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F Isnard

Publications and source records attributed to F Isnard.

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

Comparison of the effects of AcSDKP, thymosin beta4, macrophage inflammatory protein 1alpha and transforming growth factor beta on human leukemic cells.

We have compared the effects of AcSDKP, Thymosin beta4 (Tbeta4), MIP1alpha and TGFbeta on acute myeloid leukemia (AML) and B-lineage acute lymphoid leukemia (B-ALL) cells using liquid cultures in the presence of GM-CSF, IL-3 and SCF for AML cells and IL-3 and IL-7 for ALL cells. Each molecule was added daily and cell proliferation was evaluated on day 3 by thymidine incorporation. Whereas TGFbeta was found inhibitory in all the AML and B-ALL cases studied, MIP1alpha was inhibitory in 6/12 AML cases and had no effect on B-ALL cells. AcSDKP and Tbeta4 showed an inhibitory effect in a few cases but only at high doses which were inactive on normal cells. Thus, our study not only confirms the effect of TGFbeta, MIP1alpha and AcSDKP on AML cells but also provides new data concerning their effect on B-ALL and the possible inhibitory effect of AcSDKP at high doses. Furthermore, we show for the first time the effect of Tbeta4 on leukemic cells. Altogether, our data indicate differences of sensitivity of leukemic cells to negative regulators, some leukemias being inhibited by one or several of these molecules whereas others were unresponsive to all used. The clinical relevance of these observations still remains to be determined.

Adolescent↗
PubMed1996

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

Adipose Tissue↗
PubMed1996

Autologous bone marrow transplantation is feasible in patients with a prior history of invasive pulmonary aspergillosis.

We report on seven adult leukemic patients who were autografted in spite of a prior history of invasive pulmonary aspergillosis (IPA). Their median age was 41 years (range: 19-61); six patients were male and one female. All seven had acute myeloblastic leukemia (AML) and underwent an autologous marrow transplantation (ABMT) with a marrow purged in vitro by mafosfamide. IPA was suspected prior to ABMT on clinical and radiological features. CT scan confirmed nodular infiltrates and cavitations in six cases. Microbiological documentation consisted of: identification of the fungus from bronchoalveolar lavage: one case, positive antigenemia: one case, positive antibodies: two cases. Prior ABMT patients received amphotericin B for a median total dose of 1915 mg (range: 970-3300). No patient underwent surgery. The median time from diagnosis of IPA to ABMT was 7.3 months (range: 3-10). During ABMT all patients received prophylactic amphotericin B and itraconazole. No patient died from toxicity and no IPA reactivation was observed in any patients. Post-graft, itraconazole was kept on for a median of 3 months (range: 3-5). This study demonstrates that IPA occurring during the management of AML patients is not necessarily a contraindication to subsequent ABMT.

Acute Disease↗
PubMed1995

Preparation and successful engraftment of purified CD34+ bone marrow progenitor cells in patients with non-Hodgkin's lymphoma.

From September 1992 to January 1994, we evaluated the use of the CEPRATE SC stem cell concentrator (CellPro, Inc, Bothell, WA) to select CD34+ cells from the bone marrow (BM) of 25 patients with non-Hodgkin's lymphoma in complete remission. This system uses the biotinylated 12.8 IgM MoAb to select CD34+ cells. Cells are retained on an avidin column and detached by agitation. Fifteen patients have been transplanted with the CD34+ purified fraction. The CD34+ purified fraction of the 25 processed BMs contained a median of 0.54% of the original nucleated cells in a volume of 5 to 10 mL. The median concentration of CD34+ cells was 49% (range, 12% to 80%), and the median enrichment of CD34+ cells was 33-fold (range, 9- to 85-fold). This selected CD34+ fraction retained 60% (range, 15% to 95%) of late granulocyte-macrophage colony-forming units (CFU-GM), 55% (range, 12% to 99%) of early CFU-GM, and 31% (range, 2% to 100%) erythroid burst-forming units (BFU-E) corresponding to median enrichments of 22-fold (range, 1- to 71-fold), 19-fold (range, 2- to 58-fold), and 14-fold (range, 2- to 200-fold), respectively. There was a correlation between immune phenotypes and progenitor cells. In the initial buffy-coat fractions, the percentage of CD34+ cells was correlated to the cloning efficiency of both late CFU-GM (P < .05) and early CFU-GM (P < .001). In the final selected fraction, there was a correlation between the percentage of CD34+/CD33- and the cloning efficiency of early CFU-GM (P < .05) and between the percentage of CD34+/CD33+ and the cloning efficiency of late CFU-GM (P < .05). Lymphoma cells positive for t(14; 18) were found by polymerase chain reaction in 9 of 14 buffy coats tested before CD34+ cell purification. In 8 cases, the CD34(+)-selected fraction was found to be negative, and the CD34- fraction was found to be positive. After cryopreservation, the recoveries of progenitor cells in the CD34(+)-purified fraction were 79% for late CFU-GM, 71% for early CFU-GM, and 73% for BFU-E. The 15 patients transplanted with the concentrated CD34+ fraction received a median dose of 1 x 10(6) CD34+ cells/kg (range, 0.3 to 2.96) and 10.62 x 10(4) early CFU-GM/kg (range, 0.92 to 25.55). Median days to recovery to 0.5 x 10(9)/L neutrophils and 50 x 10(9)/L platelets were days 15 (range, 10 to 33) and 23 (range, 11 to 68), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Cytogenetic study in multiple myeloma at diagnosis: comparison of two techniques.

