PubMed Health⌕ Search

Biomedical subjects

F Isnard

Publications and source records attributed to F Isnard.

At least 19 recordsLinked to original sources
PubMed2006

Imatinib and methylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALL AFR09 study.

Acute lymphoblastic leukemia (ALL) in the elderly is characterized by its ominous prognosis. On the other hand, imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), which prompted us to assess the use of imatinib in previously untreated elderly patients. ALL patients aged 55 years or older were given steroids during 1 week. Ph+ve cases were then offered a chemotherapy-based induction followed by a consolidation phase with imatinib and steroids during 2 months. Patients in complete response (CR) after consolidation were given 10 maintenance blocks of alternating chemotherapy, including two additional 2-month blocks of imatinib. Thirty patients were included in this study and are compared with 21 historical controls. Out of 29 assessable patients, 21 (72%, confidence interval (CI): 53-87%) were in CR after induction chemotherapy vs 6/21 (29%, CI: 11-52%) in controls (P=0.003). Five additional CRs were obtained after salvage with imatinib and four after salvage with additional chemotherapy in the control group. Overall survival (OS) is 66% at 1 year vs 43% in the control group (P=0.005). The 1-year relapse-free survival is 58 vs 11% (P=0.0003). The use of imatinib in elderly patients with Ph+ ALL is very likely to improve outcome, including OS.

Aged↗
PubMed2004

A long-term follow-up of 33 patients with non-Hodgkin's lymphoma who received the BEAM high-dose intensification regimen with cytokine support only and no transplant.

High-dose intensification and autologous stem-cell transplantation (ASCT) is widely used to consolidate patients with non-Hodgkin's lymphoma (NHL), who have reached a stage of minimal residual disease. However, patients with persisting marrow and/or blood involvement and those who fail peripheral blood hemopoietic progenitor mobilization are excluded from ASCT. For such patients with no available graft to infuse, we developed 15 years ago, before the anti-CD20 monoclonal antibody therapeutic era, the use of the BEAM pretransplant regimen followed only by the administration of three cytokines (erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor). We report here on the long-term follow-up of 33 patients treated with this approach. In all, 33 NHL patients underwent the BEAM (carmustine, VP-16, cytosine-arabinoside, melphalan) followed by the administration of the three cytokines from January 1994-2000. A backup marrow, albeit infiltrated by tumor cells, had been collected earlier and stored in all. A total of 30 patients (91%) recovered normal hematopoiesis. In total, 32 patients (97%) recovered neutrophils (>500/microl) at a median of 19 days and 30 patients (91%) recovered platelets (>20,000/microl) at a median of 26 days. Age, richness of backup graft and blood-hemoglobin level at intensification had an impact on the time for hematopoietic recovery (P=0.014, P=0.014, P=0.048). The median follow-up was 62 months. Five patients died from toxicity related to the procedure. Eight patients relapsed and died. A total of 20 patients (61%) are alive, 16 (49%) in complete remission. A 5-year disease-free survival was 52+/-9%, relapse incidence 35+/-16%, mortality due to the procedure 12+/-12% and overall survival 61+/-10%. The BEAM regimen is not myeloablative. The BEAM+3CK procedure is a feasible therapeutic option that has shown efficacy in poor risk NHL patients who were not eligible for autografting because of persisting marrow/blood tumor contamination, or poor hemopoietic progenitor harvesting. It is unclear today whether some of these patients would have cleared their marrow/peripheral blood with the additional use of anti-CD20 treatment, thereby making the classical approach (BEAM followed by the infusion of a clean autograft) feasible.

Adult↗
PubMed2001

[Vascular complications of diabetes: is there a glycemic threshold?].

A causal relation is established between hyperglycaemia and cardiovascular disease, but is there a glucose threshold for diabetic macroangiopathy comparable to the fasting glucose concentration of 7 mmol (126 mg)/dL for diabetic microangiopathy? The diagnostic criteria for diabetes are now based on this relation. Data from long-term prospective have been convergent in showing the lack of a glucose threshold for diabetic macroangiopathy: mortality is a progressive and continuous function of glucose concentrations and also fo glycated haemoglobin levels. This observation highlights the necessity for optimal glycaemic control as well as treatment of other risk factors to prevent vascular complications of diabetes mellitus.

Adult↗
PubMed2001

Improved efficiency of remission induction facilitates autologous BMT harvesting and improves overall survival in adults with AML: 108 patients treated at a single institution.

