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PubMed1994

Bone marrow aspirate immunofluorescent and bone marrow biopsy immunoperoxidase staining of plasma cells in histologically occult plasma cell proliferative marrow disorders.

Immunofluorescent staining (immunofluorescence bone marrow aspirate) and immunoperoxidase staining (immunoperoxidase bone marrow biopsy) were compared in 26 patients with plasma cell dyscrasia and less than 10% marrow plasma cells. Their clinical diagnoses included monoclonal gammopathy of undetermined significance (13 patients), treated multiple myeloma (four patients), multiple myeloma with less than 10% marrow plasma cells (two patients), primary systemic amyloidosis (two patients), monoclonal gammopathy of undetermined significance with neuropathy (two patients), angiofollicular lymph node hyperplasia (two patients, all with the POEMS [polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes] syndrome), and primary (amyloidosis) amyloid neuropathy (one patient). The percentage of plasma cells was greater than 5% in 23% of patients and less than or equal to 5% in 77% of patients. With immunofluorescence bone marrow aspirate and immunoperoxidase bone marrow biopsy, light-chain restriction was demonstrated in 84% of all cases and accurately determined in 96% of all cases as shown by serum and urine paraprotein analysis or tissue amyloid typing. Monoclonal populations of plasma cells can be readily identified with immunofluorescence bone marrow aspirate and immunoperoxidase bone marrow biopsy in most patients with paraproteins and marrow plasmacytoses not diagnostic of multiple myeloma.

Adult↗
PubMed1991

[A histopathological study of bone marrow in acute myeloid leukemia. Bone marrow biopsy changes before chemotherapy and comparison with bone marrow smears].

Histopathological changes of pretreatment bone marrow biopsy from 42 cases with acute myeloid leukemia (AML) were described. A considerable difference was shown between the results of aspirate smears and the findings of plastic embedded biopsy sections, particularly in bone marrow cellularity such as infiltration of inflammatory cells and presence of residual hemopoietic cells, qualitative and quantitative abnormalities of megakaryocytes suggestive of myelodysplastic features were more accurately assessed in the sections of marrow biopsy than in the aspirate smears. In three cases there was considerable infiltration of maturing but dysplastic granulocytic cells and erythroid precursors in the sections, but not in the aspirate smears. Our study shows that plastic embedded biopsy sections provide more information than aspiration smears for the diagnosis of AML.

Adolescent↗
PubMed1986

Philadelphia-positive metaphases in the marrow after bone marrow transplantation for chronic granulocytic leukemia.

A 28-year-old man with Ph-positive chronic granulocytic leukemia (CGL) was treated by high-dose chemoradiotherapy and transplantation of marrow cells harvested from his HLA-identical brother. One year after bone marrow transplantation (BMT) examination of his marrow showed a minority population of Ph-positive cells; their proportion subsequently fell such that 2 years after transplant analysis of marrow cells showed only cytogenetically normal cells. The patient remains clinically normal with a persisting mild lymphocytosis but without hematological evidence of leukemia. We cannot in this patient distinguish between persisting leukemia that later could no longer be recognized and relapse of leukemia that is now suppressed, perhaps only temporarily. This case emphasizes the need for caution in interpreting chromosomal finding after BMT for CGL.

Adult↗
PubMed1988

Transfusion of bone marrow red cells during bone marrow harvests.

Large volumes of bone marrow may be required for certain types of autologous bone marrow transplants. The present study was done to determine whether red cells obtained during a bone marrow harvest would be useful in reducing homologous transfusion requirements. A group of patients receiving standard transfusion support during the harvest (group 1) was compared to a group that received processed bone marrow red cells (PBMRBC) (group 2). Using the Cobe 2991 cell processor, 90% of the harvested bone marrow red cells were extracted and transfused during the procedure. Group 2 received a median of 1500 ml of blood processed from the bone marrow or 413 ml (volume of marrow processed x hematocrit) of red cells. Infusion of the PBMRBC reduced the homologous transfusion requirement from 6.5 units to 3.0 units (p = 0.02). In addition, group 1 had a 20% decrease in hematocrit following transfusion compared to the pre-harvest hematocrit, as opposed to an 8% decrease in group 2 (p = 0.02). This study indicates that PBMRBC can reduce the homologous transfusion requirements during an autologous bone marrow harvest.

Adolescent↗
PubMed1993

Increased interleukin-6 production by murine bone marrow and bone cells after estrogen withdrawal.

