Proliferation of donor spleen and bone-marrow cells in the spleens and bone marrows of unirradiated and irradiated adult mice.
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Animals↗
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[Workshop for bone marrow transplant coordinator: history of bone marrow transplant].
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Bone Marrow Transplantation↗
Bone-marrow pressure and bone strength.
The pattern of bone-marrow pressure changes differed with the mode of stress application. Intra-medullary pressure remained steady during most of the slow loading. During rapid dynamic loading, however, a slight rise in intra-medullary pressure was observed. Contraction of the femoral muscles also resulted in a greater bone-marrow pressure increase. A correlation of 0.98 (P less than 0.001) between stimulus strength and intra-medullary pressure was obtained. The rise in intra-medullary pressure with femoral muscle contraction is suggested to have a possible role under extreme stresses in living conditions.
Animals↗
[Percutaneous autogenous bone marrow grafting for repairing bone defect: an experimental study in rabbits].
OBJECTIVE: To observe osteogenesis of percutaneous autogenous bone marrow into cicatrix of bone defect. METHODS: 18 rabbits were used to observe the osteogenesis of percutaneous autogenous bone marrow into cicatrix of bone defect. A 1 cm bone defect model was made in each side of the radius. And 2 ml autogenous bone marrow was injected in the right radial bone defect after 6 weeks, and 2 ml peripheral blood in the left side. The animals were sacrificed in 1, 2, 3, 4, 12 weeks after injection. Bone formation was studied with histologic technique, X-ray examination and Ca-P quantitative estimates. RESULTS: After 1 week of injection, a big shadow of softtissue was found around the bone defect in the right side(bone marrow). Histologically a lot of new cartilage like tissues were found. In the left side(peripheral blood), no change was seen. After 4 weeks of injection, many of new bone-like shadows were observed around the defect by X-ray examination in the right side. The defect was smaller(average 1.5 mm) and bone formation was found. But in the left side, no signs for osteogenesis were noted. In 12 weeks defect was smaller(average 1 mm). Histologic sections proved well-developed bone tissue. In the left side, no bone formation found. CONCLUSION: Autogenous bone marrow can induce osteogenesis in cicatric bone defect, whereas no osteogenesis is found in the peripheral blood injection side.
Animals↗
Bone marrow necrosis.
Bone marrow necrosis is most frequently diagnosed at postmortem examination. Antemortem diagnosis is still uncommon. In a recent review of world literature, we have found 133 cases of bone marrow necrosis diagnosed during life. It has been observed during the course of a wide variety of diseases, most commonly in association with acute and chronic leukemia, carcinoma, malignant lymphoma, infections, and sickle cell disease. We report two intravitally diagnosed cases of bone marrow necrosis occurring in two patients with high-grade B-cell lymphoproliferative disease. These cases are unusual in that both patients had a triad of bone marrow necrosis, high-grade B-cell lymphoproliferative disease, and hypercalcemia. Despite chemotherapy, both cases ultimately proved fatal, with progressive involvement of the central nervous system.
Adolescent↗
Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation. University of Nebraska Medical Center Bone Marrow Transplant Group.
