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PubMed1983

Histomorphologic study of bone marrow in acute leukemia following chemotherapy and autologous bone marrow transplantation.

Twenty-six patients with acute myeloid leukemia, acute lymphoid leukemia and chronic granulocytic leukemia in blast crisis were studied by means of multiple biopsies during a polychemotherapeutic or autologous bone marrow transplant protocol. Following chemotherapy, 3 main phases were observed: leukemic cellular depletion, stromal bone marrow reconstruction, and bone marrow hemopoietic restoration. Following intensive chemotherapy (in 2 patients after cyclophosphamide and total body irradiation) and autologous bone marrow transplantation, the 3 phases appeared to be shorter. A focal or diffuse increase in marrow fibrosis was a common finding in leukemia. An effective antileukemic therapy resulted in a decrease in fibrosis, whereas in some cases a further increase was a precocious sign of leukemia relapse.

Adolescent↗
PubMed1990

[Detection of bone marrow involvement in breast cancer and malignant lymphoma using immunoscintigraphy of the hematopoietic bone marrow].

Radioimmunoimaging of bone marrow was performed for non-invasive detection of skeletal involvement in 15 patients with carcinoma of the breast and 17 patients with malignant lymphomas. Bone marrow scans were performed by means of a monoclonal 99mTc-labelled antibody, directed against NCA-95 and CEA. The presence and extent of skeletal involvement were controlled by skeletal scintigraphy, plain radiographs and CT; bone marrow biopsies were obtained in 19 patients as well. 20 subjects without suspected malignant disease served as controls. Haematopoietic bone marrow was imaged homogeneously and with high contrast in all controls. 15/15 patients with carcinoma of the breast and 10/17 patients with malignant lymphomas had multifocal bone marrow defects due to skeletal metastases. Bone marrow scans revealed significantly more lesions than skeletal scintigraphy both in carcinoma of the breast (p = 0.027) and malignant lymphomas (p = 0.015). Thus, radioimmunoscintigraphy of bone marrow may provide a new, sensitive approach for non-invasive detection of metastatic spread to the skeletal system.

Adult↗
PubMed1997

The true cost of bone marrow transplantation.

Bone marrow transplantation is an example of a highly technical therapy that offers hope to patients with bone marrow failure or various malignancies. Bone marrow transplantation is much more costly "up-front" but perhaps not more costly long-term than alternative therapies. Although economic analyses appear relatively simple, interpretation and use can be problematic. Several economic analyses have identified complications that occur frequently and affect the reported cost-effectiveness of high-dose chemotherapy. Efforts to reduce the cost of bone marrow transplantation have focused on new strategies to more effectively control these complications. The introduction of new technologies to speed engraftment, to improve patient selection methods, and the shifting of care to outpatient settings all have resulted in significant reductions in duration of hospital stay, treatment-related mortality, and costs. More studies of long-term outcomes are needed for transplant and nontransplant treatment options to guide present and future applications of this treatment option.

Ambulatory Care↗
PubMed1994

[The value of bone marrow scintigraphy and magnetic resonance tomography in diagnostic imaging of bone marrow].

This article provides an overview of the possibilities and indications for magnetic resonance imaging (MRI) and bone marrow scintigraphy in imaging the bone marrow. After a brief review of the anatomical and physiologic structures of bone marrow, the principles of both methods are described. The radiopharmaceuticals of choice for bone marrow scintigraphy are the newly developed 99mTc-labelled anti-granulocyte monoclonal antibodies. They allow a high-quality, whole-body visualization of haematopetically active bone marrow by specifically targeting granulopoetic bone marrow cells and mature granulocytes. MRI enables us to visualize the bone marrow with high contrast and spatial resolution by assessing different properties of the biological tissue--mainly fat, water, and mineral content. Both methods provide a non-invasive and sensitive approach for imaging the bone marrow in different benign and malignant disorders.

