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PubMed2000

An overview of the Welsh bone marrow donor registry: 10 years of bone marrow donor provision.

The Welsh Bone Marrow Donor Registry (WBMDR) is in its 11th year of operation and its 4th year as an International 'Hub' participating in Bone Marrow Donors Worldwide. It is operated by the Welsh Regional Tissue Typing Laboratory which is accredited by Clinical Pathology Accreditation (UK) Ltd, and the European Federation for Immunogenetics and, together with the Welsh Blood Service, its donor centre, is ISO 9001 Registered. The active donor panel of over 21 000 regular blood donors are all HLA-A, B, DR, DQ typed (over 95% to the split specificity level or higher). All HLA-DR, DQ and over 50% of HLA-A, B typing has been performed by DNA-based methods. CMV antibody status, now tested on all donors, is known on over 70% of subjects. The WBMDR has over 80% success at obtaining Confirmatory Typing samples and operates a rapid Expanded Typing service on stored donor material. It has provided 174 bone marrow donations (140 for UK and 34 for overseas patients), and 11 lymphocyte donations, since its inception in 1989.

Adolescent↗
PubMed1994

Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation resistant to erythropoietin. Bone Marrow Transplantation Team.

A case of pure red cell aplasia after major ABO-incompatible bone marrow transplantation with long duration of up to 482 days is presented. The patient exhibited resistance to treatment using intravenous gamma globulin, prednisolone and 8 week administration of erythropoietin. The patient finally responded to treatment using erythropoietin and methylprednisolone simultaneously. Because of its safety and efficacy, it might be worthwhile to try erythropoietin with methylprednisolone, if necessary, for pure red cell aplasia complicating major ABO-incompatible bone marrow transplantation.

ABO Blood-Group System↗
PubMed1976

Human bone marrow lymphocytes. Cytotoxic effector cells in the bone marrow of normal individuals.

This study was undertaken to determine the capability of lymphocytes in the bone marrow of normal individuals to mediate nonspecific killer cell functions in assays of phytohemagglutinin (PHA)-induced cellular cytotoxicity, and antibody-dependent cellular cytotoxicity (ADCC) against 51Cr-labeled chicken erythrocyte target cells. Relatively pure mononuclear cell suspensions were obtained from bone marrow aspirates in 30 normal volunteers by sucrose gradient centrifugations and from the peripheral blood of the same individuals by Hypaque-Ficoll density centrifugations. At an effector: target ratio of 10:1, the PHA-induced cellular cytotoxicity of peripheral blood was 78.8 +/- 1.3%, while that of bone marrow was not significantly less at 66 +/- 9% (P greater than 0.1). At low effector:target ratios, the ADCC of bone marrow was negligible, while at higher effector:target ratios (20:1) bone marrow ADCC was 69 +/- 3.7%, which was comparable to that of peripheral blood. The lymphocytes themselves in the mononuclear cell suspensions of both peripheral blood and bone marrow were capable of cytotoxicity activity since depletion of monocytes from the suspensions by adherence to rayon wool and G-10 Sephadex columns did not remove the cytotoxic activity. Blocking of the Fc receptor on the effector cells by the addition of aggregated gamma globulin to the cultures suppressed the ADCC but not the PHA-induced cellular cytotoxicity of both peripheral blood and bone marrow, indicating that ADCC is dependent on an Fc receptor on the effector cell in both compartments. These studies demonstrate that the bone marrow of normal humans contains populations of lymphoid cells which have highly efficient killer cell capacities. It is uncertain what portion of these cells arise in the bone marrow and what portion enter the bone marrow parenchyma as part of the recirculating lymphocyte pool. These findings have relevance in the clearer understanding of the killer cell potential of grafted human marrow, as well as the bone marrow sequestration of functionally capable lymphocyte subpopulations in disease states and during chemotherapy.

Adult↗
PubMedDate not supplied

Bacterial contamination of bone marrow grafts intended for autologous and allogeneic bone marrow transplantation. Incidence and clinical significance.

In a series of 100 bone marrow harvests, the incidence of bacterial contamination of the bone marrow graft was 17 percent. Ex vivo manipulation of some of the grafts prior to infusion may have caused additional bacterial contamination. All isolated bacteria were common skin flora, and no serious sequelae were observed in the patients receiving the culture-positive bone marrow grafts. Samples of harvested bone marrows purposely contaminated with an isolate of Staphylococcus epidermidis demonstrated a bactericidal property that was maximal early after bone marrow collection. Bone marrow collection and ex vivo manipulation may result in considerable bacterial contamination. Procedures must be developed to assure that marrow collection and processing do not result in clinically significant contamination.

Bacteria↗
PubMed1995

Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis.

