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PubMed2000

Suppressor activity of bone marrow cells and localization of fluorescent-labeled bone marrow cells within ovine endometrial tissue.

Numbers of fluorescein isothiocyanate (FITC)-labeled bone marrow (BM) cells of donor lambs were quantified within endometrial cell suspensions following their administration to ovariectomized (OVX; control-and estradiol-17beta-treated) and intact (estrus, d-14 cyclic and pregnant) ewes. The numbers of fluorescent BM cells were greater (P < .05) for the estrous and d-14 cyclic ewes than for both groups of OVX ewes. Fractionation of the endometrial cells with Percoll revealed that the majority of fluorescent cells were low-density (1.002 to 1.056 g/mL) cells. In coculture experiments, low-density cells from lamb BM not only suppressed the incorporation of thymidine into phytohemagglutinin-treated peripheral blood lymphocytes, but the cells also released suppressor factor into the culture medium. Suppressor activity tended to be reversed (P < .1) by a pan-specific neutralization antibody to transforming growth factor-beta (TGF-beta); however, the activity was unaffected by a neutralization antibody to TGF-beta2. These findings suggest that ovine endometrial suppressor cells may represent a population of low-density BM-derived natural suppressor cells, and their trafficking and localization patterns may depend on an ovarian factor(s). Further, suppressor activity does not seem to be mediated by TGF-beta2.

Animals↗
PubMed1998

Suppression of graft-versus-host disease and amplification of graft-versus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation.

Bone marrow transplantation (BMT) is currently used for the treatment of a variety of neoplastic diseases. However, significant obstacles limiting the efficacy of allogeneic BMT are the occurrence of graft-versus-host disease (GvHD) and tumor relapse. Natural killer (NK) cells exert a variety of immunologic and homoeostatic functions. We examined whether adoptive transfer of activated NK cells of donor type would prevent GvHD after allogeneic BMT in mice. Lethally irradiated C57BL/6 (H-2(b)) mice, were transplanted with MHC incompatible BALB/c (H-2(d)) bone marrow cells and spleen cells and rapidly succumbed to acute GvHD. In contrast, mice that also received activated NK cells of donor type exhibited significant increases in survival. In determining the mechanism by which the NK cells prevented GvHD, mice were concurrently treated with a neutralizing antibodies to the immunosuppressive cytokine TGFbeta. Anti-TGFbeta completely abrogated the protective effects of the activated donor NK cells indicating that TGFbeta plays an important role in the prevention of GvHD by NK cells. We then examined whether activated NK cells of donor type after allogeneic BMT would induce graft-versus-tumor (GvT) effects without GvHD in mice bearing a murine colon adenocarcinoma (MCA-38). 10 d after receiving the tumor, in which the mice had demonstrable lung metastases, recipients received an allogeneic BMT with or without activated NK cells. Administration of activated NK cells resulted in significant GvT effects after allogeneic BMT as evidenced by increases in median survival and fewer lung metastasis. No evidence of GVHD was detected compared with recipients receiving spleen cells alone which also developed fewer lung metastases but in which all had succumbed to GVHD. Thus, our findings suggest that adoptive immunotherapy using activated donor NK cells combined with allogeneic BMT inhibits GvHD and promotes GvT in advanced tumor-bearing mice. These results also suggest that GvT and GvHD can be dissociable phenomena.

Adenocarcinoma↗
PubMed1988

Recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) after bone marrow transplantation.

Bone marrow transplantation improves the chances of survival in a variety of hematological malignancies. However, infectious complications during the post-transplant phase contribute significantly to morbidity and mortality. To reduce the duration of granulocytopenia, which is approximately 20 days after BMT, in this study patients with ALL, relapsed or high-grade NHL, relapsed or refractory HD, or Neuroblastoma stage III/IV, were given rh GM-CSF to assess the effects on hematological and immunological reconstitution after conditioning therapy and BMT. The results of 9 patients are presented. After autologous BMT and subsequent rh GM-CSF therapy, a peripheral blood neutrophil count of 500/microliters was reached within 8-12 days, i.e., between 7 and 10 days earlier than would have been expected without rh GM-CSF. Furthermore, it appeared that rh GM-CSF was useful in case of insufficient bone marrow regeneration post autologous transplant. The influence of rh GM-CSF after allogeneic BMT is not yet clear. Further studies will be necessary to evaluate the potential of this promising new drug after BMT.

