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Biomedical subjects

F Beaujean

Publications and source records attributed to F Beaujean.

At least 37 records · Page 2Linked to original sources
PubMed1997

Stage IV neuroblastoma in patients over 1 year of age at diagnosis: consolidation of poor responders with combined busulfan, cyclophosphamide and melphalan followed by in vitro mafosfamide-purged autologous bone marrow transplantation.

In an attempt to improve the poor prognosis of poor responders with stage IV neuroblastoma, a new combined high-dose chemotherapy conditioning regimen was tested. Event-free and overall survival, as well as the incidence of complications, were analysed. Twenty-five children aged 12-146 months at diagnosis entered this study. All were in complete remission (CR) at the time of high-dose chemotherapy. Two or three different protocols had been necessary for them to achieve a CR. High-dose chemotherapy consisted of a combination of busulfan (600 mg/m2), cyclophosphamide (4400 mg/m2) and melphalan (140 mg/m2). It was followed by autologous bone marrow transplantation (ABMT). The bone marrow graft was purged in vitro with mafosfamide. The probability of event-free survival (EFS) at 5 years post-ABMT was 34%, compared to < 8% in a historical series. Toxicity was severe but manageable and 2 complication-related deaths were observed. Veno-occlusive disease was the most frequent extrahaematopoietic complication encountered, but its outcome was always favourable. By using a very intensive conditioning regimen consisting of a combination of three alkylating agents, the EFS of poor responders with metastatic neuroblastoma was improved and similar to that of good responders. When compared with a previously published similar series of patients, the improvement in survival appears probably related to intensification of the conditioning regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Abnormalities in the bone marrow of the iliac crest in patients who have osteonecrosis secondary to corticosteroid therapy or alcohol abuse.

UNLABELLED: The bone-marrow activity in the iliac crest of eleven patients who had idiopathic osteonecrosis of the hip and thirty patients who had osteonecrosis of the hip that was related to corticosteroid therapy (fourteen patients) or to alcohol abuse (sixteen patients) was compared with that in two groups of control subjects who did not have osteonecrosis (thirty-three healthy bone-marrow donors and thirty-four patients who had been managed with bone-marrow grafting for a non-union). Cultures of granulocyte-macrophage progenitor cells and fibroblast colony-forming units were performed to assess the activity of hematopoietic stem cells and stromal cells. The activity of stem cells in both the hematopoietic and the stromal compartment of the bone marrow was decreased in the patients who were receiving corticosteroids or who abused alcohol, as compared with that in the two groups of control subjects. The patients who had idiopathic osteonecrosis also had a decrease in bone-marrow activity compared with the control subjects. CLINICAL RELEVANCE: Our findings suggest that patients who are receiving corticosteroid therapy or who abuse alcohol have decreased activity of bone-marrow cells. Whether this decrease is related to the osteonecrosis could not be determined, as our study did not include control subjects who had a history of alcohol abuse or who were receiving corticosteroids but did not have osteonecrosis. However, it is possible that the reduced bone-marrow activity was related to the osteonecrosis, as patients who had idiopathic osteonecrosis also had decreased bone-marrow activity. The study of pathological alterations in the bone marrow outside the necrotic zone may provide important insights into the pathophysiology of osteonecrosis.

Adolescent↗
PubMed1997

[Bone marrow in patients with pseudarthrosis. A study of progenitor cells by in vitro cloning].