BACKGROUND: Diffuse alveolar hemorrhage is a frequent complication of treating malignancies with high-dose chemotherapy and bone marrow transplantation and is associated with very high mortality. This disorder's association with pulmonary inflammation, its coincidence with marrow recovery, and the usefulness of corticosteroids for treating other pulmonary hemorrhage syndromes provided the rationale for this study. METHODS: We retrospectively studied 65 episodes of diffuse alveolar hemorrhage that has occurred in 63 of 603 consecutively treated patients who had undergone high-dose chemotherapy with bone marrow transplantation. Patients were divided into three groups according to the therapy they had received for diffuse alveolar hemorrhage: supportive therapy alone (n = 12); low-dose corticosteroids (30 mg or less of methylprednisolone or its equivalent; n = 10); and high-dose corticosteroids (more than 30 mg methylprednisolone or its equivalent; n = 43). The primary outcome measures were overall survival and survival to hospital discharge, occurrence of respiratory failure requiring intubation, and development of infections subsequent to the diagnosis of diffuse alveolar hemorrhage. RESULTS: Overall survival at the end of the follow-up period was significantly higher for the high-dose corticosteroid group compared with the supportive therapy group (P = 0.005); however, treatment with low-dose steroids did not increase survival over supportive therapy alone (P = 0.198). In addition, survival to discharge was significantly increased for the high-dose group compared with the other two groups combined (33% versus 9.1%, P = 0.038). Respiratory failure after the diagnosis of diffuse alveolar hemorrhage developed in only 12 of the 22 unintubated patients in the high-dose group compared with 9 of the 10 initially unintubated patients in the other two groups (P = 0.056). Although the incidence of infections was high (40%) subsequent to diffuse alveolar hemorrhage, neither high-dose nor low-dose corticosteroid treatment significantly increased the risk of infections (P > 0.4, all comparisons). CONCLUSIONS: In this study, high-dose corticosteroid therapy for diffuse alveolar hemorrhage related to bone marrow transplantation was associated with improved total survival and survival to hospital discharge, and decreased development of respiratory failure in these patients. These results suggest the therapy is beneficial, and further prospective studies are warranted to verify the effectiveness of the treatment.
Adult↗
Surface morphology of bone marrow lymphocytes. I. Scanning electron microscopy of small lymphocytes bone marrow and spleen.
Cell separation techniques and scanning electron microscopy (SEM) were used to characterize the surface morphology of small lymphocytes in mouse bone marrow. Lymphocyte-rich fractions and unfractionated suspensions of bone marrow and spleen cells from 9--10-week-old C3H male mice were glutaraldehyde-fixed, syringed onto gelatin-coated silver membranes, dehydrated in ethanol, infiltrated with amyl acetate, critical point dried, coated with gold-palladium and examined by SEM. High proportions of cells were retained on the membranes. Purified spleen small lymphocytes showed unimodal distribution curves for cell diameter (mode, 3.4 micrometer) and for number of surface microvilli (mode, 55--60). Bone marrow small lymphocytes were identified initially in lymphocyte-rich marrow fractions and in erythroblast-depleted marrow from polycythemic mice as well as in normal whole marrow. The cells resembled spleen small lymphocytes in size distribution and they showed microvilli. However, the number of visible microvilli was lower on small lymphocytes in the bone marrow (mode, 35--40) than in the spleen. While in each small lymphocyte population the total number of microvilli was greater on larger cells than on smaller ones, the density of microvilli per unit area of cell surface tended to decrease with increasing cell size. The results establish that the small lymphocytes in mouse bone marrow, mainly locally-produced immature cells, have villous surfaces, but the number of microvilli per unit cell surface area is less than that on peripheral small lymphocytes, as seen in the spleen. Neither in the bone marrow nor in the spleen are subpopulations of small lymphocytes distinguishable solely by numbers of microvilli. The findings suggest that microvilli on bone marrow small lymphocytes may undergo further development during post-mitotic maturation, surface receptor expression and migration of the cells to peripheral lymphoid tissues.
Animals↗
Misonidazole enhances cyclophosphamide toxicity to bone marrow.
Normal bone marrow function was surveyed in animals that received cyclophosphamide after treatment with small, multiple doses of misonidazole. Peripheral blood white cell counts, cell differentials, hematocrits, bone marrow white cell counts and committed granulocyte-macrophage precursors (CFUc) were monitored for several days following treatment with misonidazole and cyclophosphamide. When results obtained from animals treated with physiological saline or misonidazole in advance of cyclophosphamide were compared, no significant differences were noted in routine assays of white blood cell count, cell morphology or hematocrit. Pre-treatment with misonidazole, however, caused a significant reduction in survival and delay in recovery of bone marrow CFUc (p less than .01). The combined use of misonidazole and cyclophosphamide also reduced animal survival (DMF = 1.2), with the majority of deaths being attributable to failure of normal hematopoietic function. These results suggest that misonidazole enhances the myelotoxicity associated with cyclophosphamide use. This additional damage is not detectable using routine hematological assays, but is demonstrable in assays of bone marrow stem cells and animal survival studies.