We have previously shown that cytokine-induced production of interleukin-6 (IL-6) by cultured bone marrow-derived stromal and osteoblastic cells is inhibited by 17 beta-estradiol, and that estrogen withdrawal (ovariectomy) in mice causes an up-regulation of osteoclast development which can be prevented by a neutralizing antibody against IL-6 or estrogen replacement. To directly establish the link between estrogen loss and altered IL-6 production, implied by our earlier studies, we have now compared IL-6 production in ex vivo cultures of bone marrow cells from mice that were sham operated, ovariectomized, or ovariectomized and treated with 17 beta-estradiol. In addition, we have examined the effect of the in vitro withdrawal of estrogens from primary cell cultures of neonatal murine calvaria on IL-6 production. IL-6 production in ex vivo cultures of bone marrow cells maintained in the presence of 1,25-dihydroxyvitamin D3 or PTH was greater in marrow cells from ovariectomized mice than in those from sham-operated animals or ovariectomized animals receiving estrogen replacement. In line with this finding, addition of 17 beta-estradiol to calvaria cell cultures followed by withdrawal of the steroid caused an increase in the amount of IL-6 produced in response to the subsequent stimulation of these cultures with IL-1 or PTH compared to that in cultures that had never been treated with estradiol; when the inactive isomer 17 alpha-estradiol was used, no change in IL-6 production was observed. These results establish that estrogen loss causes an up-regulation of IL-6 production by bone marrow cells and that a similar phenomenon can be elicited in vitro by withdrawal of 17 beta-estradiol from primary cultures of bone cells.

Animals↗
PubMed1983

Pre-B-cells in normal human bone marrow and in bone marrow from patients with leukemia in remission: persistent quantitative differences and possible expression of cell surface IgM in vitro.

Pre-B-cells are bone marrow lymphoid cells that lack surface immunoglobulin (sIg-) but contain intracytoplasmic (c) IgM heavy chains and are probably the immediate precursors of immature sIgM+ B lymphocytes. To better understand early stages of B-cell development, immunofluorescence techniques were employed to identify pre-B-cells and B lymphocytes and to examine the expression of sIgM in vitro by human marrow that had been previously depleted of B cells by immunoadsorption. Marrow was derived from patients with acute leukemia in long-term remission off therapy and from a variety of controls. The pre-B-cell compartment was greatly expanded in the marrow of leukemia remission patients for more than 2 yr following cessation of therapy. A similar finding was noted in two patients with lymphoma who had also completed chemotherapy, but not in three with solid tumors prior to therapy. sIgM+ B cells appeared in cultures of sIg- marrow cells from leukemia patients, but not the controls, and only after exposure to Epstein-Barr virus (EBV). At least some of the sIgM+ lymphocytes also expressed cIgM and were probably derived from pre-B-cells. The results of this study (A) confirm that patients who have completed treatment for acute leukemia have a prolonged elevation of pre-B-cell proportions, (B) demonstrate that similar abnormalities may exist in patients with certain solid tumors following chemotherapy, and (C) suggest that a fraction of sIg- human marrow cells, perhaps pre-B-cells, bear a receptor for EBV and can be induced to express to sIgM in vitro.

Adolescent↗
PubMed1994

Antifungal prophylaxis with low-dose fluconazole during bone marrow transplantation. The Bone Marrow Transplantation Team.

The present study investigated the prophylactic efficacy of fluconazole at 100-200 mg/day against invasive fungal infections during bone marrow transplantation (BMT). During July 1990 to December 1991, all BMT recipients received antifungal prophylaxis with fluconazole at either 200 mg/day or 100 mg/day. Historical controls were those that received no antifungal prophylaxis (January 1989 to June 1990). Fungemia occurred in 4 of 112 fluconazole recipients and 8 of 79 controls (p < 0.05) prior to engraftment. Torulopsis (Candida) glabrata (three patients), Cryptococcus terreus and Candida tropicalis (mixed in one patient) caused fungemia in four patients in the fluconazole group; Candida albicans caused six of eight fungemic episodes in the controls. All three Torulopsis glabrata isolates were fluconazole-resistant. Colonization due to C. albicans was markedly diminished in the fluconazole group (19 of 112 patients versus 53 of 79 controls). T. glabrata, on the other hand, was a more common colonizing organism in the fluconazole group (36 of 112 vs 10 of 79). The frequency of isolating C. albicans and/or T. glabrata was significantly different between fluconazole and control groups (p < 0.0001). Empiric use of amphotericin B therapy was markedly reduced in the fluconazole group (4.5% vs 34%; p < 0.0001). Fluconazole at 200 mg/day or 100 mg/day appeared equally effective. Fluconazole at a daily dose of 100 mg or 200 mg as antifungal prophylaxis during BMT: (1) significantly reduced the frequency of systemic fungal infections, (2) markedly reduced colonization and infection due to C. albicans, and (3) markedly reduced the need for empiric amphotericin B therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1997

Effects of cyclosporin A on hepatitis C virus infection in bone marrow transplant patients. Bone Marrow Transplantation Team.