Cytogenetic studies in multiple myeloma (MM) have been disappointing due to the low mitotic index of plasma cells. Recently the detection of clonal chromosomal abnormalities at diagnosis seemed to be improved by addition of cytokines (IL-6 and GM-CSF) in the culture medium. We performed two parallel total bone marrow cells culture types in 33 stage I, II and III multiple myeloma patients at diagnosis: 3 d without any cytokine, and 4-7 days stimulated with IL-6 and GM-CSF. No clonal chromosomal abnormality was detected in the 12 stage I and II patients either in 3 d or in 4-7 d culture. In stage II patients, abnormalities were observed in 18/21 (85.7%) and in 8/18 (44.4%) in the 3 d culture and the 4-7 d stimulated cultures respectively. Our results suggest that in stage III multiple myeloma at diagnosis, 3 d culture without cytokine may be the better technique to detect clonal chromosomal abnormalities, and, before using cytokines as a reference condition, this 3 d unstimulated culture should be considered.

Aged↗
PubMed1995

Treatment of Waldenstrom's macroglobulinemia with very low doses of alpha interferon.

Waldenström's macroglobulinemia (WM) is a differentiated B-cell malignancy which is usually less responsive to standard chemotherapy because of low-proliferating cells. Interferon alpha has been shown to possess a therapeutic action in numerous B-cell malignancies including the early stage of chronic lymphocytic leukemia, multiple myeloma, follicular lymphoma and hairy cell leukemia. Fourteen patients with progressive WM were included in a pilot study using very low dose of interferon alpha-2a (1 Million Units 3 times a week). The mean duration of treatment was 10.3 months (range 2-44). Six of 14 (42%) patients presented an increase in the hemoglobin level (> or = 0.9 g/dL) and 4/14 (28%) had a substantial decrease of the monoclonal component (> or = 20% of reduction). Only two patients presented both types of response, while the others with an increase in the hemoglobin level had a slight decrease in the monoclonal component (MC) (1 patient), a stable MC (1 patient) or a slight increase of MC (1 patient). One additional patient had a 15% decrease of the MC with a stable hemoglobin level. Response was observed within 3 months with a median duration of 6 months. Treatment was stopped for 3 patients because of flu-like symptoms (2 patients), or thrombocytopenia (1 patient). Follow up was possible in 12 patients lasting up to a maximum of 30 months after discontinuing treatment. Seven patients died, including 4 with progressive disease, two of infection and one of cardiac failure. In the view of these results, very low dose of interferon alpha may constitute a new approach for treatment of some cases of WM.

Aged↗
PubMed1995

Autologous bone marrow transplantation as consolidation therapy may prolong remission in newly diagnosed high-risk follicular lymphoma: a pilot study of 34 cases.

We evaluated early intensification followed by autologous bone marrow transplantation (ABMT) using marrow purged by mafosfamide in patients with high-risk low-grade follicular lymphoma (LGFL) reaching a status of minimal disease (MD). Thirty-four patients entered the program. All fulfilled at least one of the following criteria at diagnosis: a bulky tumor > 7 cm; three or more adenopathies > 3 cm; massive pleural or peritoneal effusion; massive splenomegaly; B symptoms; platelet count < 100 x 10(9)/l. Twenty-one patients had bone marrow involvement. Twenty-six patients received ACVBP, and eight CVP as front-line therapy. Twenty-one (62%) patients achieved MD status, 18 reached intensification. At 4 years, the time to treatment failure is 55 +/- 9%, and the probability of persisting remission is 75 +/- 11%. Comparison by intention to treat of the 26 patients who received ACVBP as front-line therapy to 14 historical high-risk LGFL similarly treated in our institution without intensification, showed better results for the intensified group (P = 0.04 for both probability of persisting remission and time to treatment failure). These results indicate that early intensification using marrow purged with mafosfamide is a therapeutic option which may bring benefit to patients with high-risk LGFL.