PURPOSE OF THE STUDY: The recent observations that osteoblasts develop from a stem cell found in the medullary stroma suggest that, as already suspected in classical histological studies, many consolidation mechanisms are based on bone marrow. Since cells characteristics can now be studied in tissue culture, it has become possible to investigate the activity of the bone marrow in non union. The working hypothesis for this study was: if the bone marrow plays a part in bony callus formation, bone marrow from non union site should manifest anomalous activity whatever the origin of the focus sampled. Therefore, the aim of this study was to seek in vitro, using cell cloning techniques, anomalies of bone marrow from non union site. MATERIALS: The study characterizes the bone marrow from 35 non union sites, not only with respect to the medullary stroma but also the hematopoietic compartment. In this study, we look for systemic anomalies which could explain susceptibility to non union, we also compare in vitro activity of bone marrow taken from non union with others samples taken from the iliac crest of the same patient. METHODS: The cell density in the bone marrow in these sites was studied in vitro with material taken from the non union site. Samples were taken by aspiration with a trocar located by image intensification. Assays of CFU-GM were chosen to quantify the hematopoietic activity of the marrow, and of CFU-F to quantify stroma cells activity. Cell densities in the non union site were compared to those in patients' own iliac crests, and also to iliac crests densities of a control population of bone marrow donors. RESULTS: The bone marrow of non union site contained low levels of progenitor cells. Especially surprising was that progenitors were also sparse in the bone marrow of the iliac crest of patients with non union, compared with control bone marrow donors. In several cases, certain general factors are probably responsible for the abnormally low levels of progenitor cells, not only in the non union site, but also in the iliac crest.

Adolescent↗
PubMed1997

[Pseudarthrosis treated by percutaneous autologous bone marrow graft].

PURPOSE: This study characterizes the bone marrow from 35 non union sites, not only with respect to the medullary stroma but also the hematopoietic compartment. In this study, we looked for systemic anomalies which could explain susceptibility to non union. We also compare the in vitro activity of bone marrow taken from non union sites with that of samples taken from the iliac crest, of the same patient. MATERIAL AND METHODS: We included 6 groups: 26 cases of post-traumatic non union. 2 cases of non union following arthrodesis of the knee for infected prosthesis, 1 case of a non union of a tibiotarsal arthrodesis. 4 cases of regenerated illizarov extensions, which showed no evidence of ossification three months after operation, 2 cases of patients suffering from congenital abnormalities. Samples were taken from a population of 30 "bone marrow donors", to act as controls for the iliac crest samples. RESULTS: Cell density in the iliac crest bone marrow of non union patients is significantly lower than that of controls (p < 0.01). In the hematopoietic compartment of the bone marrow, the number of progenitors (GM-CFU) obtained after culture of iliac crest bone marrow is consistently lower for patients presenting a non union than for controls (p < 0.01). Only infection of non union site (4 cases) seems to be associated with an increase in GM-CFU in the iliac crest. The difference in the average number of F-CFU obtained after culture of bone marrow from non union patients and from controls is lower but is nevertheless significant. 14 of the non union patients have less than half the F-CFU observed as normal in controls and 10 of them yielded less than one quarter. Out of these ten patients, in whom non union was associated with a marked abnormality in the number of F-CFU in the iliac crest (less than one quarter of the total obtained from controls), in 8 cases were other factor or disease which could account for the abnormality such as age (2 cases), clear alcoholic intoxication (1 case), heavy smoking (2 cases), history of chemotherapy (2 cases), and Lobstein's disease (1 case). The values found in non union sites and extension regenerated fibrous tissue suggest that there are relatively few F-CFU to differentiate into fibroblasts. In 12 out of 35 patients studied, the bone marrow generated no F-CFU. Same patients have abnormal low levels of F-CFU obtainable from their iliac crest bone marrow. The number of GM-CFU in fracture site is also extremely low. No local increases in GM-CFU levels are seen in septic focuses. The population of F-CFU and GM-CFU vary with time, in the same patient, at the same site of aspiration. Higher levels of osteogenic activity are seen at the beginning of extension. CONCLUSION: This study suggests that problems related to consolidation may be linked with an overall reduction of bone marrow progenitor cells, as a result of some general physiological problem (chemotherapy, smoking, alcoholic poisoning).

Administration, Cutaneous↗
PubMed1996

Characteristics of peripheral blood progenitor cells frozen after 24 hours of liquid storage.

