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PubMed1994

Second infusion of bone marrow for treatment of graft failure after allogeneic bone marrow transplantation.

The availability of hematopoietic growth factors has introduced a new therapeutic modality to the treatment of graft failure after bone marrow transplantation (BMT). However, the clinical value of other therapeutic approaches to graft failure has not been reported in detail. We have studied the outcome of second infusions of BM for treatment of primary and secondary graft failure in 33 patients who received an allogeneic BMT at our institution between 1974 and 1992. Patients had received BM from a related (n = 28) or unrelated (n = 5) donor for hematological malignancy or BM failure. After primary graft failure, 57% (12 of 21) of reinfused patients engrafted and the Kaplan-Meier estimate of survival at 1 year is 24% (CI 6-42%). After secondary graft failure, 33% (4 of 12) of reinfused patients engrafted and survival is 25% (CI 0-50%) at 1 year. Infection, predominantly fungal, was the most frequent cause of death. Acute or chronic graft-versus-host disease (GVHD) developed in 52% of evaluable reinfused patients. We conclude that reinfusion of donor marrow can be an effective intervention in the treatment of primary and secondary graft failure. These data can serve as a comparative historical experience for the assessment of hemopoietic growth factors in the treatment of graft failure.

Acute Disease↗
PubMed1976

Effects of beta-adrenergic stimulation on bone-marrow function in normal and sublethally irradiated mice. I. The effect of isoproterenol on cAMP content in bone-marrow cells in vivo and in vitro.

The effect of isoproterenol (IPR) on bone-marrow cAMP content was investigated in vivo and in vitro. In unirradiated CFW mice, the bone-marrow cAMP content was found to be elevated by the administration of noradrenaline, adrenaline and isoproterenol. After IPR administration, the increase in cAMP was biphasic with maxima at 1 and 15 min. An increase in cAMP content was also noted in bone-marrow of sublethally-irradiated mice, but no further increase was observed 15 min after the administration of IPR. Elevation of cAMP by either IPR or radiation was prevented by pretreatment with the beta-adrenergic blocking agent--propranolol. IPR was also effective in increasing the cAMP content when added to suspension of bone-marrow cells. This effect was abolished by propranolol. IPR did not increase cAMP levels in bone-marrow cells isolated from irradiated animals. The results suggest that the differentiated bone-marrow cells have beta-adrenergic receptors.

Adrenergic beta-Agonists↗
PubMed2004

Rescue of interferon induced bone marrow aplasia in a patient with chronic myeloid leukemia by allogeneic bone marrow transplant.

A patient with chronic phase Philadelphia chromosome positive CML, developed severe protracted bone marrow hypoplasia after interferon therapy. This complication did not respond to two courses of immunosuppressive therapy with anti-thymocyte globulin, cyclosporin A and prednisone. The patient continued to be transfusion dependent with persistence of Philadelphia chromosome. Allogeneic BMT restored normal hematopoeisis.

Adult↗
PubMed2002

Differences in the expression of neurokinin receptor in neural and bone marrow mesenchymal cells: implications for neuronal expansion from bone marrow cells.

The neurokinin-1 (NK-1) receptor interacts with peptides that belong to the tachykinin family. NK-1 is inducible in bone marrow (BM) stroma. In neural cells, its expression is high to constitutive. Screening of three cDNA libraries indicated that this different in NK-1 expression in neural and BM cells could not be explained by differences in the cDNA sequence. Analyses the 5' flanking sequence in BM stroma and three neural cell lines indicated that sequence +1/+358 relative to the transcription start (TS) site could account for the differences in NK-1 expression. Particular cytokines could reverse the repressive effects of region +1/+358 in BM stroma. The effects of NF-kappa B and cAMP activators were studied in stromal cells using a dominant negative inhibitor of NF-kappa B (I kappa B) or a repressor of CRE activators (ICERII gamma). The results showed that their effects of these transcription factors depended on the stimulating cytokine. This study provides insight into the tissue-specific differences in the expression of the NK-1 gene.

5' Untranslated Regions↗
PubMed1992

The meaning of quality of life for bone marrow transplant survivors. Part 1. The impact of bone marrow transplant on quality of life.