Adult↗
PubMed1994

One hundred twenty-five adult patients with primary acute leukemia autografted with marrow purged by mafosfamide: a 10-year single institution experience.

A total of 125 acute leukemia adult patients were autografted with bone marrow (BM) purged by mafosfamide (ASTA Z) during the period of January 1983 to January 1993. The median follow-up period was 64 months (range, 3 to 126). There were 84 acute myeloblastic leukemias (AMLs) and 41 acute lymphoblastic leukemias (ALLs). At time of autologous BM transplantation (ABMT); 64 AMLs were in first complete remission (CR1), and 20 were in second CR (CR2); 35 ALL were in CR1, and 6 were in CR2. The median age of the patients was 33 years (range, 16 to 55). The median interval between achieving CR and autografting was 5 months (range, 1.3 to 23). The pretransplant regimen consisted of cyclophosphamide (120 mg/kg) and total body irradiation. All patients were grafted with autologous BM treated in vitro with mafosfamide used at levels individually adjusted in 95 patients and at a standard dose in 30 patients. The initial richness in granulomacrophagic progenitors (CFU-GM) of the harvested BMs was 5.16 x 10(4) CFU-GM/kg (range, 0.55 to 33). After mafosfamide purging, the residual CFU-GM number was 0.021 x 10(4)/kg (range, 0 to 1.78). The probability of successful engraftment was significantly higher and the time to engraftment was significantly shorter in ALL. Of 33 patients grafted with BM containing no residual CFU-GM, those with AML (n = 22) had platelet recoveries that were significantly longer than those for AML patients receiving BM with residual CFU-GM. At 8 years, patients autografted in CR1 for AML and ALL had a leukemia-free survival (LFS) of 58% and 56%, respectively, with a relapse incidence (RI) of 25% and 37%, respectively. Patients autografted in CR2 for AML had an LFS of 34% and an RI of 48% at 5 years. The incidence of late relapses was significantly higher in ALLs. By multivariate analysis, four factors were found to influence favorably engraftment in addition to a diagnosis of ALL, a younger age, ABMT performed in CR1, the adjusted dose technique of purging, and a shorter interval from CR to ABMT. Two factors were correlated with a better outcome. (1) The LFS was significantly higher and the transplant-related mortality significantly lower in patients who received richer BM. (2) The RI was significantly lower in patients autografted within 150 days from CR. Our results reinforce the view that ABMT is one approach to improve the outcome of adult patients with acute leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Efficacy of recombinant human erythropoietin in the treatment of refractory anemias without excess of blasts in myelodysplastic syndromes.

To determine the efficacy of recombinant human erythropoietin at pharmacological doses in myelodysplastic syndromes (MDS) without excess of blasts, 20 patients with refractory anemias (RA) or refractory anemias with ring sideroblasts (RARS) were treated in an open study with escalating doses from 40 U/kg to 300 U/kg three times a week subcutaneously during a period of 3 months. Maintenance therapy at the lowest effective dose was continued in responders. A dose response of CFU-E and BFU-E to Epo was analysed at the entry. Bone marrow examination with an in vitro study of hematopoietic progenitors was performed before and after the first three months. Seven of 20 patients responded: a total recovery was observed in 3 patients; one became transfusion independent and a reduction of 50% of the transfusion requirement was achieved in 3 others. 3 patients are still receiving treatment for 2, 3 and 4 years. No significant correlation was found between the in vitro and clinical response. A non parametric analysis of responders and non responders emphasised the importance of a long delay between the diagnosis and the treatment, (p = 0.024) and an endogenous Epo level less than 100 mU/ml (p = 0.025) in order to predict the efficacy of rhEpo. This study offers evidence that patients with refractory anemias without excess of blasts in the bone marrow respond to rhEpo at pharmacological doses. Larger studies are required in order to define the patients who may respond and to elucidate the mechanism of the positive effect of rhEpo.

Adult↗
PubMed1994

In vivo effects of GM-CSF and IL-3 on hematopoietic cell recovery in bone marrow and blood after autologous transplantation with mafosfamide-purged marrow in lymphoid malignancies.