Adult↗
PubMed1993

The value of HLA-ABC common typing tray in relation to bone marrow transplantation.

Bone marrow transplantation (BMT) is one of the most effective procedures to cure the previously uncured hematologic diseases. However, it is costly and HLA typing to select the compatible donors contributed to its cost. A total of 53 prospective patients for BMT and their 114 siblings were analyzed to evaluate the use of locally prepared HLA-ABC common typing tray (ABCCT) during Mar 1988-Mar 1992. The 16, 9, 7, 5, 5 and 12 patients were diagnosed as aplastic anemia, CML, thalassemia, ALL, ANLL and other blood diseases, respectively. It was found that 18 patients were HLA-identical (HLA-ID) with one of their siblings except one patient had 2 HLA-ID sibs. All of those who appeared to be HLA-ID were further tested for the HLA-ABCDR typings. It was observed that 16 (88.89%) of 18 patients and 17 (89.47%) of 19 sibs were confirmed as HLA-ID. After careful clinical screening, only 13 HLA-ID pairs were able to proceed to the mixed lymphocyte culture and confirmed their status of HLA-ID by this test. Finally, only 6 (46.15%) of 13 patients received BMT with a high rate of success, ie all patients have survived with bone marrow engraftment. Thus, ABCCT is very useful for related BMT. It was highly efficient to exclude HLA-non-ID and haplo-ID yet the cost and workload were greatly reduced.

Bone Marrow Transplantation↗
PubMed1992

Osteogenesis associated with bone gla protein gene expression in diffusion chambers by bone marrow cells with demineralized bone matrix.

Diffusion chambers with rat bone marrow cells and demineralized bone matrix (DBM) were implanted subcutaneously to syngeneic 8-week-old rats and were harvested every week 3-7 weeks after implantation, and histochemical examination, determination of alkaline phosphatase activity, total calcium and phosphorus, the bone-specific vitamin K-dependent gla-containing protein (BGP) content, and detection of BGP mRNA relative to mineralization were performed. Alkaline phosphatase in diffusion chamber implants reached the highest activity at 4 weeks and then decreased. Calcium and phosphorus deposits occurred at 4 weeks after implantation and were followed by marked increases until 7 weeks, which was comparable to the accumulation of BGP. The BGP gene within the diffusion chambers began to be expressed at 5 weeks, and its expression increased markedly at 7 weeks after implantation. At 4-5 weeks after implantation, new bone adjacent to the membrane filters and cartilage toward the center of the diffusion chamber were observed histochemically. Light microscopic and immunohistologic examinations of chambers with marrow cells and DBM revealed production of mineralized matrices, typical of bone characterized by the appearance of BGP and mineralized nodules. In contrast, bone marrow cells alone did not show extensive bone formation and yielded very low values for these biochemical parameters. The present experiments demonstrate the potential of bone marrow cells and DBM to produce not only cartilage formation but also membranous bone formation associated with increasing expression of BGP mRNA during the later stages of bone formation, as well as a marked accumulation of BGP.

Alkaline Phosphatase↗
PubMed1989

Comparison of human long-term bone marrow cultures (HLTBMCs) established from fresh and post-cryopreservation bone marrow samples from living and cadaver donors.

Human long-term bone marrow cultures (HLTBMCs) were established from thawed post-cryopreservation, as well as from cadaver donor bone marrow (BM) samples. The longevity was similar in the different series of HLTBMCs examined. CFU-GM could be cultured out of cadaver donor BM. This indicates that previously healthy people, under the conditions generally accepted as suitable for organ donation, could become suitable donors for allogeneic BM transplantation.

Bone Marrow Cells↗
PubMed1979

Bone marrow metastases without cortical bone involvement in breast cancer patients.

