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At least 163 records · Page 9Linked to original sources
PubMed1993

In vitro purging of bone marrow with mafosfamide synergizes with in vivo chemotherapy to delay the hematological recovery in a murine model of autologous bone marrow transplantation.

Very long-lasting leukopenias and thrombocytopenias have been observed in patients submitted to transplantation of autologous bone marrow incubated in vitro with cyclophosphamide derivatives. With the aim of evaluating the contribution of in vitro exposure of bone marrow to mafosfamide (Asta-Z) and of in vivo chemotherapy given before bone marrow collection in these cytopenias, we designed a murine model of syngeneic bone marrow transplantation including treatment of donor and recipient mice with high doses of cyclophosphamide and in vitro exposure of the bone marrow transplant to Asta-Z. Blood platelets and leukocytes, medullary splenic colony forming unit (CFU-S), committed megacaryocytic (CFU-Meg) and granulomacrophagic (CFU-GM) precursor cell recovery was followed up to 56 days posttransplant. The data indicate that in vitro exposure of bone marrow to Asta-Z before reinfusion increases the delay in platelet recovery already induced by the chemotherapy given to donor mice and is specifically responsible for the prolongation of leukopenia. In recipient bone marrow, a synergy between the ablative effect of the in vitro treatment of bone marrow graft and the chemotherapy given to donors and recipients on CFU-S, CFU-Meg and CFU-GM was found.

Animals↗
PubMed1992

Use of photosensitive, antibody directed liposomes to destroy target populations of cells in bone marrow: a potential purging method for autologous bone marrow transplantation.

Liposomes containing the photosensitive dye sulphonated aluminium phthalocyanine (AlSPc) were coupled to polyclonal sheep anti-mouse-Ig antibody and bound to cells coated with specific mouse monoclonal antibody. When illuminated with red light, the AlSPc in the liposomes was activated to produce singlet oxygen and the antibody and liposome targeted cells were destroyed. DW-BCL cells (an Epstein Barr virus immortalised B-cell line) were targeted with an anti-B-cell antibody (8A) and killed specifically, both alone and in the presence of bone marrow mononuclear cells (BM-cells), without phototoxic effects on the untargeted bone marrow CFU-GM progenitor cells. The presence of an excess of non-target cells did not interfere with antibody and liposome binding, or light access to target cells. Similar results were obtained with T-lymphocytes as target cells using anti-CD3 antibody. Specific targeting to the B-cells was demonstrated in the cell mixtures by use of fluorescent microscopy combined with a sensitive technique to detect low levels of AlSPc fluorescence, a cooled charge couple device (CCD) camera. This was also able to show low levels of non-specific background binding of AlSPc to BM-cells and a small population of cells that took up AlSPc in the absence of antibody. The latter were shown to be monocytes by flow cytometry.

Bone Marrow↗
PubMed1999

The use of soybean agglutinin (SBA) for bone marrow (BM) purging and hematopoietic progenitor cell enrichment in clinical bone-marrow transplantation.

Soybean agglutin (SBA) is a plant lectin that has been used to fractionate bone marrow cells. It binds bone marrow mononuclear cells, including mature myeloid, erythroid, and lymphoid cells, but has very low binding affinity and no toxic effect to the human hematopoietic cells. In this article we describe the possibilities of enriching bone-marrow-derived CD34+ hematopoietic progenitor cells using SBA. As the method is simple and elegant. SBA is of vast importance to the field of clinical bone marrow transplantation.

Adult↗
PubMed1996

Dibutyl phthalate purged autologous bone marrow transplant in the treatment of leukemia.

It has been proved that di-N-butyl phthalate (DBP) is singular in killing leukemic cells selectively or accelerating the deterioration of residual leukemic cells in long-term marrow culture in vitro. Based on this principle, the DBP-purged autologous bone marrow transplant has been applied to the treatment of a group of 14 patients suffering from acute nonlymphocytic leukemia. After 5-10 days of in vitro co-culture of marrow cells with DBP at a concentration of 50 micrograms/ml, the recovery of total nucleated cells and the amount of CFU-GM were 67.5% and 68.1%, respectively. In all patients, the reconstitution of hematopoiesis was observed after pre-conditioning and transfusion of purged marrow cells. Among these, two patients had a relapse, two patients died from complications of transplant, one patient died from non-leukemic disease, and the others are all alive and free of disease; the mean survival time as calculated recently was 15 months. These preliminary clinical data support that marrow culture in the presence of DBP is a safe and effective measure for treating leukemia in purged autologous bone marrow transplant.