The hepatitis C virus (HCV) infection has, in general, been considered not to affect liver function severely during the course of bone marrow transplantation (BMT) except for late hepatitis which coincided with a decrease in immunosuppressive therapy. We examined serial sera of two patients with positive HCV antibody who underwent allogeneic BMT and found that while the dose of cyclosporin A tapered off, the serum concentration of HCV core protein increased before the occurrence of hepatitis. This suggests that viral reactivation and growth might be one of the important mechanisms of hepatitis after BMT in patients with positive HCV antibody.

Adult↗
PubMed1976

[Histological examinations of late changes of bone marrow and bone following local fractionated gamma irradiation in patients with genital carcinoma (author's transl)].

In 25 patients iliac crest biopsies have been taken after radiation therapy of genital carcinoma. The radiation doses in the biopsied region ranged up to about 3,000 rads. The time interval from the end of radiation until the control biopsy was 2 months or longer, up to 25 years. The immediate consequences of the radiation, compared with the pretherapeutic picture, have been analyzed in an earlier study (Beil et al., 1974). By histomorphotometric analysis of the samples it can be shown that a more or less severe atrophy of the bone marrow is persisting in the irradiated area for years. The atrophy is accompanied either by normal or increased bony trabecularization, together with increased osteoblastic and -clastic activity. These disturbances are likely to depend of a chronic distortion of the marrow capillarization, which may be influenced by the individual RES activity; different types of the reticuloendothelial response can be demonstrated in our material. Whether this response has a bearing regarding the prognosis of the tumours condition itself remains a matter of speculation, to be proved by further investigations.

Aged↗
PubMed1987

Bone formation in organ cultures of bone marrow.

Bone formation in organ cultures of intact marrow fragments from mouse is described. Marrow explants were cultured on the top surface of a millipore filter at a gas-liquid interface. Observations with both light- and electron microscopes demonstrated the formation of a well-organised trabecular matrix lined with osteoblast-like cells. The tissue and cells were positive for alkaline-phosphatase activity. Large amounts of thick, well-banded collagen fibrils and matrix vesicles typical of those found in bone were present. The tissue became mineralised in the presence of 10 mM Na-beta-glycerophosphate; in its absence a similar trabecular matrix developed but mineralisation did not take place.

Animals↗
PubMed2005

Treatment of senile osteoporosis in SAMP6 mice by intra-bone marrow injection of allogeneic bone marrow cells.

A substrain of the senescence-accelerated mouse, SAMP6 (senescence-accelerated mouse prone 6), spontaneously develops osteoporosis early in life. Therefore, this strain is a useful animal model for developing new strategies for the treatment of osteoporosis in humans. We succeeded in treating osteoporosis in SAMP6 mice after the onset of this disease, using a newly developed method of bone marrow transplantation (BMT): Allogeneic bone marrow cells obtained from normal mouse strains were directly injected into the bone marrow cavity of irradiated SAMP6 mice (intra-bone marrow BMT [IBM-BMT]). After the treatment with IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived cells, and bone marrow stromal cells were also found to be of donor origin. The treated SAMP6 mice showed histologically-normal trabecular bone. In addition, bone mineral density and urinary deoxypiridinoline, a hallmark of bone destruction, were normalized. When the message levels of cytokines (tumor necrosis factor alpha, interleukin-6 [IL-6], IL-11, and receptor activator of nuclear factor-kappa B ligand [RANKL]) were examined, IL-11, RANKL (from bone marrow stromal cells), and IL-6 (from osteoclasts), which regulate bone remodeling, were restored to levels similar to those in normal B6 mice. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment were normalized after IBM-BMT, resulting in an amelioration of the imbalance between bone absorption and formation.

Amino Acids↗
PubMed2006

[A clinical study on implantation of autologous bone marrow mononuclear cells after bone marrow stimulation for treatment of lower limb ischemia].