Peripheral blood progenitor cells (PBPC) harvested for autologous transplantation are usually cryopreserved within 2-4 h of collection. However, there are conditions in which it would be useful to freeze PBPC after a liquid storage period. This study was performed to evaluate whether prior storage for just 24 h damages frozen PBPC. First, leukapheresis products were obtained from 9 patients and divided into three fractions. The first fraction was frozen within 2 h and used as a control. The second and the third fractions were stored either at 4 degrees C or at 22 degrees C for 24 h before freezing. Cell counts, CFU-GM values, and pH were studied after collection, after storage, and after cryopreservation. Similar results were obtained at 4 degrees C and 22 degrees C. However, pH decreased most markedly at 22 degrees C. Mean postcryopreservation CFU-GM recoveries were not significantly different and were, respectively, 74.03% (control), 96.39% (4 degrees C), and 80.33% (22 degrees C). These observations were confirmed in an additional study of frozen PBPC collected from 12 patients and previously stored for 24 h at 4 degrees C. These data indicate that blood progenitors may be stored for 24 h and subsequently frozen without quantitative and qualitative impairment.

Cryopreservation↗
PubMed1995

Effects of cryopreservation on the proliferation and anticoagulant activity of human saphenous vein endothelial cells.

Human saphenous veins were cryopreserved in 4% human albumin and 10% dimethyl sulfoxide. The effect of cryopreservation on endothelial cells was studied in terms of the anticoagulant activity of thrombomodulin and in terms of cell proliferation. After storage for 2 weeks at -150 degrees C, 0.45 +/- 0.07 x 10(5) endothelial cells/cm2 were detected in cryopreserved veins and 1.03 +/- 0.04 x 10(5) endothelial cells/cm2 in fresh veins (p < 0.01). The thrombin-catalyzed activation of protein C decreased after cryopreservation, indicating altered thrombomodulin activity in the endothelial cells. On a cell number basis, the release of soluble thrombomodulin was three times higher from the cryopreserved endothelium than from the fresh endothelium (p < 0.05). The amount of spontaneous release of von Willebrand factor from the endothelial surface was not significantly different between fresh and cryopreserved veins. Endothelial cells were cultured from fresh veins and from their cryopreserved counterparts. On plating of endothelial cells in primary culture, the number of adhered cells was 0.9 +/- 0.09 x 10(3) cells/cm2 from fresh veins and 0.25 +/- 0.03 x 10(3) cells/cm2 from cryopreserved veins (p < 0.01). The positive immunohistochemical stain for von Willebrand factor indicated that the endothelial cell character was maintained after cryopreservation. The endothelial desquamation with loss of anticoagulant function and the slow proliferation of surviving cells in vitro suggest an impaired endothelial healing in vivo. The loss of anticoagulant activity complicates the problems of the exposure of thrombogenic subendothelial matrix to blood in implanted cryopreserved veins.

Blood Coagulation↗
PubMed1995

Successful engraftment after autologous transplantation of 10-day cultured bone marrow activated by interleukin 2 in patients with acute lymphoblastic leukemia.

Disease recurrence remains the major problem in autologous bone marrow transplantation (BMT) for hematologic malignancies. To improve the therapeutic efficiency of autologous BMT, we investigated the use of autologous marrow activated in vitro with interleukin 2 (IL-2) to generate killer cells for in vivo purging. A feasibility trial was initiated in 5 patients with poor prognosis acute lymphoblastic leukemia, who were transplanted, after marrow ablative therapy, with autologous marrow cultured for 10 days with 10(3) units of IL-2/ml. A highly significant increase in NK activity and an induction of LAK activity were observed after incubation. Patients received 0.64 to 1.56 X 10(8) cultured BM cells/kg and 1.87 to 44.8 x 10(4) CFU-GM/kg. Four patients engrafted and achieved granulocyte counts > 0.5 x 10(9)/l on days 35, 24, 36 and 22 after transplant. Three of these patients showed platelet recovery to > 50 x10(9)/l on days 25, 42 and 40 after transplant. One patient remained thrombocytopenic until relapse. One patient died on day 12 after transplant. This study demonstrates that cultured BM activated with IL-2 can be used successfully for hematological rescue in the clinical setting.

Bone Marrow↗
PubMed1994

[Transfusion and alloimmunization in sickle cell anemia patients].