Both osteoblasts and osteoclasts are derived from progenitors that reside in the bone marrow; osteoblasts belong to the mesenchymal lineage of the marrow stroma, and osteoclasts to the hematopoietic lineage. The development of osteoclasts from their progenitors is dependent on stromal-osteoblastic cells, which are a major source of cytokines that are critical in osteoclastogenesis, such as interleukin-6 and interleukin-11. The production of interleukin-6 by stromal osteoblastic cells, as well as the responsiveness of bone marrow cells to cytokines such as interleukin-6 and interleukin-11, is regulated by sex steroids. When gonadal function is lost, the formation of osteoclasts as well as osteoblasts increases in the marrow, both changes apparently mediated by an increase in the production of interleukin-6 and perhaps by an increase in the responsiveness of bone marrow progenitor cells not only to interleukin-6 but also to other cytokines with osteoclastogenic and osteoblastogenic properties. The cellular activity of the bone marrow is also altered by the process of aging. Specifically, senescence may decrease the ability of the marrow to form osteoblast precursors. The association between the dysregulation of osteoclast or osteoblast development in the marrow and the disruption of the balance between bone resorption and bone formation, resulting in the loss of bone, leads to the following notion. Like homeostasis of other regenerating tissues, homeostasis of bone depends on the orderly replenishment of its cellular constituents. Excessive osteoclastogenesis and inadequate osteoblastogenesis are responsible for the mismatch between the formation and resorption of bone in postmenopausal and age-related osteopenia. The recognition that changes in the numbers of bone cells, rather than changes in the activity of individual cells, form the pathogenetic basis of osteoporosis is a major advance in understanding the mechanism of this disease.

Animals↗
PubMed1986

Mouse skin graft prolongation with donor-strain bone marrow and antilymphocyte serum. Effect of bone marrow cell storage.

Significant extended survival of C3H/He skin grafts in antilymphocyte serum (ALS)-treated B6AF1 mice can be brought about by the injection of donor-strain bone marrow on day 6 or 7 after grafting. In the present study, survival of the active graft-prolonging bone marrow cells under several storage conditions was investigated. The bone marrow cells retained their effectiveness if stored at 4 degrees C in 10% fetal calf serum for 18 hr prior to injection, but not if maintained at 37 degrees C under standard lymphocyte culture conditions. Freezing the cells for 10 days in a cryoprotective medium preserved the ability of the cells to prolong graft survival. In fact, freeze-thawed cells were more effective than fresh cells. Extension of the ALS-bone marrow treatment protocol to human transplantation is expected to be facilitated by frozen and short-term refrigerated storage of the donor bone marrow.

Animals↗
PubMed1993

[Immunophenotyping study of bone marrow fractions obtained by elutriation in allogeneic bone marrow transplantation].

PURPOSE: Bone marrow transplantation (BMT) is an effective treatment for acute and chronic leukaemias. Lymphocyte depletion of donor bone marrow for preventing GVHD has been associated with a higher incidence of relapse after allogeneic BMT. This association suggests an antileukaemic effect of donor lymphocytes. In vitro studies show that cytotoxic T lymphocytes (CD3+ CD56+) and NK cells (CD3-CD56+) have an antileukaemic effect. To know which specific subpopulation of lymphocytes are depleted by counterflow centrifugation or elutriation, we analysed B, T, NK cells and hematopoietic precursors in the marrow fractions after this procedure. PATIENTS AND METHODS: Eight patients (6 CML, 1 ALL, 1 B-CLL) received an allogeneic BMT with lymphocyte depletion of the bone marrow graft using elutriation. After a Percoll gradient, donor marrow mononuclear cells (MNC) were separated with this method in five fractions (F1 to F5). RESULTS: Lymphocyte depletion of donor marrow was in average of 1.7 log. This depletion was also selective, the last fraction containing higher number of cytotoxic T lymphocytes and NK cells than the other fractions. Recovery of CD34+ cells in the four fractions concerning to post-Percoll marrow was 84%, most of them being in the last fraction. CONCLUSIONS: The use of elutriation for lymphocyte depletion is a good method for graft manipulation with the feasibility to adjust a lymphocyte/Kg. dose. Elutriation may be effective in reducing the incidence and severity of graft versus host disease and preserving the antileukaemic effect.

Adult↗
PubMed1984

Busulfan-induced chronic bone marrow failure: changes in cortical bone, marrow stromal cells, and adherent cell colonies.

This study represented an effort to determine if there were quantitative or morphological changes in marrow stromal cells in busulfan-induced marrow failure and to relate these changes to other disturbances in blood and bone marrow. Mice received four busulfan (BU) injections at two-week intervals and were killed at various time points up to 40 weeks after the first injection. Evaluation techniques included complete blood counts, in vitro assay of short-term adherent cell colonies per femur (STACC per femur) and colony-forming unit-culture (CFU-C) per femur, light microscopy of sternebral marrow and spleen, and electron microscopy (EM) of sternebral marrow taken at 40 weeks. STACC per femur were acutely reduced to 25% of control, but recovered to 76% by 40 weeks. CFU-C per femur dropped to below 10% of control and never recovered. Histologically, we found that hypoplasia of acutely affected marrow was associated with heightened endosteum and cortical bone thickening. In the chronic phase of BU injury, bones became osteoporotic, and the frequency of adipocytes and mast cells rose. BU-affected spleens generally had enhanced erythropoiesis. No stromal cell changes in 40-week marrow were discernible by EM. We concluded that there were morphological changes in BU marrow stroma specifically involving endosteum, bone, adipocytes, and mast cells. Also, there was quantitative depression in stromal cells measured by the STACC assay, but this improved substantially with time, unlike damage to hematopoietic stem cells measured by the CFU-C.