A hundred and eight patients less than 60 years old with de novo acute myeloid leukemia were treated between 1982 and 1994 by protocols including final intensification with a transplant using autologous bone marrow purged by mafosfamide in first remission in the absence of an HLA-matched sibling donor available for allograft. From 1989, we attempted to improve tumor control by using high-dose anthracyclines in induction, by increasing from one to two the number of consolidation courses pre-transplant and by introducing intermediate doses of cytarabine in the first consolidation course. The CR rate was 77% (33/43) before 1989 and 90% (59/65) after 1989 (P = 0.06). Forty-five out of the 59 patients (76%) who achieved CR after 1989 could undergo bone marrow grafting in CR1 vs 16/33 (48%) before 1989 (P = 0.01). In spite of the higher proportion of patients above 50 years after 1989 (32%) toxicity was mild and an adequate graft was obtained more frequently after one collection. The principal factor relating to improvement in graft feasibility was the post-1989 modification of induction and consolidation regimens. This improvement in graft feasibility was associated with a better disease-free survival (DFS) (48 +/- 7% vs 32 +/- 8%, P = 0.04) and overall survival (OS) (53 +/- 6% vs 30 +/- 7%, P = 0.007) at 5 years. By multivariate analysis four factors were associated with overall survival (OS): karyotype, white blood cell count at diagnosis, treatment regimen and bone marrow grafting in CR1. This global approach should be prospectively compared with intensive chemotherapy.

Acute Disease↗
PubMed2001

Acute liver failure as initial manifestation of low-grade non-Hodgkin's lymphoma transformation into large-cell lymphoma.

Acute liver failure as an initial manifestation of primary non-Hodgkin's lymphoma is a rare phenomenon with a grim prognosis. We report for the first time on a patient with a history of follicular lymphoma in complete remission, presenting fulminant liver failure due to massive liver infiltration by transformed lymphoma cells and portal vein thrombosis, as an initial manifestation of transformation into large-cell lymphoma.

Abdominal Pain↗
PubMed1999

[Comparison of infectious complications of long-term and short-term central venous catheterization].

OBJECTIVES: Risk factors for infectious complications of central venous catheters (CVC) were compared between CVC used for short and long periods to identify patients at risk. PATIENTS AND METHODS: A prospective study was conducted over a 6 month period in two general intensive care units (87 patients with short duration CVC) and in 4 medical units (110 patients with cancer or HIV infection for whom long duration CVC was scheduled). The first CVC inserted was followed to withdrawal or for a minimal 3 months. RESULTS: The mean duration of CVC use was 7.5 and 106 days for the short and long duration groups respectively. A CVC-related infection occurred in 6 patients in the short duration group and in 14 patients in the long duration group giving an incidence of 1.0/100 CVC days (95% CI: 0.4-2.0) for the short-duration CVC group and 0.13/100 CVC days (95% CI: 0.07-0.21) for the long-duration CVC group. Intensive care patients with a skin lesion far from the CVC insertion point had a higher incidence of CVC-related infection than patients without a skin infection. Taking into account the indications for CVC, patients with cancer or HIV infection had equivalent risk of infection. For both short and long duration CVC use, parenteral nutrition was found to be a major risk factor for infectious complications. CONCLUSION: Rigorous regular surveillance of nosocomial infections on central catheters should be centered on those inserted for parenteral nutrition.

Aged↗
PubMed1999

Importance of marrow dose on posttransplant outcome in acute leukemia: models derived from patients autografted with mafosfamide-purged marrow at a single institution.