Adolescent↗
PubMed1992

Treatment of recurrent and refractory pediatric solid tumors with high-dose busulfan and cyclophosphamide followed by autologous bone marrow rescue.

PURPOSE: The purpose of this study was to determine the toxicities of and responses to high-dose busulfan and cyclophosphamide with autologous bone marrow transplant (ABMT) in patients with recurrent or refractory pediatric solid tumors. PATIENTS AND METHODS: We treated 18 patients (ages, 2 to 38 years; median, 14) who had tumors that were resistant to conventional chemotherapy and radiotherapy with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg. Seventeen patients received bone marrow purged with 4-hydroperoxycyclophosphamide; one received unpurged marrow. RESULTS: Despite extensive prior treatment, including radiotherapy in 16 patients, toxicity generally was acceptable. For seven patients with measurable disease, there were three partial responses of 2, 10, and 20 months' duration, three patients with stable disease (SD), and one early, toxic death. Of the 11 patients with no measurable disease at the time of transplantation, one patient with osteosarcoma continues in remission at 57+ months and one third of the patients survived for at least 16 months. Mucositis was the predominant nonhematopoietic toxicity. CONCLUSION: Although the high-dose busulfan and cyclophosphamide combination showed modest activity, changes in the preparative regimen should be considered to improve the response rate in refractory tumors.

Adolescent↗
PubMed1997

Autologous stem cell transplantation for solid tumors in children.

The dose-effect relationship in pediatric oncology conventional chemotherapy is emphasized. Rationales for the use of megatherapy protocols with stem cell support and associated procedures are given. It has been more than 15 years since this approach was used in neuroblastoma, and it has subsequently been applied to most of advanced, common childhood solid tumors. The ongoing use of new strategies for dose intensification with peripheral blood stem cell or autologous purged bone marrow rescue has raised expectations for cure. To date, results of megatherapy followed by autologous stem cell reinfusion are encouraging in metastatic neuroblastoma and Ewing's sarcoma, with an increase in event-free survival rates of about 30% as compared with that of conventional treatments. However, with the exception of metastatic neuroblastoma, there is still no proven role for this treatment strategy. Thus, there is still an urgent need for international collaboration to design randomized studies that could rapidly address the issue of these expensive and high-morbidity procedures in childhood cancer.

Bone Marrow Purging↗
PubMed1992

Purging of autologous bone marrow for transplantation: the protection and selection of the hematopoietic progenitor cell.

Autologous bone marrow transplantation (ABMT) is the treatment of choice for selected patients with acute myelogenous leukemia, non-Hodgkin's lymphoma, and poor prognosis breast cancer. A possible limitation of this approach is that clonogenic tumor cells could be collected and infused back into the patient along with the normal bone marrow. The major emphasis in our laboratory has been the development of marrow purging regimens for breast cancer patients. This paper describes two investigative approaches hematopoietic progenitor cell protection and selection. We describe how the use of G-CSF in the patients who receive positively selected marrow shortens the rate of engraftment.

Bone Marrow Purging↗
PubMed1991

[Autologous bone marrow transplantation after purging by low molecular weight natural tumor suppressor in long-term marrow culture in vitro: report on 2 cases].

In the light of high sensitivity of fresh bone marrow blast progenitor of human myeloid leukemia (L-CFU) towards the action of low molecular tumor suppressor isolated from human fetal liver, massive bone marrow was aspirated from the patients suffering from acute myeloid leukemia at the stage of first complete remission and cocultured in a long-term bone marrow culture system for 9 days. The purged marrow cells were then re-infused into the patients after preconditioning with large doses of cytotoxin and acute ionizing irradiation. Hematopoiesis was reconstituted due to the autologous transplantation in vivo. After the autologous bone marrow transplantation without chemical treatment, two cases are still survival with the time of more than 17 and 15 months respectively.