This retrospective study evaluates the impact of GM-CSF and interleukin 3 (IL-3) on bone marrow (BM) and peripheral blood (PB) cell recovery following autologous bone marrow transplantation (ABMT) with mafosfamide-purged BM in patients with lymphoid malignancies compared with a control group receiving no colony-stimulating factor. GM-CSF was administered at 250 micrograms/m2/day (8 patients) as a continuous infusion from day of autologous BMT until the absolute neutrophil count (ANC) reached 0.5 x 10(9)/l for 7 days or until day 30, whichever was first. IL-3 was administered daily starting on the first day of transplant at a dose of 1 microgram/kg/day (6 patients) and 5 micrograms/kg/day (6 patients) for 30 days. CFU-GM and BFU-E were sequentially evaluated in BM and PB at days 7, 14, 21, 28, and 56 post-graft. The neutrophil recovery (ANC > 0.5 x 10(9)/l) was significantly faster in the GM-CSF group compared with IL-3 5 micrograms, IL-3 1 microgram and control group (respectively, days 15, 21, 22, 24) (p < 0.05 to p < 0.01). Similarly, leukocyte recovery was faster in the GM-CSF group compared with control and IL-3 1 microgram groups (p < 0.01 and p < 0.05). No difference was noticed between the two IL-3 groups. Although no difference was observed in platelet recoveries (> 50 x 10(9)/l), it appeared that the GM-CSF group required more units of platelets than either the IL-3 1 microgram or 5 micrograms groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Autologous bone marrow transplantation in ALL: relapse linked to infusion of tumor cells with the back-up marrow.

A 41-year-old female patient with a pre-B ALL expressing 2 BCR/ABL transcripts e1/a2 and b2/a2 underwent autologous bone marrow transplantation (aBMT) with marrow grown in long-term culture (LTC) for consolidation of remission (CR). After failing to engraft on day 54 she received her back-up marrow. She engrafted by day 23 and developed a full-blown leukemic relapse 2 weeks later. She died from tumor progression 3 months after infusion of the backup marrow. Analysis of the BCR/ABL transcripts weakly positive at time of collection of the backup marrow, negative in the LTC marrow and in the patient after infusion of the LTC marrow, again positive from day 29 after infusion of the backup marrow until death, strongly suggests that infusion of residual tumor cells with the backup marrow contributed to the relapse.

Adult↗
PubMed1993

[Positive selection of hematopoietic CD 34 stem cells for autograft].

The CD 34 antigen is a glycoprotein found on the surface of hematopoietic stem cells and early committed progenitors. The CE 34 stem cells from 14 samples of bone marrow, cord blood or leucapheresis were isolated using a positive selection procedure involving an anti CD 34 biotinylated monoclonal antibody and an avidin immunoabsorption device. Results showed that in 60 percent of samples, the positively-selected fractions contained more than 70 percent CD 34 cells. Concentration in CFU-GM and BFU-E progenitors increased 15 and 26 fold respectively in the CE 34 enriched samples. Long-term culture of two samples demonstrated that nearly all of the most immature progenitors were recovered in the procedure. These preliminary results showed that the positive selection technique of CD 34 hematopoietic stem cells is now available for use in autologous or allogeneic hematopoietic stem cell transplantation.

Antigens, CD↗
PubMed1993

Autologous bone marrow transplantation with marrow purged by mafosfamide in seven patients with myelodysplastic syndromes in transformation (AML-MDS): a pilot study.

Seven patients with acute myeloblastic leukemia (AML) occurring on myelodysplastic syndromes (MDS) were consolidated while in complete remission (CR) by autologous bone marrow transplantation (ABMT) with a marrow purged in vitro by mafosfamide. The median age of population was 44 years (range 39-55). MDS FAB diagnosis was established before progression to AML in five patients: refractory anaemia with excess of blast (RAEB) in three patients, RAEB in transformation (RAEB-t) in one patient, and chronic myelomonocytic leukemia (CMML) in one patient. In the remaining two patients, the diagnosis of MDS (as a secondary malignancy in one) was made retrospectively at time of overt AML. Three out the seven patients had karyotypic abnormalities. The median interval between the obtention of CR and ABMT was 7 months (range 6-18). One patient died from transplant related toxicity. Engraftment occurred at a median of 41 days (range 27-60), for white blood cells (> 10(9)/l) and 120 days (range 60-180) for platelets (> 50 x 10(9)/l). Four patients relapsed at 2.5, 6.8, and 25 months post-ABMT. Two patients are alive and well at 10 and 28 months, respectively. ABMT with marrow purged by mafosfamide is feasible in patients with AML following MDS with a prospect of cure. However, further studies are needed to assess the real value of this approach.

Adult↗