and antidiphtheria toxoid levels. Antidiphtheria fragment A antibody in three donor/recipient pairs demonstrated spectrotypic identity indicating transfer of the donors' response. Reimmunization of three recipients 64-154 d after transplant revealed an IgG antibody response associated with reappearance of spontaneous antibody-producing B cells and an antidiphtheria fragment A response characteristics of the donor's immune response. These observations extend the understanding of the role of B cell subpopulations and provide a basis for specific modulation of immunity in the setting of bone marrow transplantation.

Adult↗
PubMed1994

[In vitro separation of bone marrow nuclear cells with methylcellulose and its application to autologous bone marrow transplantation in patients with leukemia].

We studied bone marrow separated with 0.05% methylcellulose and cryopreservatized with liquid nitrogen. The separation time was 43 minutes. The collection rates of nuclear cells and CFU-GM were 79.0 +/- 5.10% and 93.0 +/- 3.10% in normal marrow samples and 83.4 +/- 15.45% and 91.0 +/- 8.32% in those of acute leukemia patients. The rate of residual erythocytes was 12.5% and the bone marrow volume could be reduced by 55.2%. Application of this technique to autologous bone marrow transplantation in four patients with acute leukemia reconstituted all of their hemopoietic functions and no toxic side effect was found after transplantation.

Bone Marrow↗
PubMed2003

Constitution and telomere dynamics of bone marrow stromal cells in patients undergoing allogeneic bone marrow transplantation.

We evaluated the genotypic origin of mesenchymal stem cells (MSC) following sex-mismatched allogeneic bone marrow transplantation (BMT), and investigated the telomere dynamics in MSC in normal individuals and patients after BMT. The study population consisted of 11 patients with hematologic disorders who showed complete chimerism after BMT. Telomere length was measured in MSC using Southern blotting analysis in eight patients and 18 healthy subjects as a control group. Following culture, MSC were identified by the expression of SH2 and SH4, and lack of CD14, CD34, and CD45. All MSC showed the recipient genotype, based on the results of fluorescent in situ hybridization analysis using X-chromosome satellite probes or microsatellite DNA polymorphism analysis. The mean telomere length in MSC from normal controls was 7.2+/-0.53 kb (range, 6.12-7.78), and progressive telomere shortening was seen with age. There was no significant difference in MSC telomere length between the BMT group and age-matched controls. This study confirmed that the MSC isolated from the recipients of allogeneic BMT did not have the donor genotype, despite complete chimerism. Moreover, MSC were demonstrated to show progressive loss of telomere length with age, but the telomeres in MSC were not affected by BMT.

Adolescent↗
PubMed1992

A simple elimination of clonogenic tumor cells from human bone marrow in vitro by heat: its application to autologous bone marrow transplantation for B-cell lymphoma.

The application of hyperthermia to the treatment of neoplastic disease has focused on solid tumors. Since the hyperthermic sensitivity of human B-cell lymphoma cells is not known, we have examined the effect of hyperthermia on the growth of B-cell lymphoma cell lines (Raji and Daudi) in vitro to evaluate the ability to purge tumor cells from normal bone marrow by heat, utilizing a limiting-dilution assay to measure log depletion of tumor cells in a 20-fold excess of normal bone marrow. When exposed at 42 degrees C and 43 degrees C for 120 min, both clonogenic Raji and Daudi cells were dramatically decreased (a 4- to 6-log reduction) with exposure time, while leaving over half of the normal granulocyte-macrophage progenitor cells surviving at 42 degrees C and 10% at 43 degrees C. This high level of lymphoma-cell depletion by heat correlated with that obtained in immunologic and pharmacologic studies. These results suggest that in vitro hyperthermia might be applied effectively for the elimination of residual lymphoma cells in autologous marrow grafts before autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma.

Bone Marrow↗
PubMed1991

Radiological detection of bone and bone marrow metastases.

Bone scintigraphy is the primary method for the diagnosis of skeletal metastases. This investigation is sensitive, but the interpretation must be performed in the knowledge that it is also nonspecific. Despite this, a correct diagnosis can usually be achieved. The first-hand supplementary investigation, after a doubtful scintigraphic finding, is radiography. In most cases this is sufficient for a diagnosis. When a scintigraphic abnormality cannot be adequately explained, usually because of a negative radiographic examination, a more sensitive modality must be used. Computerized tomography offers increased sensitivity and specificity, and is primarily used for this purpose. In this way contrast resolution is increased and problems caused by obscuring tissue and complicated anatomy are reduced. Since bone metastases migrate via the active bone marrow an alternative supplementary investigation is bone marrow scintigraphy. Its usefulness is restricted by disturbing activity, from the liver and the spleen, which obscures a significant part of the active marrow, and by the fact that a lesion must be of a certain size to become apparent. Magnetic resonance imaging yields excellent images of the extension of a tumor in soft tissue. Owing to high costs and restricted availability it is still mainly used for preoperative location of metastases.

Bone Marrow↗