Several prospective randomized trials in acute myelocytic leukemia (AML) documented a lower relapse rate with autologous bone marrow transplantation (ABMT) than with conventional chemotherapy. However, they also identified some transplant difficulties, such as failure to collect sufficient numbers of stem cells, slow kinetics of engraftment, and a high transplant-related mortality that diminished or negated positive impact on overall survival. Data for ABMT are inconclusive in acute lymphocytic leukemia (ALL) in adults. We retrospectively analyzed patients with acute leukemia autografted with marrow purged with mafosfamide after January 1983 in our institution. The population comprised 229 consecutive patients; 165 with AML [123 in first remission (CR1), 32 in second remission (CR2)]; 61 with ALL (46 in CR1, 4 in CR2); and 3 with undifferentiated acute leukemia. All patients were autografted with marrow purged with mafosfamide. Mafosfamide was given at a constant dose of 50 microg/mL in 103 and adjusted individually to produce a CFU-GM LD 95 (5% residual CFU-GM post purging) in 126. The outcome was analyzed for correlation with patient characteristics, the disease including cytogenetics, and the graft itself. Prognostic factors identified by multivariate analysis were used to derive a prognostic classification. Patients receiving higher doses of marrow submitted to purging (>5.46 x 10(4) CFU-GM/kg) experienced a lower treatment-related mortality (RR = 0.11, p = 0.005) and a higher leukemia-free (RR = 0.5, p = 0.005) and overall survival (RR = 0.4, p = 0.001). Patients receiving <0.004% CFU-GM of marrow actually infused post purging had a lower relapse rate (RR = 0.51, p = 0.003). Modeling of prognostic groups identified good-, intermediate-, and poor-risk categories. Patients receiving a stem cell dose evaluated before purging of >5.46 x 10(4) CFU-GM/kg and doses actually infused post purging of < or =0.02 x 10(4)/kg had a treatment-related mortality of only 2+/-2%, a leukemia-free survival of 70%, and an overall survival of 77+/-7% at 10 years. In this study of autotransplantation for acute leukemia using mafosfamide-purged marrow, the stem cell dose used for purging and the intensity of purging were the most important factors predicting outcome.

Adolescent↗
PubMed1999

Progressive multifocal leucoencephalopathy with peripheral demyelinating neuropathy after autologous bone marrow transplantation for acute myeloblastic leukemia (FAB5).

Progressive multifocal leucoencephalopathy is an opportunistic JC virus-related pathology occurring in immunocompromised patients. We report a case of severe cellular immunodeficiency in a patient who underwent autologous bone marrow transplantation for acute myeloblastic leukemia, and who subsequently developed progressive multifocal leucoencephalopathy, an unusual pathology in this context. Progressive multifocal leucoencephalopathy was preceded by a peripheral demyelinating neuropathy. We discuss the possible link between these two neuropathies, the possible aggravation or activation from CMV infection, as well as the possible contribution of bone marrow purging in the resultant cellular immunodeficiency.

Adult↗
PubMed1998

Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases.

We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients with abnormal karyotypes. Most karyotypes were complex with numerical and structural abnormalities but the analysis of chromosomal abnormalities allowed identification of two cytogenetic patterns depending on the chromosome number: a first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and 19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near-tetraploid karyotypes. Structural abnormalities were present in all but five hyperdiploid karyotypes, and frequently involved lymphoid breakpoints: immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases). Numerous other structural aberrations were detected; the most frequent involved chromosome 1 and chromosome 13. Structural abnormalities were significantly more frequent in the second hypodiploid group. When analyzing the results obtained in the 60 patients studied at the time of diagnosis, a prognostic correlation was found between the cytogenetic pattern and overall survival: hyperdiploid patients had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid group (median survival 36.8 vs 18.2 months, P < 0.04). These results suggest that MM could correspond to two closely related diseases.

Adult↗
PubMed1998

Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation--results of a retrospective analysis on 120 patients autografted in a single institution.

PURPOSE: To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution. PATIENTS AND METHODS: A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement. RESULTS: Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS. CONCLUSION: This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.

Adult↗
PubMed1997

Bone marrow versus peripheral blood progenitor cells CD34 selection in patients with non-Hodgkin's lymphomas: different levels of tumor cell reduction. Implications for autografting.