Bone marrow involvement by breast carcinoma in the absence of demonstrable bone lesions is unusual. We report six patients with medullary tumor without demonstration of cortical bone abnormality on scan or radiographs. This represents 2.8% of 213 patients with breast cancer in which bone marrow examination was performed and 6.2% of those in which marrow involvement was demonstrated.

Adenocarcinoma↗
PubMed1978

Differentiation between benign and malignant monoclonal gammopathies by discriminant analysis on serum and bone marrow parameters.

Bone marrow samples of 28 individuals with clinically benign and of 41 patients with malignant monoclonal gammopathy were analyzed for the total number of lymphoplasmocellular elements containing cytoplasmic immunoglobulins and for the monoclonal fraction of these cells. Monoclonal immunoglobulin components were determined in sera. A discriminant analysis was performed on the data: the variables were transformed and in a stepwise procedure used for the construction of a discriminant function which by adividing point allowed a good distinction between the two groups of patients. By use of this discriminant function, 91% of the patients in the sample were correctly classified.

Adult↗
PubMed1988

Cytomegalovirus infection after autologous bone marrow transplantation with comparison to infection after allogeneic bone marrow transplantation.

Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P = .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P = .02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P less than .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v 23%, P less than .001).

Bone Marrow Transplantation↗
PubMed1996

Stromal abnormalities in neoplastic bone marrow diseases.

Bone marrow malignancies are clonal disorders resulting from neoplastic transformation of hematopoietic stem or progenitor cells. Similar to their normal counterparts, transformed blood-forming cells remain dependent on signals from the hematopoiesis-regulating stromal environment for survival and proliferation. There is increasing evidence that the microenvironment may also take a more active part in the disease process. A review of the literature on stromal abnormalities in the leukemias, the myelodysplastic syndromes, and multiple myeloma reveals three principal mechanisms by which stromal derangements can contribute to the evolution of a neoplastic disease. In the simplest case, neoplastic blood-forming cells induce reversible changes in stroma function or composition which result in improved growth conditions for the malignant cells ('malignancy-induced microenvironment'). In the second setting, functionally abnormal end cells derived from the malignant clone become an integral part of the stroma system, selectively stimulating the neoplastic cells and inhibiting normal blood cell formation ('malignant microenvironment'). In the third condition, the emergence of a neoplastic cell population is the consequence of a primary stroma lesion characterized by inability to control regular blood cell formation ('malignancy-inducing microenvironment'). The perception of different stroma-related disease mechanisms may eventually lead to the development of alternative therapeutic approaches.

Acute Disease↗
PubMed1992

The meaning of quality of life for bone marrow transplant survivors. Part 2. Improving quality of life for bone marrow transplant survivors.

Surviving bone marrow transplant (BMT) represents a major victory against malignant disease but also creates challenges of survivorship for patients and the professionals who care for them. Part 2 of this report presents the findings of a qualitative study (N = 119) related to improving quality of life (QOL) for BMT survivors. Results are shared based on BMT survivors' perceptions of (a) what makes QOL better, (b) what makes QOL worse, and (c) what doctors or nurses could do to enhance QOL. The findings of the study have been useful in constructing a quantitative instrument to measure QOL in BMT and in understanding the conceptual basis of QOL for the BMT population. Nursing interventions can improve the QOL for the BMT patient across all phases of the transplant process and long-term issues related to survival.

Bone Marrow Transplantation↗
PubMed1989

Prognostic value of bone marrow biopsy in chronic lymphoid leukemia. A study of 98 initial bone marrow biopsies.

This study deals with bone marrow biopsies (MB) performed at the initial assessment of our 98 patients included in the French LLC 80 and LLC 85 trials. The prognostic value of the type of medullary invasion was confirmed, with a 6-year survival rate of 44% for the diffuse type (D = 42 patients) as against 68.4% for the non-diffuse type (ND = 56 patients) (p = 0.01). However, comparison of these 2 groups showed a significant difference for 19 of the 25 parameters studied, the differences always being to the prognostic disadvantage of the diffuse group. Bone marrow involvement (BMI) was very closely correlated with the ABC staging system (p less than 0.001). Despite more frequent disease progression among the cases of diffuse BMI, the survival rates in stage A patients were similar: 73.9% for 48 ND patients as against 59.6% for 19 D patients (p greater than 0.50). The ABC system of classification seems more discriminating than that recently proposed by Rozman specially for identifying the favorable groups.