Quality of life (QOL) is an important concept in cancer nursing and has particular significance for bone marrow transplant (BMT). BMT survivors are faced with the demands of acute transplant symptoms as well as chronic illness demands posttransplant. The purpose of this study was to explore the concept of QOL for BMT survivors and to gain understanding of nursing interventions that may improve QOL in this population. The conceptual framework for this study was derived from the model of QOL developed by Ferrell, Grant, and Padilla (1989) that depicts the QOL domains of physical well-being, psychological well-being, social concerns, and spiritual well-being. This qualitative study consisted of a one-time interview of 119 BMT survivors using six open-ended questions. The items were based on previous research of the authors and content validity was established by a panel of BMT experts. Content analysis was performed on verbatim written responses to six questions regarding BMT and QOL. Part one of this two-part report provides analysis based on the questions regarding the meaning of QOL to BMT survivors and the impact of BMT on QOL.

Adult↗
PubMed1982

Treatment of donor bone marrow with OKT3 (PAN-T monoclonal antibody) for prophylaxis of graft-vs.-host disease (GvHD) in histocompatible allogeneic bone marrow transplantation (BMT): a pilot study.

Ten consecutive patients ranging in age from seven to 34 years undergoing bone marrow transplantation from histocompatible siblings for treatment of hematologic malignancy were entered into a pilot study designed to test the safety of OKT3 pretreatment of donor bone marrow for prevention of graft-vs.-host disease. Concentrated donor bone marrow specimens containing a mean of 6.5 X 10(8) nucleated cells/kg recipient weight were treated with 1 mg of OKT3 at 4 degrees C for 30 min prior to administration to the recipient. In vitro immunofluorescent studies confirmed that all OKT3+ cells in bone marrow had effectively bound antibody. Furthermore the addition of neonatal rabbit complement in vitro decreased the proliferative responses of donor bone marrow cells to phytohemagglutinin and concanavalin A (Con A) to less than or equal to 4% of untreated bone marrow. No significant complications resulted from the administration of OKT3 and all recipients engrafted after a mean duration of 22 days. Nine of the 10 patients survived for more than 100 days after marrow transplantation. However, five of the 10 patients developed acute graft-vs.-host disease and required steroid therapy. While this pilot study suggests that OKT3 can be used safely in the bone marrow transplantation setting, further modification of our OKT3 treatment procedure will be necessary to completely eradicate graft-vs.-host disease in histocompatible bone marrow transplantation.

Acute Disease↗
PubMed1988

Y-body study in bone marrow precursors, peripheral blood cells and alveolar macrophages for demonstration of haemopoietic engraftment in allogeneic bone marrow transplantation.

The value of Y-body study for assessment of haemopoietic engraftment was analyzed in 50 consecutive patients submitted to allogeneic bone marrow transplantation (BMT) (sex-matched in 28 cases, sex-mismatched in 22). The study was performed weekly on bone marrow and peripheral blood smears in all cases, and alveolar macrophages were also studied in 15 patients in whom bronchoalveolar lavage was carried out because of concurrent respiratory disturbances. The analysis was performed blindly by 2 independent observers. In both sex-matched and sex-mismatched cases there was an absolute concordance between recipient and donor Y-body results, as well as with the simultaneous cytogenetic study. The engraftment of erythroid and granulopoietic lines was documented at day +14 in all cases of sex-mismatched BMT, whereas megakaryocyte and lymphocyte take was demonstrated at d +21. On the other hand, the results from alveolar macrophages were in accordance with those obtained in the simultaneous study of bone marrow precursors after BMT. The above results indicate that Y-body analysis is a simple and useful tool for the demonstration of bone marrow take in sex-mismatched BMT.

Blood Cells↗
PubMed1992

Engraftment of leukocyte subsets following autologous bone marrow transplantation in acute myeloid leukemia using anti-myeloid (CD14 and CD15) monoclonal antibody-purged bone marrow.

The cell surface phenotype of leukocyte subsets during reconstitution following autologous bone marrow transplantation (ABMT) using bone marrow purged with anti-myeloid monoclonal antibodies (MoAbs) and complement (C') was evaluated in 20 patients with acute myeloid leukemia (AML). Repopulation of B and T lymphocytes, natural killer (NK) cells, and myeloid cells was assessed by phenotypic analysis using two-color cytofluorography of peripheral blood mononuclear cells (PBMNC) at several time points up to 2 years post-transplantation. In spite of removal of the majority of monomyeloid cells of the autograft by purging with anti-CD14 and anti-CD 15, engraftment occurred rapidly. The myeloid cells appeared normal by surface phenotype. An early rise in NK cells, characterized by expression of CD57 and CD 16, was seen. The CD4:CD8 ratio remained low throughout the study period, primarily due to a persistently low CD4 level. ABMT using bone marrow purged with the anti-myeloid MoAbs PM-81 and AML-2-23 and C' resulted in prompt engraftment of neutrophils. Although there was a prolonged time for recovery of lymphocyte subsets, this did not result in an increased risk of early infectious complications. Late infectious complications post-transplantation were limited to herpes zoster infection in one patient 18 months post-transplantation, and bacterial meningitis in that same patient 2 months later. This study demonstrates that ABMT in patients with AML using bone marrow purged with the anti-myeloid MoAbs PM81 (anti-CD15) and AML-2-23 (anti-CD14) and C' results in rapid hematologic engraftment and delayed phenotypic immunologic reconstitution without significant acute or chronic clinical toxicities.