Antibodies, Monoclonal↗
PubMed1999

Intermittent administration of human parathyroid Hormone(1-34) prevents immobilization-related bone loss by regulating bone marrow capacity for bone cells in ddY mice.

ddY mice, 6 weeks of age, were neurectomized (Nx) in the right hindlimbs and sham-operated (Sham) in the left limbs for evaluation of the effects of intermittent injections of human parathyroid hormone (hPTH) on trabecular bone turnover and bone marrow cell development in unloaded and loaded limbs. Mice were given subcutaneous injections of hPTH(1-34) five times a week at a dose of 0 (vehicle), 4 (low dose), or 40 (high dose) microg/kg of body weight for 2, 4, or 6 weeks. Histomorphometric analyses of the trabecular bone of the proximal tibiae revealed that high-dose hPTH injections preserved the trabecular bone volume of the Nx limbs, which was reduced after neurectomy, at the same level as that of the contralateral Sham limbs. The mineral apposition rate in the Nx limbs was elevated to values above even that of the Sham limbs by high-dose hPTH injections. The bone formation rate reduced by neurectomy was maintained at the Sham level by low- and high-dose hPTH injections. The neurectomy-induced increase in osteoclast number was suppressed by high-dose hPTH injections. In the bone marrow cells, the numbers of nonadherent and adherent cells per tibia obtained from the Nx and Sham limbs did not change. The hPTH injections decreased the numbers of nonadherent cells and increased those of adherent cells in both the Nx and the Sham limbs, but the effects were less marked in the Nx than in the Sham limbs even at high-dose injections. The formation of osteogenic nodules in the marrow cultures obtained from the Nx limbs was decreased after surgery and was maintained at the level of the Sham limbs by high-dose hPTH injections. The number of osteoclast-like multinucleated cells was reduced in the Sham limbs by high-dose hPTH injections. The value was increased at 2 weeks after neurectomy, but it was maintained at the Sham level by high-dose hPTH injections through the experimental period. The numbers of colony forming units-fibroblastic, which were reduced by neurectomy, and those of colony forming units for granulocytes and macrophages were not altered by hPTH injections. These results demonstrate that intermittent high-dose hPTH administration in the Nx limbs as well as in the contralateral Sham limbs has similar anabolic effects, stimulating osteoblast cell lineage and suppressing osteoclast cell lineage. The anabolic effects at 4 microg were reduced, but the effects at 40 microg seemed to be less affected by unloading due to sciatic neurectomy.

Animals↗
PubMed1993

Natural killer cells and bone marrow transplantation.

Bone marrow transplantation is currently used in the treatment of a variety of neoplastic and nonneoplastic diseases. However, significant obstacles still limit the efficacy of this procedure. These include the occurrence of graft-versus-host disease, the failure of the marrow to engraft, the susceptibility of patients to opportunistic infections during the period of immunodeficiency after transplantation before full recovery of immune function, and finally, the recurrence of the cancer. Natural killer (NK) cells are lymphoid cells responsible for mediating a variety of immunologic and homeostatic functions. Initially described almost 20 years ago, the full range of functions carried out by these enigmatic cells continues to unfold. NK cells may be both beneficial and deleterious in bone marrow transplantation, depending on their genotype and activation status. Resting host-derived NK cells appear capable of mediating resistance to both autologous and allogeneic bone marrow cell grafts. At the other end of the spectrum, the transfer of activated NK cells of donor type appears to produce multiple beneficial effects during both syngeneic and allogeneic bone marrow transplantation. Here, we review and attempt to reconcile the literature concerning the basic biology of NK cells and their effects on hematopoiesis, both in vitro and in vivo. We also discuss the current issues in bone marrow transplantation and the potential role NK cells may play in determining the outcome of the marrow graft, the occurrence of graft-versus-host disease, and the generation of a graft-versus-tumor response when bone marrow transplantation is used for the treatment of cancer.

Animals↗
PubMed2006

Injectable calcium phosphate scaffold and bone marrow graft for bone reconstruction in irradiated areas: an experimental study in rats.

The purpose of this study was to assess the possibilities for bone reconstruction of an injectable calcium phosphate scaffold (ICPS) associated with a bone marrow (BM) graft after irradiation in a rat model. External irradiation was delivered to 12 out of 27 inbred rats. Three weeks later, four osseous defects were created per animal and were kept empty or filled with either ICPS alone, BM graft alone or with a mixture of BM and ICPS. Three weeks after implantation, bone specimens were studied under light microscopy and by scanning electron microscopy. Filling irradiated defects with ICPS alone was not accompanied by the formation of new bone. The BM graft associated with ICPS significantly increased ceramic degradation (p<0.01) and bone ingrowth (p<0.01) in the irradiated areas. The results are evidence for the meaning of the BM in driving the bone repair in irradiated animals.