Transfusion therapy for sickle cell anemia is limited by the development of antibodies to red cell antigens. The aim of this study was to evaluate whether transfusion of blood matched for antigens Rh and Kell would reduce the incidence of alloimmunization. We determined the transfusion history, red cell phenotype and development of alloantibodies in 173 patients with sickle all anemia who received transfusions. Forty nine patients were transfused exclusively with frozen red blood cells (RBL) matched for antigens Rh and Kell; the rate of alloimmunization was 8.2%; antibodies to the Jkb, Jka, Fya and S were developed; 1 patient developed 2 antibodies. In a control group of 124 patients who received standard red blood cells, the rate of alloimmunization was significantly increased to 30.6% (p < 0.05); antibodies against C, E, K, Fya were the most frequently developed and 19 patients (16%) developed antibodies reacting with different antigens. In the 2 groups, alloimmunization occurred after receiving a significantly different number of transfusions: mean 9 in the patients transfused with matched RBC and 32 in the control group. The influence of the kinetics of transfusion was not demonstrated. To assess the effect that racial differences might have on alloimmunization, comparison of the red cell phenotype of patients with that of a panel of unselected blood bank donors was performed: the patients had a significant decrease in the frequency of red cell antigens corresponding to most of the detected alloantibodies JkB, C, S. Fyb, Fya and Kell.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Influence of clinical status on the efficiency of stored platelet transfusion.

The efficiency of stored platelet transfusion was evaluated in terms of clinical status in 141 thrombocytopenic patients. In a paired prospective study in which fresh platelets were used as controls, clinical efficiency was assessed on the basis of the ability to increase platelet count (recovery) and the time to the next transfusion (D). In 48 clinically stable patients, recovery of fresh and stored platelets was similar (47% and 41%, respectively) and the interval to the next transfusion was D4 and D3. In contrast, 27 patients who had bacterial infections showed significantly different recoveries (24%/5%) and the interval to the next transfusion was D3/D1 for fresh and stored platelets respectively. Similarly, in 16 patients who were treated concurrently with amphotericin B, 18 other patients with graft-versus-host disease, nine with splenomegaly and four with veno-occlusive disease (VOD), fresh platelets performed better than stored platelets, showing recoveries of 27%/18%, 29%/15%, 16%/3% and 15%/2%. Furthermore, the need for retransfusion within 24 h was significantly increased with stored platelets. In 19 patients with anti-HLA alloimmunization who were transfused with HLA-matched fresh and stored apheresis platelet concentrate (APC), efficiency was similar (38%/36% and D4/D3). This study indicates that the storage induces an impressive decrease in the in-vivo platelet recovery and survival in patients with certain clinical conditions.

Adult↗
PubMed1994

Comparison of autografting using mobilized peripheral blood stem cells with and without granulocyte colony-stimulating factor in malignant lymphomas.

Peripheral blood is becoming widely used as the only source of hematopoietic stem cells to support marrow ablative therapy in advanced lymphoma. We report data from 23 patients with high risk non-Hodgkin's (n = 19) and Hodgkin's lymphoma (n = 4) who underwent high-dose therapy with mobilized peripheral blood stem cell (PBSC) autografting. Peripheral blood progenitors were recruited using cytotoxic chemotherapy followed by administration of recombinant human G-CSF (filgrastim 5 micrograms/kg/day). Myeloablative treatment with autologous PBSC support was administrated to the 23 patients and followed by G-CSF at the same dose after cell reinjection. Hematopoietic reconstitution was compared with a control group of lymphoma patients who received chemotherapy mobilized PBSC transplantation but without G-CSF prior to leukaphereses or after high-dose therapy. The median time to neutrophil recovery > 0.5 x 10(9)/l was significantly shorter in study patients compared with the control patients (10 days and 17 days respectively) (p < 0.05). Self sustaining platelet counts of > 50 x 10(9)/l occurred at a median time of 17 days in both groups. Stable hemopoietic reconstitution was seen with a follow-up of 6 months after PBSC transplantation. In addition, a significant relationship was observed between the number of CFU-GM infused and the time to platelet recovery. We confirm the effectiveness of G-CSF given prior to PBSC harvesting in generating high numbers of progenitor cells. Hematologic recovery following high-dose therapy was improved after PBSC rescue and G-CSF.