Human CD34+ selected cells are able to reconstitute hematopoiesis in patients receiving a myeloablative treatment. Although the role of reinfused tumor cells contaminating the grafts on the determination of postautograft relapses remains unclear, the major interest of CD34+ cell selection is to reduce the tumor contamination of the graft. This can be achieved if tumor cells do not express the CD34 antigen. We previously showed that this approach was effective with bone marrow (BM) collections in patients with non-Hodgkin's lymphoma (NHL). Because peripheral blood progenitor cells (PBPC) allow faster hematologic recovery than BM and are expected to contain less tumor contamination, we have compared the results of CD34+ cell selection in 35 BM and 16 PBPC from 48 patients with NHL. The PBPC were collected after a course of chemotherapy followed by granulocyte colony-stimulating factor (G-CSF) administration. The data showed that the final CD34+ cell purity achieved with PBPC was higher than with BM (medians, 70% v 50%; P = .02). The CD34+ cell recovery was also better for PBPC (medians, 42% v 24%; P = .001). Tumor contamination was assessed by detection of BCL2/JH rearrangement using polymerase chain reaction (PCR) in 38 of 48 patients (22 BM, 16 PBPC). In addition, immunoglobulin heavy chain gene (IgH) rearrangements were investigated using PCR with consensus IgH primers. At harvesting, 10 of 22 BM and two of 16 PBPC contained BCL2/JH+ cells, one of 22 BM and 14 of 16 PBPC contained abnormal IgH+ cells (one PBPC contained both BCL2/JH+ and abnormal IgH+ cells) at harvesting. However, because lymphoma tissue specimens from patients at diagnosis were not available, the malignant character of IgH rearrangements could not be confirmed by sequencing and probing with allele-specific nucleotides. After CD34+ cell selection, a reduction to below the level of detection of BCL2/JH+ cells of BM and PBPC was effective in seven of 12 informative selections. In contrast, a reduction to below the level of detection of abnormal IgH+ cells was effective in only three of 15 informative selections. However, the detection of cells with an abnormal IgH pattern in the context of chemotherapy plus G-CSF progenitor mobilization in patients with NHL and its correlation with actual tumor contamination needs further investigation.

Adult↗
PubMed1997

[Central venous catheters. Prospective surveillance of a hospital].

OBJECTIVES: All the central venous catheters (CVC) inserted at the Saint-Antoine Hospital between December 5, 1994 and June 6, 1995 were prospectively studied in order to better define practices in the management of CVC and to determine the rate of catheter-related infections. METHODS: The following data were recorded for each CVC: insertion procedure, clinical data, catheter dressings, removal, catheter-related infections, bacteriological findings. Catheter-related infections were distinguished from probably catheter-related infections and localized skin infections. RESULTS: Among 325 patients, a total of 414 catheters were inserted. At the end of the surveillance period, 350 (85%) had been removed, 43 (10%) were still in place and 21 (5%) were lost to follow-up. Analysis of procedures such as cutaneous disinfection, routine replacement of the i.v. sets or changes of dressings showed wide variations between care units and within the same unit. The overall incidence of catheter-related infections was 0.24 per 100 days of catheterization. Infections occurred 29 +/- 34 days after insertion. Microorganisms responsible for catheter-related bacteremia were mostly Gram positive (84%) and Gram negative (16%). Sixty-two infections (15%) were clinically suspected by physicians, leading to the catheter removal in 84% of cases. Out of the 43 CVC sent to the laboratory, 29 (67%) were negative (i.e., "sterile") in quantitative culture of the tips as described by Brun-Buisson, suggesting that the CVC was unnecessarily removed. Bacteriological analysis ordered by physicians were not always relevant. For example, 76% of CVC received by the laboratory were systematically sent although they were not suspected of infections. Conversely, only 61% of exsudate formation at the insertion site were collected and analyzed. CONCLUSION: This study was designed to recall good guidelines to the hospital staff. Results will lead to the development of a better use of antiseptics and to the implementation of appropriate and standardized procedures to reduce risk infection.

Adult↗
PubMed1997

Plasma itraconazole concentrations in patients with neutropenia: advantages of a divided daily dosage regimen.

A group of 36 patients in the hematology department of Saint-Antoine Hospital, Paris, France, was on chemotherapy. The patients were also given antiacid drugs to prevent gastrointestinal toxicity and itraconazole as prophylaxis against aspergillosis. The antifungal drug was given as 100-mg capsules three times a day shortly after meals. The plasma itraconazole and hydroxyitraconazole concentrations were measured by high-performance liquid chromatography at steady state. Of 36 patients, 29 (81%) had adequate plasma itraconazole concentrations (> or = 250 ng/ml) after 8 +/- 2 days. The 7 patients with low plasma itraconazole concentrations were given 200 mg three times a day. Of the 36 patients, 34 (94%) had effective plasma concentrations within 2 weeks of the beginning of treatment. The two remaining patients were lost to follow-up. The proposed itraconazole regimen provides effective prophylaxis against aspergillosis and represents a substantial economic advantage over a single daily dose of 400 to 600 mg. The marked intrapatient and interpatient variations in plasma itraconazole indicate the need for regular therapeutic drug monitoring to ensure effective plasma itraconazole concentrations in all neutropenic patients.

Adolescent↗