Animals↗
Depletion of T cells from bone marrow for allogeneic transplantation: method for treatment of bone marrow in bulk.
T lymphocytes were depleted from donor marrow for 23 patients undergoing allogeneic bone marrow transplantation using an anti-T-cell antibody, CT-2, and complement. The methodology is described in detail for in vitro depletion of large quantities of bone marrow. The extent of T-lymphocyte depletion using various T-cell markers, the percent of marrow lost in the processing and quantity of antibody, and complement needed are presented. These techniques for in vitro T-lymphocyte depletion were reproducible and did result in an average final yield of 47% of the harvested donor marrow.
Antibodies, Monoclonal↗
Percutaneous treatment of long bone nonunions: the use of autologous bone marrow and allograft bone matrix.
Sixty-six patients with 69 "stiff" nonunions (no gross motion) of long bones were entered into a prospective study. The only therapeutic intervention was the percutaneous administration of a mixture of autologous bone marrow and allograft demineralized bone matrix on an outpatient basis. Sixty-one of the percutaneous treatments (88%) resulted in union at an average of 8.1 months (range: 2 months to 3 years). This method of treating nonunions is as successful as standard iliac crest autologous bone grafting and offers the distinct advantages of decreased morbidity, reduced costs, and shorter hospital stay.
Adolescent↗
Both bone marrow- and non-bone marrow-associated factors determine susceptibility to experimental autoimmune encephalomyelitis of BUF and WAG rats.
To determine the feasibility of treatment with allogeneic bone marrow for experimental autoimmune encephalomyelitis, we investigated the susceptibility to experimental autoimmune encephalomyelitis of bone marrow chimeras using BUF, (WAG X BUF)F1 (high responder), and WAG (low responder) rats. In contrast to previous studies in which other rat strains were used, the response was largely determined by the genotype of the grafted bone marrow, but the influence of a non-bone marrow-associated factor was evident. The latter factor was identified as a low corticosterone response in BUF rats and a high corticosterone response in WAG rats. After adrenalectomy, a significant proportion of WAG rats developed clinical experimental autoimmune encephalomyelitis. The bone marrow-associated factor of resistance appeared to be the activity of cyclophosphamide-sensitive suppressor cells. The latter cells were found to interfere with the formation of inflammatory foci in the central nervous system, while corticosterone primarily prevents the clinical expression of lesions.
Animals↗
[ Magnetic resonance imaging in the early diagnosis of bone marrow necrosis].
Bone marrow necrosis (BMN) is a rare entity characterised by fever and bone pain, accompanied by hypercalcemia and increased LDH. Amorphous eosinophilic material is present in the bone marrow aspirate, with isolated cells in different degrees of necrobiosis. These are frequently post-mortem findings, appearing in up to 19.8% of all autopsies, mostly after haematological malignancies with proliferative features (acute leukaemia, lymphoma). In general terms, BMN is regarded as a poor prognosis sign. Bone gammography with Tc has been included among the diagnostic procedures, in an attempt to carry out an early detection of BMN and to determine its spread. Magnetic resonance imaging (MRI) has recently been regarded useful to evaluate bone marrow involvement in this condition. A 53 year-old woman is presented here who, two and a half years after being diagnosed of mantle cell lymphoma, and having a relapse on her neck lymph nodes, presented severe bone pain showing no radiological evidence of osseous involvement. MRI showed ample spongy marrow involvement of her lower spine, sacrum and pelvic bones. Both femoral heads were preserved, hypointense images being observed in T1, whereas subcortical, hyperintense ones appeared in T2. Bone marrow aspirate showed poor cellularity, with different degrees of necrobiosis on a stippled background. The picture was interpreted as BMN secondary to non-Hodgkin's lymphoma.