Animals↗
PubMed1989

Improved survival following HLA-incompatible bone marrow transplantation. Munich Cooperative Group of Bone Marrow Transplantation.

In most centers allogeneic bone marrow transplantation is restricted to patients with HLA-identical siblings as donors. We have transplanted 16 patients with marrow of donors other than HLA-identical siblings. Seven patients were grafted in the years 1978 until 1984. Six died of transplant complications and one of recurrent leukemia. More recently 9 patients were transplanted following an improved immunosuppressive conditioning treatment derived from experimental studies in dogs. Four are alive and in continuous remission between more than 2 months and 2 years. 5 patients died, 3 from fungal infections, one from recurrent leukaemia and one early from endothelial leakage syndrome. Our results indicate that intensified immunosuppressive conditioning may improve the results of marrow transplantation from HLA-haploidentical donors.

Adolescent↗
PubMed1993

Intraoperative bone and bone marrow sampling: a simple method for accurate measurement of uptake of radiopharmaceuticals in bone and bone marrow.

Accurate estimation of bone marrow uptake of radiopharmaceuticals is of crucial importance for accurate whole body dosimetry. In this study, a method for obtaining normal bone marrow and bone during routine surgery without inconvenience to volunteers is suggested and compared to an indirect method. In five volunteers (group 1), 4 MBq 111In-labelled human polyclonal IgG (111In-IgG) was administered 48 h before placement of a total hip prosthesis. After resection of the femoral head and neck, bone marrow was aspirated from the medullary space with a biopsy needle. In five patients, suspected of having infectious disease (group 2), bone marrow uptake was calculated according to a well-accepted method using regions of interest over the lumbar spine, 48 h after injection of 75 MBq 111In-IgG. Bone marrow uptake in group 1 (4.5 +/- 1.3% D kg-1) was significantly lower than that in group 2 (8.5 +/- 2.1% D kg-1) (P < 0.01). Blood and plasma activity did not differ significantly for both groups. This method provides a system for directly and accurately measuring uptake and retention in normal bone marrow and bone of all radiopharmaceuticals at various time points. It is a safe and simple procedure without any discomfort to the patient. Since small amounts of activity are sufficient, the radiation dose to the patient is low.

Aged↗
PubMed1993

MR imaging of bone marrow edema pattern: transient osteoporosis, transient bone marrow edema syndrome, or osteonecrosis.

The bone marrow edema (BME) pattern of signal intensity changes on magnetic resonance (MR) images (decreased on T1-weighted and increased on T2-weighted) is a nonspecific finding encountered with several entities, including transient osteoporosis of the hip, transient BME syndrome, osteonecrosis, trauma, infection, and infiltrative neoplasm. Transient osteoporosis, an unusual but distinct syndrome characterized by self-limited pain and radiographically evident osteopenia, can be distinguished from other causes of the BME pattern, particularly osteonecrosis, on the basis of clinical findings and the development of radiographically evident focal osteopenia within 8 weeks after the onset of pain. This is an important distinction, since all patients with transient osteoporosis recover completely, without intervention. The term transient BME syndrome can be used to describe any patient in whom a reversible BME pattern is seen on MR images. Although the transient BME syndrome is also self-limited and quite likely related to transient osteoporosis, the authors believe that to avoid confusion, this nonspecific term should be reserved only for patients who do not develop radiographically evident osteopenia.

Adult↗
PubMed2006

Long-term outcome of patients given transplants of mobilized blood or bone marrow: A report from the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation.

We previously compared outcomes after allogeneic peripheral-blood stem cell (PBSC) and bone marrow (BM) transplantation in 706 patients with leukemia. We obtained long-term follow up on 413 of 491 patients who were alive at the time of the initial report: 141 PBSC and 272 BM recipients. Chronic graft-versus-host disease (GVHD) was more frequent after PBSC compared to BM transplantation (RR 1.65, P < .001) yet relapse rates were similar in both groups. Leukemia-free survival rates were higher after PBSC than BM transplantation for patients with advanced chronic myeloid leukemia (33% versus 25%) but lower for those in first chronic phase (41% versus 61%) due to higher rates of late transplant-related mortality. Leukemia-free survival was similar after PBSC and BM transplantation for acute leukemia. These data represent the early experience with PBSC grafts. Long-term outcomes in recipients of more recent transplants are required to better evaluate the role of PBSC grafts relative to BM transplantation.