OBJECTIVE: To observe the clinical efficiency of the implantation of the autologous bone marrow mononuclear cells for treatment of lower limb ischemia after the bone marrow stimulation. METHODS: From May to December 2005, 43 ischemic limbs in 35 patients (23 males, 12 females; aged 34-90 years,averaged 71.3 year) were treated. Of the 35 patients, 30 had diabetic lower limb ischemia with 38 lower ischemic limbs, 2 had atherosclerosis obliterans with 2 ischemic lower limbs, and 3 had thromboangiitis obliterans with 3 ischemic lower limbs. Five patients with 5 ischemic limbs were in stage I lower limb ischemia (intermittent claudication), 15 patients with ischemic 19 limbs were in stage II (rest pain), 9 patients with 12 ischemic limbs were in stage IIIa (ulceration), and 6 patients with 7 ischemic lower limbs in stage IIIb (gangrene); 88.4% of all the ischemic lower limbs (38/43)had a pain, 79.1% (34/ 43) had coldness, and 69.8% (30/43) had limb numbness. The bone marrow of each patient was stimulated by an injection of the recombinant human granulocyte-macrophage colony-stimulatory factor (GSF), 300 microg/d for 2-3 days. The bone marrow 130-200 ml was drawn from the iliac spine and the mononuclear cells were obtained. Each patient received implantation of the autologous bone marrow mononuclear cells by an intramuscular injection, an arterial intraluminal injection or a combined injection of the two routes. RESULTS: The pain relief was found in 94.7% of the ischemic lower limbs, and pain improvement in 97.1% . Relieved numbness was found in 93.3%. The distance of the claudication was increased by all the ischemic limbs. An increase in the ankle/ brachial index (ABI) was found in 47.9%. The transcutaneous oxygen pressure (TcPO2) increased in 92.3%. The ulcer heal rate was 9.1% (1/11). Markedly-reduced ulcer wound was found in 27.3% (3/11). The amputation rate was 6.3% (3/48). Arterial angiography revealed that there was a new collateral vessel formation in 91.2%. Complications were as follows: fever and mild fatigue developed respectively in 1 patient after the bone marrow stimulation, but relieved by themselves. Acute but mild myocardial infarction was found in 1 patient with a slight precordial pain and elevation of myocardial enzymes 1 week after transplantation of the bone marrow mononuclear cells, but recovered after medical treatment. The follow-up averaged 5 months. According to the subjective criteria, the overall efficacy was 90%. ABI increased in 62.5% of the patients after operation and the value of TcPO2 was higher in 90% of the patients after this kind of therapy. Arterial angiography revealed a new collateral vessel formation in 90.5% of the 21 ischemic limbs. The foot ulcer healed in 7 and obviously improved in 3. Three of the foot ulcer patients were discharged 2-3 months after the amputation was performed on the diseased toes. CONCLUSION: Implantation of the autologous bone marrow mononuclear cells after the bone marrow stimulation of treatment of the lower limb ischemia has advantages of less marrow aspiration, more mononuclear cell content, satisfactory short-term effect, and relatively high safety. It is a new method of treating the lower limb ischemia besides the autologous bone marrow and peripheral blood mononuclear cell implantation. The long-term effect of this method needs a further study.

Adult↗
PubMed2001

A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission.

Intensive, myelosuppressive therapy is necessary to maximize outcomes for patients with acute myeloid leukemia (AML). A comparison was made of 3 aggressive postremission approaches for children and adolescents with AML in a randomized trial, CCG-2891. A total of 652 children and adolescents with AML who achieved remission on 2 induction regimens using identical drugs and doses (standard and intensive timing) were eligible for allocation to allogeneic bone marrow transplantation (BMT) based on matched related donor status (n = 181) or randomization to autologous BMT (n = 177) or to aggressive high-dose cytarabine-based chemotherapy (n = 179). Only 115 patients (18%) refused to participate in the postremission phase of this study. Overall compliance with the 3 allocated regimens was 90%. At 8 years actuarial, 54% +/- 4% (95% confidence interval) of all remission patients remain alive. Survival by assigned regimen ("intent to treat") is as follows: allogeneic BMT, 60% +/- 9%; autologous BMT, 48% +/- 8%; and chemotherapy, 53% +/- 8%. Survival in the allogeneic BMT group is significantly superior to autologous BMT (P =.002) and chemotherapy (P =.05); differences between chemotherapy and autologous BMT are not significant (P =.21). No potential confounding factors affected results. Patients receiving intensive-timing induction therapy had superior long-term survival irrespective of postremission regimen received (allogeneic BMT, 70% +/- 9%; autologous BMT, 54% +/- 9%; chemotherapy, 57% +/- 10%). Allogeneic BMT remains the treatment of choice for children and adolescents with AML in remission, when a matched related donor is available. For all others, there is no advantage to autologous BMT; hence, aggressive nonablative chemotherapy should be used.

Actuarial Analysis↗