Adolescent↗
PubMed1993

Effect of human granulocyte colony stimulating factor on neuroblastoma cell growth.

We have studied the effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on the growth of three different human neuroblastoma (NB) cell lines, using a clonal cell culture and a short proliferation test. The results have shown a lack of effect of G-CSF on the three cell lines. These data promote the use, in clinical trials, of G-CSF as adjunctive treatment in children with NB receiving intensive chemotherapy.

Cell Division↗
PubMed1993

High-dose chemotherapy with etoposide, cyclophosphamide and escalating dose of carboplatin followed by autologous bone marrow transplantation in cancer patients. A pilot study.

25 patients with poor-prognosis malignancies were treated with a combination of fixed-dose etoposide (1750 mg/m2), cyclophosphamide (6400 mg/m2) and escalating doses of carboplatin (from 800 to 1600 mg/m2) followed by autologous bone marrow transplantation (ABMT). The median duration of granulocytopenia (< 500/mm3) and thrombocytopenia (< 20,000/mm3) was 23 days and 20.5 days, respectively. The main non-haematological toxicity was gastro-intestinal, with moderate to severe diarrhoea in 15 patients. No significant renal toxicity was observed. 2 patients died early due to toxicity. The overall response rate was 58% including 42% having complete responses. 4 of the 25 patients are alive with no evidence of disease at 22, 27, 40 and 43 months after ABMT. The encouraging antitumoral activity of this regimen makes it a good candidate for intensified chemotherapy in patients with various malignancies. Toxicity is acceptable and may be reduced in the near future with the widespread use of haematopoietic growth factors.

Adolescent↗
PubMed1993

[Influence of clinical status on the efficacy of stored platelet transfusion].

The efficiency of stored platelet transfusion was evaluated in terms of clinical status in 136 thrombocytopenic patients. In a paired prospective study in which fresh platelets were used as controls, clinical efficiency was assessed on the basis of the ability to increase platelet count (recovery) and the interval to the next transfusion (D). In 48 clinically stable patients, recovery of fresh and stored platelets was similar (47% and 41% respectively) and the interval to the next transfusion was D4 and D3. In contrast, 27 patients who had bacterial infections showed significantly different recoveries (24%/5%) and the interval to the next transfusion was D3/D1 for fresh and stored platelets respectively. Similarly, in 16 patients who were treated concurrently with Amphotericin B, 18 other patients with graft-versus-host disease, 5 with splenomegaly and 3 with veno-occlusive disease (VOD), fresh platelets performed better than stored platelets, showing recoveries of 27%/18%, 29%/15%, 15%/1%, 22%/3%. Furthermore, the need for retransfusion within 24 hours was significantly increased with stored platelets. In 19 patients with anti-HLA allo-immunization who were transfused with HLA-matched fresh and stored APC, efficiency was similar (38%/36% and D4/D3). This study indicates that the storage has a major detrimental effect on platelet recovery and survival in patients with certain clinical conditions.

Adolescent↗
PubMed1993

Frozen blood and transfusion-transmitted hepatitis C virus.

The purpose of the present study was to evaluate the impact of frozen red cell transfusion on the transmission of hepatitis C virus (HCV) before the introduction of blood donor screening. Anti-HCV antibodies were detected in 59 patients with sickle-cell disease who required chronic transfusions and had exclusively received frozen red blood cells (RBC). The files were reviewed for clinical signs of chronic hepatitis C. Anti-HCV antibodies were detected in 2 adult patients; both also had clinical evidence of HCV infection. No other patient showed signs of acute or chronic HCV hepatitis. In a control group of 28 patients who had received nonfrozen RBC transfusions, the prevalence of anti-HCV antibodies was 25%. So, our study seems to indicate that the use of frozen RBC had reduced the risk of HCV contamination.

Adolescent↗