Bone Marrow↗
IL2 activated killer cells may contribute to cytomegalovirus induced marrow hypoplasia after bone marrow transplantation.
Cytomegalovirus (CMV) infection remains the commonest cause of infective death following allogeneic bone marrow transplantation (BMT). CMV disease post-BMT occurs in the context of compromised cellular defence mechanisms and is associated with marrow hypoplasia and pneumonitis. However, CMV infection induces release of interleukin 2 (IL2) which in turn generates MHC unrestricted lymphokine activated killer (LAK) cells. We have investigated whether recruitment of IL2 activated MHC unrestricted defence mechanisms post-transplant can be implicated in the marrow hypoplasia that frequently accompanies CMV infection. The results show that IL2 activated peripheral blood mononuclear cells (PBMC) have substantial cytotoxicity against MHC matched and MHC mismatched marrow fibroblasts but that this activity is not specific for CMV infected fibroblasts; uninfected target cells are also equally killed. Furthermore, post-BMT PBMC show greater responsiveness to IL2 than normal PBMC in killing of marrow fibroblasts. We provide a hypothesis from these observations which may explain some of the consequences of CMV infection post-BMT. Local production of IL2 activated cytotoxic cells which would be generated during CMV infection would damage uninfected as well as infected marrow fibroblasts and thereby could compromise haemopoietic growth factor production by marrow fibroblasts. Similarly generated cytotoxicity in the lung may accompany CMV pneumonitis. Our results suggest that administration of anti-IL2 receptor antibody may have a therapeutic role in CMV disease post-BMT as has recently been shown in graft-versus-host disease.
Adolescent↗
Niemann-Pick disease type C (a cellular cholesterol lipidosis) treated by bone marrow transplantation.
Bone marrow transplantation (BMT) has been used for a wide variety of lysosomal storage diseases with encouraging results. We report a 3-year 5-month-old girl with Niemann-Pick type C disease (NPC) who received an allogeneic BMT. The patient presented with repeated lower respiratory tract infections, hepatosplenomegaly, failure to thrive, and developmental delay. Chest computed tomography (CT) revealed diffuse interstitial lung infiltration. Bone marrow and liver biopsies revealed abundant lipid-filled foamy macrophages. Skin fibroblast sphingomyelinase assay revealed partial deficiency. The ability of her skin fibroblasts to esterify cholesterol was very low, and the cells stained brightly for free cholesterol. She received BMT from a healthy HLA-identical male sibling donor at the age of 2 year 6 months. Full engraftment was evidenced by repeated bone marrow sex chromosome studies. Regression of the hepatosplenomegaly, markedly reduced foamy macrophage infiltration in bone marrow, and decreased interstitial lung infiltration was noted 6 months after BMT. Her neurological status, however, deteriorated. Follow-up magnetic resonance image (MRI) revealed progressive, diffuse brain atrophy. We conclude that resolution occurred in the liver, spleen, bone marrow and lung following successful engraftment. Such a response is remarkable since the underlying problem involves a membrane receptor for cholesterol. This positive response might be due to replacement of the monocyte-phagocytic system or it may imply the existence of cross-correction in the NPC membrane receptor defect by BMT approach. Since BMT did not halt the neurological deterioration, it is unlikely to be an adequate treatment for NPC.
Bone Marrow Transplantation↗
Bone marrow histology in myelodysplastic syndromes. I. Histological findings in myelodysplastic syndromes and comparison with bone marrow smears.