Bone Marrow Transplantation↗
PubMed1987

Bone marrow cells other than stem cells seed the bone marrow after rescue transfusion of fatally irradiated mice.

In a previous publication, iodinated deoxyuridine (125IUdR) incorporation data were interpreted as indicating that spleen colony-forming units (CFU-S) in DNA synthesis preferentially seeded bone marrow. In the present studies, the CFU-S content of marrow from irradiated, bone-marrow transfused mice was directly determined. Pretreatment of the transfused cells with cytocidal tritiated thymidine resulted in an insignificant diminution in CFU-S content when compared with nontritiated thymidine pretreatment, implying that there is no preferential seeding. The 125IUdR incorporation data have been reinterpreted as being a result of the proliferation of other progenitor cells present that have seeded the bone marrow.

Animals↗
PubMed2006

A European interlaboratory testing of three well-known procedures for immunocytochemical detection of epithelial cells in bone marrow. Results from analysis of normal bone marrow.

BACKGROUND: This investigation intended to study the unspecific background to be expected in normal bone marrow (BM), comparing three well recognized protocols for immunocytochemical detection of disseminated carcinoma cells. The interlaboratory variation in screening and evaluation of stained cells was analyzed and different screening methods were compared. METHODS: BM mononuclear cells (BM MNC) from 48 normal BMs were immunostained in parallel by three participating laboratories. The protocols, based on three different anti-cytokeratin antibodies, have all been in common use for detection of disseminated carcinoma cells: the A45-B/B3 protocol (Hamburg), the CK2 protocol (Augsburg) and the AE1AE3 protocol (Oslo). For all protocols, the immunostained cells were visualized by the same alkaline-phosphatase (AP) detection system (APAAP) followed by detection of the cells by manual screening and by two different automated screening systems (ACIS from Chromavision and MDS1 from Applied Imaging). Detected AP-visualized cells were morphologically classified into unambiguous hematopoietic (Uhc) and questionable cells (Qc, potentially interpreted as tumor cells). RESULTS: Seven of 48 BMs (15%) harbored > or = 1 AP-visualized cell(s) among 1 x 10(6) BM MNC, both for the A45-B/B3- and for the AE1AE3 protocol, while for CK2 a higher proportion of BMs (21 BMs; 44%) harbored AP-visualized cells (P < 0.01, McNemar's test). The number of Qc was, for all protocols, 1 log lower than the total number of AP-visualized cells. On average, the frequency of Qc was 0.04, 0.08, and 0.02 per 10(6) BM MNC with A45-B/B3, CK2 and AE1AE3, respectively, and the number of Qc-positive BMs 1, 4, and 1. The MDS1 screening sensitivity was similar to manual screening, while ACIS detected fewer cells (P < 0.001, McNemar's test). CONCLUSIONS: All protocols resulted in AP-visualization of occasional hematopoietic cells. However, morphological classification brings the specificity to a satisfactory high level. Approximately 10% of AP-visualized cells were categorized "questionable". The CK2 protocol turned out less specific than the A45-B/B3 and AE1AE3 protocols.

Adult↗
PubMed1988

Induction of transplantation tolerance by intraportal injection of allogeneic bone marrow cells. Possible implications for intrauterine bone marrow transplantation across major histocompatibility barriers.

Intraportal inoculation of C57BL/6 marrow cells into sublethally (400 rad) irradiated BALB/c recipients resulted in durable chimerism and the permanent acceptance of C57BL/6 skin allografts. Sublethally irradiated recipients of a similar number of marrow cells inoculated systemically did not develop chimerism or any significant prolongation of the survival of C57BL/6 skin allografts. Consequently, lethal graft-versus-host disease developed only in recipients of intraportal marrow allografts (80%). The intraportal injection of allogeneic C57BL/6 marrow cells into nonirradiated recipients resulted in significant, although not permanent, prolongation of skin allograft survival without durable chimerism, suggesting that the introduction of alloantigens intraportally may favor the induction of nonresponsiveness to alloantigens even across strong major histocompatibility barriers. The relevance of these findings is discussed regarding the intraportal inoculation of allogeneic bone marrow cells for the treatment of genetic disorders in utero through the induction of neonatal tolerance.

Animals↗