Adult↗
PubMed1994

Comparative effects of amifostine (Ethyol) on normal hematopoietic stem cells versus human leukemic cells during ex vivo purging in autologous bone marrow transplants.

The protective action of amifostine (Ethyol, US Bioscience, Inc. West Conshohocken, PA) against the toxic effects of cyclophosphamide derivatives on the normal progenitor/stem cell pool was investigated. Early and late normal progenitor/stem cells were studied in the presence of placenta-conditioned medium (placenta-conditioned medium-granulocyte-macrophage colony-forming units); in the presence of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin-3, erythropoietin, stem cell factor (5R-CFU-GM); stimulated granulocyte-macrophage colony-forming and in a long-term culture-initiating cell assay. The preservation of an antileukemic effect was investigated by growing leukemic progenitor cells in the presence of phytohemagglutinin and leukocyte feeder layer with or without 25u interleukin-2. In 10 of 13 cases, a statistically significant (P < .05) protective effect was found on PCM-granulocyte-macrophage colony-forming units, in four of 10 cases on factor-stimulated granulocyte-macrophage colony-forming units, and in two of six cases on long-term culture-initiating cell. In contrast, amifostine exhibited no protective effect (none of nine cases) on leukemic progenitor cells. From the experimental data, it seems that amifostine is able to protect human normal progenitor/stem cells from cyclophosphamide derivative toxicity, while preserving their antileukemic effects. The therapeutic usefulness of such protection in autologous bone marrow transplantation with purged marrow is obvious.

Amifostine↗
PubMed1995

Natural killer cell regeneration after transplantation with mafosfamide purged autologous bone marrow.

Autologous bone marrow transplantation (ABMT) is used increasingly for the treatment of acute leukemias, lymphomas and solid tumors. Since ABMT is burdened by high risk of relapse, mafosfamide or 4-hydroperoxycyclophosphamide chemical marrow purging is employed. Mafosfamide acts by exerting a potent cytotoxic effect and by promoting apoptosis of leukemic cells. A third proposed mechanism of action involves an effect on immune regeneration in vivo. It was the aim of this study to investigate natural killer (NK) cell regeneration in a group of patients undergoing mafosfamide-purged ABMT. Fifteen patients (8 acute myelogenous leukemia, AML; 4 acute lymphoblastic leukemia, ALL; 3 non-Hodgkin's lymphoma, NHL) were treated with high-dose chemotherapy followed by transplantation with marrow purged with mafosfamide. Prior to ABMT and at different intervals thereafter, NK cell number and function were studied by evaluating the percentage of circulating CD16 positive cells and cytotoxic activity against the leukemic cell line, K562. In comparison to pre-ABMT values, AML patients showed a significant increase in cytotoxic activity, expressed as percentage of chromium release (42.5 +/- 3 vs 32.5 +/- 6, P < or = 0.025 at 4 months) which still persisted at 12 months post-ABMT (54 +/- 6, P < or = 0.05). The behavior of NK functional activity was paralleled by an increase of the percentage of CD16-positive cells (8.4 +/- 2.2 vs 5 +/- 1.3, P < or = 0.05 at 4 months; 12.8 +/- 2.4, P < or = 0.005 at 12 months post-ABMT). Similar significant and long-lasting increments in NK cells were also found in NHL patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1997

Photochemical purging of autologous bone marrow grafts: assessment of damage to stem cells and the microenvironment in long-term marrow cultures.

Toxicity of merocyanine 540 (MC540) was assessed in long-term (Dexter-type) bone marrow cultures and in a short-term in vitro clonal assay of fibroblast colony-forming cells (CFU-F). Exposure of freshly explanted mouse bone marrow cells to MC540 (15 micrograms/ml) and white light (fluence: 126 kJ/m2) reduced CFU-F by approximately 2 logs but did not abrogate the cells' capacity to establish and maintain long-term bone marrow cultures. Fat cells were rare or absence in adherent layers established with photosensitized bone marrow cells but the cultures' capacity to generate non-adherent cells, granulocyte/macrophage progenitors (CFU-GM), and early erythroid progenitors (BFU-E) was only moderately (28-36%) reduced.

Animals↗