Aged↗
PubMed1990

The CD24 antigen discriminates between pre-B and B cells in human bone marrow.

When bone marrow (BM) lymphoid cells from 12 adult healthy donors were labeled by CD24 antibodies and analyzed by flow cytometry, two positive populations of cells were demonstrated in each sample (by a separated bimodal specific immunofluorescence). One population had intermediate CD24-Ag density (termed CD24+ cells) whereas the other had high CD24-Ag density (termed CD24(2+) cells). CD24+ cells represented 5.8 +/- 2.7% of the total lymphoid BM cells and CD24(2+) cells 5.6 +/- 2.5%. Using dual fluorescence analysis on eight samples, all CD24+ cells expressed the CD21 and CD37 mature B cell Ag and also surface IgM (sIgM), but this population lacked CD10 Ag. These cells also expressed CD19 Ag, and at a higher density than CD24(2+) cells. They were also positive for HLA-DR Ag. Conversely, CD24(2+) cells were shown to be early cells of the B cell lineage. While all the CD24(2+) cells were HLA-DR+ and CD19+, 64 +/- 16% of them expressed CD20 Ag (at a lower density than CD24+ cells), 65 +/- 21% CD10 Ag, and 22 +/- 8% were positive for cytoplasmic mu-chains (c mu). None of these cells expressed the CD21 and CD37 mature B cell Ag or sIgM. Additional experiments on four different healthy donors demonstrated that 30 +/- 9% of the CD24(2+) cells expressed the CD34 Ag and that the CD24+ cells did not express it. Thus, the CD24 Ag permits discrimination between two populations of the B cell lineage present in adult BM: 1) A CD24(2+) cell population including "pre" pre-B cells (HLA-DR+, CD19+, CD10+/-, CD20-, CD21-, CD34+, CD37-, c mu-), "intermediate" pre-B cells (HLA-DR+, CD19+, CD10+, CD20+, CD21-, CD34-, CD37-, c mu-), and "true" pre-B cells (HLA-DR+, CD19+, CD10+, CD20+, CD21-, CD34-, CD37-, c mu+). 2) A CD24+ cell population including B cells of the standard phenotype (HLA-DR+, CD19+, CD10-, CD20+, CD21+, CD34-, CD37+, c mu-, sIgM+).

Adult↗
PubMed2002

Prevention of senile osteoporosis in SAMP6 mice by intrabone marrow injection of allogeneic bone marrow cells.

The SAMP6 mouse (a substrain of senescence-accelerated mice) spontaneously develops osteoporosis early in life and is, therefore, a useful model for examining the mechanisms underlying osteoporosis. We have recently established a new bone marrow transplantation (BMT) method: the bone marrow cells (BMCs) of normal allogeneic mice are directly injected into the bone marrow (BM) cavity of irradiated (5.5 Gy x 2) recipients (IBM-BMT). Using IBM-BMT, we attempted to prevent osteoporosis in SAMP6 mice. The hematolymphoid system was completely reconstituted with donor-type cells after IBM-BMT. Thus-treated SAMP6 mice showed marked increases in trabecular bones even at 12 months of age, and the bone mineral density remained similar to that of normal B6 mice. In concordance with these findings, urinary deoxypyridinoline also remained continuously low until 10 months of age, indicating that IBM-BMT was effective in the prevention of bone absorption. In addition to the above, BM stromal cells in the treated SAMP6 mice were replaced with donor stromal cells, and the message level of interleukin-11 (IL-11), which is produced by the BM stromal cells and is known as an important factor in the regulation of bone remodeling, was restored to a level similar to that observed in normal B6 mice. Furthermore, the message level of IL-6, which is known to enhance osteoclastogenesis, was also restored to normal. These results indicate that the BM microenvironment was normalized after IBM-BMT and that the increased production of IL-11 and IL-6 ameliorated the imbalance between bone absorption and formation, resulting in the prevention of osteoporosis in SAMP6 mice.

Amino Acids↗