Adolescent↗
PubMed2000

Bone marrow accessory cells regulate human bone precursor cell development.

OBJECTIVE: Much remains to be learned about the intimate relationship between bone marrow and its surrounding tissue: the bone. We hypothesized that bone marrow accessory cell populations might regulate the development of human bone precursor cells. MATERIALS AND METHODS: We used immunologic phenotyping, and isolation methods to fractionate subpopulations of nonadherent, low-density (NALD) human bone marrow cells. These cells were examined for their ability to support the serum-free survival, proliferation, and expression of bone proteins by highly purified populations of human bone precursor cells. Quantitative assessment of the accessory cell populations as well as human bone precursor cells phenotype was performed using multiparameter flow cytometry. Bone protein expression was evaluated by immunocytochemistry, Western analysis, and enzymatic analysis (for alkaline phosphatase activity). RESULTS: Human bone marrow contains a cell population that stimulates the development of purified bone precursor cells. Feeder-layer studies demonstrate that these osteopoietic accessory cells (OACs) do not require cell-cell interaction to promote bone precursor cell development but, rather, produce soluble molecules responsible for their effects. Flow cytometric analyses reveal that bone marrow derived B cells, T cells, macrophages, natural killer cells, and endothelial cells do not produce this stimulatory factor. The (growth) factor cannot be replaced by addition of exogenous cytokines. The isolation of human transforming growth factor beta receptor type II (TGF-betaRII)-positive cells increases OAC-specific activity in bone cell ex vivo expansion cultures. Moreover, isolation of OAC bone marrow cells characterized by high TGF-betaRII expression, relatively low cellular complexity, and small size yields a population that is highly enriched for OACs. CONCLUSION: We conclude that human bone marrow contains a population of OACs that are an obligate requirement for the early phases of bone cell development ex vivo.

Antigen-Presenting Cells↗
PubMed1990

Acute megakaryoblastic leukemia with massive myelofibrosis: complete remission and reversal of marrow fibrosis with allogeneic bone marrow transplantation as the only treatment.

We report results of allogeneic bone marrow transplantation in an 8-year-old boy with acute megakaryoblastic leukemia characterized by intense fibrosis together with 20% blast cells in the bone marrow, who was transplanted without preceding chemotherapy for remission induction. Conditioning comprised cytosine arabinoside, cyclophosphamide and total body irradiation. The donor was his HLA-identical sister. The patient is well with minor chronic graft-versus-host disease and normal hematologic values 670 days post-transplant.

Bone Marrow↗
PubMed2005

Unrelated bone marrow transplantation for beta-thalassemia patients: The experience of the Italian Bone Marrow Transplant Group.

Bone marrow transplantation (BMT) remains the only potentially curative treatment for patients with thalassemia major. However, most candidates for BMT do not have a suitable family donor. In order to evaluate whether BMT from an HLA-matched unrelated volunteer donor can offer a probability of cure comparable to that obtained when the donor is a compatible sibling, we carried out a study involving 68 thalassemia patients transplanted in six Italian BMT Centers. Thirty-three males and 35 females (age range, 2-37 years; median age, 15) were transplanted from unrelated volunteer donors, all selected using high-resolution molecular typing of both HLA class I and II loci. Fourteen patients were classified in risk class 1; 16 in risk class 2; and 38 in risk class III of the Pesaro classification system. Nine patients (13%) had either primary or secondary graft failure. Fourteen patients (20%) died from transplant-related causes. Grade II-IV acute graft-versus-host disease (GVHD) developed in 24 cases (40%), and chronic GVHD in 10 cases (18%). Overall survival (OS) in the cohort of 68 patients was 79.3% (CI 67-88%), whereas the Kaplan-Meier estimates of disease-free survival (DFS) with transfusion independence was 65.8% (CI 54-77%). In the group of 30 thalassemic patients in risk classes 1 and 2, the probability of OS and DFS were 96.7% (CI 90-100%) and 80.0% (CI 65-94%), respectively, whereas in the 38 patients in class 3 OS was 65.2% (CI 49-80%) and DFS was 54.5% (CI 38-70%). These data show that when donor selection is based on stringent compatibility criteria, the results of unrelated transplantation in thalassemia patients are comparable to those obtained when the donor is a compatible sibling.