Animals↗
PubMed1989

Effects of T cell depletion in radiation bone marrow chimeras. III. Characterization of allogeneic bone marrow cell populations that increase allogeneic chimerism independently of graft-vs-host disease in mixed marrow recipients.

The opposing problems of graft-vs-host disease vs failure of alloengraftment severely limit the success of allogeneic bone marrow transplantation as a therapeutic modality. We have recently used a murine bone marrow transplantation model involving reconstitution of lethally irradiated mice with mixtures of allogeneic and syngeneic marrow to demonstrate that an allogeneic bone marrow subpopulation, removed by T cell depletion with rabbit anti-mouse brain serum and complement (RAMB/C), is capable of increasing levels of allogeneic chimerism. This effect was observed in an F1 into parent genetic combination lacking the potential for graft-vs-host disease, and radiation protection studies suggested that it was not due to depletion of stem cells by RAMB/C. We have now attempted to characterize the cell population responsible for increasing allogeneic chimerism in this model. The results indicate that neither mature T cells nor NK cells are responsible for this activity. However, an assay involving mixed marrow reconstitution in an Ly-5 congenic strain combination was found to be more sensitive to small degrees of stem cell depletion than radiation protection assays using three-fold titrations of bone marrow cells. Using this assay, we were able to detect some degree of stem cell depletion by treatment with RAMB/C, but not with anti-T cell mAb. Nevertheless, if the effects of alloresistance observed in this model are considered, the degree of stem cell depletion detected by such mixing studies in insufficient to account for the effects of RAMB/C depletion on levels of allogeneic chimerism, suggesting that another cell population with this property remains to be identified.

Animals↗
PubMed1995

Successful bone marrow transplantation by bone grafts in chimeric-resistant combination.

It has been shown that the bone marrow cells (BMCs) of DBA/2 mice do not readily take in bone marrow from C57BL/6 mice, even if more than 5 x 10(6) cells are injected. In this paper, we show that such chimerism resistance can be overcome by cografting DBA/2 bones from which the hematopoietic cells have been removed but in which the stromal cells remain. C57BL/6 mice reconstituted with BMCs plus bones of DBA/2 mice survive significantly longer than C57BL/6 mice reconstituted with DBA/2 BMC alone. In the former, not only the hematolymphoid cells but also the stromal cells are replaced by donor-type cells, whereas in the latter, the donor hematolymphoid cells are rejected. These findings indicate that the stromal cells in the engrafted bones play a crucial role in the prevention of graft rejection in bone marrow transplantation.

Animals↗
PubMed1990

Bone marrow transplantation with interleukin-2-activated bone marrow followed by interleukin-2 therapy for acute myeloid leukemia in mice.

We have investigated approaches to induce graft-versus-leukemia (GVL) effect in autologous bone marrow transplantation (ABMT) without graft-versus-host disease to improve survival and cure in leukemia. The present study shows that bone marrow transplantation (BMT) using syngeneic bone marrow activated with interleukin-2 (ABM) for 24 hours in vitro, followed by interleukin-2 (IL-2) therapy, was superior to BMT with fresh, syngeneic bone marrow (FBM) in terms of survival and cure in mice with acute myeloid leukemia (P less than .001) and led to normal hematopoietic reconstitution. Addition of IL-2 therapy after BMT with FBM did not improve the results over BMT with FBM alone (P = .98). These results suggest that the GVL effect of ABMT can be enhanced by using ABM for BMT followed by IL-2 therapy without compromising engraftment.

Animals↗
PubMed2002

Bone marrow involvement in sarcoidosis: an analysis of 50 bone marrow samples.

The incidence of bone marrow involvement in sarcoidosis patients and changes in their peripheral blood parameters have been investigated. Out of 92 patients diagnosed with sarcoidosis at our center between 1994 and 2002, 50 (54.3%) gave consent for a bone marrow biopsy and were included into our study. The clinical features, peripheral blood parameters and bone marrow biopsy findings of the patients were analysed. Of these 50 patients, 39 were females and 11 were males (median age 37 years, range 16-62). Anemia was detected in 11 (22%) cases, and both anemia and leucopenia in 3 (6%). In 10% (5 patients; 3 males, 2 females) of the patients, bone marrow biopsy revealed noncaseatified granulomas. Sarcoidosis patients with bone marrow involvement had higher incidences of extrapulmonary involvement, leucopenia-lymphopenia and anemia than those without involvement (P values were 0.05, 0.001 and 0.06, respectively). Of the 11 patients with anemia, 3 had involvement of the bone marrow by sarcoidosis and 7 had iron deficiency anemia. As a result, bone marrow involvement should be considered in sarcoidosis patients with anemia, leucopenia-lymphopenia, and also extrapulmonary involvement.

Adolescent↗