Forty bone-marrow trephine biopsies of patients with myelodysplastic syndromes (MDS) were studied and compared with bone marrow smears. It proved possible to make the diagnosis of MDS on the basis of bone-marrow biopsies. Features of abnormal erythropoiesis and myelopoiesis, although different from those observed in smears, were easily detectable. Moreover, obvious advantages of bone-marrow biopsy over bone-marrow smears were found. Firstly, the biopsy in MDS gives an exact assessment of the cellularity; secondly, the presence of reticulin fibres, increased in the majority of the cases, can be evaluated; thirdly, dysmegakaryopoiesis is more easily detected in trephine biopsies than in smears; finally, abnormal behaviour of myeloblasts, clustering centrally in the bone marrow, is frequently observed before the smears show an excess of myeloblasts. The bone-marrow biopsy also has a role in difficult cases, where the diagnosis of MDS can not be established on just bone-marrow smears. The five types of MDS, as described by the FAB group, do not represent recognizable histological entities.
Adult↗
Regulation of B cell development in mouse bone marrow.
Cultured bone marrow cells, after in vitro treatment with hydroxyurea (HU) - a DNA synthesis inhibitor which kills cells in the S phase of the cell cycle - generated 40 to 70% more B cells than untreated control cells. This was shown by fluorescent-activated cell sorter analysis of labelled cells using FITC-F(ab')2 rabbit anti-mouse IgM and functional tests with LPS. The maximum increase was reached after 24 hr of incubation with HU while 6 or 2 hr of exposure had less effect. The effect of HU was dose dependent with a maximum at 4 mM. The same increase of B cells was observed with foetal liver cells but not with spleen or lymph node cells after 24 hr of in vitro HU treatment. Dialysed supernatants from HU treated bone marrow, spleen or foetal liver cells were themselves able to augment the B cell maturation in bone marrow cultures (test cells) as compared with supernatants from untreated cells, showing that soluble factors were involved. Preliminary data showed that inhibitory factors for B cell maturation were produced by normal bone marrow, spleen and thymus cells in vitro and their formation was prevented by HU pretreatment or irradiation (2500 R) whereas stimulatory factors were produced by lymph node cells. Cell separation experiments suggested that T cells and/or adherent cells may be involved in the production of these soluble factors. These data suggest that early B cell development may be under homeostatic control.
Animals↗
[Restorative processes in the bone marrow of irradiated rats after homologous bone marrow therapy].
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Animals↗
[Reversal of myelofibrosis is an important pre-transplant factor for bone marrow grafting--a successful case of allogeneic bone marrow transplantation for an acute megakaryoblastic leukemia].
We report a successful ereated case of acute megakaryoblastic leukemia (AMKL) with myelofibrosis (MF), which achieved a disease free condition, with disappearance of MF, for over 24 months after allogeneic bone marrow transplantation (BMT) and summarized cases of MF receiving BMT reported in Japan to evaluate the influence of MF on engraftment of bone marrow (BM). A 40-year-old man was admitted on Jan. 29, 1991 due to anemia and thrombocytopenia. BM aspiration resulted in a dry tap and MF and cells stained positive with anti-GPIIb/IIIa (CD41a) antibody were demonstrated by BM the biopsy specimen. Complete remission was achieved by multi-drug chemotherapy including behenoylcytosine arabinoside, etoposide, mitoxantrone and prednisolone (PLS). After preconditioning with little BU+CY, BMT was performed from an HLA-identical brother on Jan. 16, 1992. From day 9 of post BMT, acute skin graft versus host disease (grade 1) was observed, which was controlled by 60 mg/day of PSL. Engraftment was achieved on day 12. Although cystitis developed, he was discharged on Apr. 5, 1992 and remains disease free. Including the present case, seven allogeneic BMT patient with MF have been reported so far in Japan. Four cases in whom MF recovered before BMT showed better results than other three cases that still showed MF at BMT. Reversal of MF seems to be a favorable pre-transplant factor for successful BMT in patients with MF.
Adult↗