Adolescent↗
PubMed1998

Bone marrow composition and bone microarchitecture and turnover in blacks and whites.

We examined the relationship between bone histomorphometric variables versus marrow cellularity, marrow adiposity (among hemopoietic cells), and fatty degeneration (areas of only fat) of bone marrow in iliac crest bone samples from 98 normal black (n = 53) and white (n = 45) males and females. We found blacks to have greater marrow cellularity (p = 0.0001), less marrow adiposity (among hemopoietic cells, p = 0.0001), greater values for bone volume (p = 0.030), trabecular thickness (p = 0.002), and static bone turnover variables (osteoid volume, p = 0.001; osteoid surface, p = 0.001; osteoid thickness, p = 0.001; eroded surface, p = 0.0006) than whites. Marrow cellularity correlated positively with static bone turnover variables osteoid volume (r = 0.257, p = 0.011), osteoid surface (r = 0.265, p = 0.008), osteoid thickness (r = 0.217, p = 0.032), and eroded surface (r = 0.273, p = 0.007) when all 98 cases were analyzed together. These findings suggest that marrow cells may influence bone turnover. The extent of fatty degeneration, but not that of adipose tissue, increased with age in blacks (r = 0.476, p = 0.0003) and whites (r = 0.476, p = 0.001), as did bone loss. There was no racial difference in the extent of fatty degeneration. We conclude that the lesser extent of adiposity in blacks is a racial characteristic that is unaffected by aging, whereas fatty degeneration which may have partly occupied space vacated by bone loss, is an aging phenomenon, unrelated to race. Greater bone turnover in blacks may be expected to lead to more frequent renewal of fatigue-damaged bone, which together with sturdier bone structure may contribute to the lower fragility fracture rates in blacks.

Adult↗
PubMed1996

4-Hydroperoxycyclophosphamide purged autologous bone marrow transplantation in non-Hodgkin's lymphoma patients at high risk of bone marrow involvement.

Between June 1990 and January 1994, 19 patients with non-Hodgkin's lymphoma (NHL) at high risk for bone marrow involvement underwent 4-hydroperoxycyclophosphamide (4-HC) purged bone marrow transplantation. Eleven patients had low grade, seven intermediate grade and one high grade NHL and 7/19 patients had received three or more previous chemotherapeutic regimens. Four patients were transplanted in first partial remission (PR) and the remainder in responsive relapse. Fourteen patients had bone marrow (BM) involvement at diagnosis and/or at relapse. The median times to granulocyte and platelet recovery were 26 and 29 days, respectively. There were two toxic deaths and one complete responder developed secondary AML at 31 months post-BMT. Seventeen of 18 evaluable patients achieved a complete remission (CR) and one patient a PR. Fourteen patients (74%) are progression-free at a median follow-up of survivors of 34 months (range 29-55). The 3 year event-free (EFS) and overall survival (OS) probabilities are both 67%. No statistically significant difference was seen between EFS or OS and BM involvement or histologic grade at diagnosis. At 29 months, 4/7 patients with a morphologically involved BM harvest had relapsed or died compared to 1/12 patients with negative BM (P = 0.03). These results are encouraging and warrant further investigation of 4-HC purging in NHL.

Adult↗
PubMed1993

Report from the International Bone Marrow Transplant Registry and the North American Autologous Bone Marrow Transplant Registry.

The Statistical Center of the IBMTR/NAABMTR has expanded its role from collecting data on allogeneic and syngeneic transplants to the area of autologous bone marrow and blood cell transplantation given to support high-dose therapies for cancer. In diseases such as acute leukemia for which both allogeneic and autotransplants are performed, direct comparisons of outcomes of these therapies are now possible. The large number of cases that has accrued rapidly into the NAABMTR (over 9,000 since 1989) will allow us to use sophisticated statistical techniques to determine potential benefits and disadvantages in the rapidly growing area of autotransplantation.

Asia↗