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F Guilhot

Publications and source records attributed to F Guilhot.

At least 19 recordsLinked to original sources
PubMed2000

Persistence of BCR-ABL genomic rearrangement in chronic myeloid leukemia patients in complete and sustained cytogenetic remission after interferon-alpha therapy or allogeneic bone marrow transplantation.

In recent years, the prognosis of chronic myeloid leukemia (CML) has been greatly improved either with interferon-alpha (IFN-alpha) therapy or allogeneic bone marrow transplantation (BMT). In the present study, minimal residual disease was evaluated in 21 patients in complete cytogenetic response (CCR) after such treatments. Samples from bone marrow aspirates or peripheral blood or both were analyzed by conventional cytogenetics, Southern blot, interphase fluorescent in situ hybridization (FISH), and quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR). In all patients, FISH detected 1% to 12% nuclei with a BCR-ABL fusion gene, whereas Q-RT-PCR experiments were negative or weakly positive. Based on these results, we hypothesize that the BCR-ABL genomic rearrangement persists unexpressed in nonproliferating cells whatever the treatment (IFN-alpha or BMT). These data point to the need for follow-up of CML patients in CCR over an extensive period at the DNA level (FISH) to evaluate the residual disease and at the RNA level (Q-RT-PCR) to estimate the risk of relapse. (Blood. 2000;95:404-408)

Adult↗
PubMed2000

Thrombotic thrombocytopenic purpura during interferon alpha treatment for chronic myelogenous leukemia.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome have recently been observed in patients undergoing interferon alpha (IFN-alpha) therapy. However, the relationship between disease and therapy has not been established, essentially because of concomitant treatment or previous bone marrow transplantation. We present a case of TTP developing during IFN-alpha therapy for chronic myelogenous leukemia. In this case, IFN-alpha seems to be the only etiological agent.

Aged↗
PubMed2000

Granulocyte colony-stimulating factor after intensive consolidation chemotherapy in acute myeloid leukemia: results of a randomized trial of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques.

PURPOSE: Ten years after the first clinical studies, the clinical impact of myeloid growth factors in acute myeloid leukemia is still unclear. One of the objectives of the Groupe Ouest-Est Leucémies Aigues Myeloblastiques (GOELAM) 2 trial was to evaluate the benefit of granulocyte colony-stimulating factor (GCSF) given only after the two courses of intensive consolidation chemotherapy (ICC) used to maintain complete remission (CR). PATIENTS AND METHODS: One hundred ninety-four patients who were in CR after induction treatment were randomly assigned to receive G-CSF (100 patients) or no G-CSF (94 patients) after two courses of ICC (ICC 1, high-dose cytarabine plus mitoxantrone; ICC 2, amsacrine plus etoposide). G-CSF (filgrastim) was administered from the day after chemotherapy until granulocyte recovery at a daily dose of 5 microg/kg. RESULTS: In the G-CSF group, the median duration of neutropenia (< 0.5 x 10(9)/L) was dramatically reduced, both after ICC 1 (12 v 19 days, P <.001) and after ICC 2 (20 v 28 days, P <.001). The median duration of hospitalization was also significantly shorter in the G-CSF group (24 v 27 days after ICC 1, P <.001; 29 v 34 days after ICC 2, P <. 001). The median duration of intravenous antibiotics was significantly reduced after ICC 1 and ICC 2, and the median duration of antifungal therapy was significantly reduced after ICC 1. However, the incidence of microbiologically documented infections, the toxic death rate, the 2-year disease-free survival, and the 2-year overall survival were not affected by G-CSF administration. Moreover, the median interval between ICC1 and ICC2 was reduced by only 2 days, and the number of patients undergoing ICC2 was not increased in the G-CSF arm. CONCLUSION: G-CSF should be administered routinely after ICC to reduce the duration of neutropenia and hospitalization. However, G-CSF did not seem to significantly increase the feasibility of this two-course program or modify overall outcome.

Acute Disease↗
PubMed1999

An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: developed for the American Society of Hematology.

Because there are differing opinions regarding treatment of patients in the chronic phase of chronic myeloid leukemia (CML), the American Society of Hematology convened an expert panel to review and document evidence-based benefits and harms of treatment of CML with busulfan (BUS), hydroxyurea (HU), recombinant interferon-alpha (rIFN-alpha), and bone marrow transplantation (BMT). The primary measure for defining efficacy was survival. Analysis indicated a survival advantage for HU over BUS. Observational studies of rIFN-alpha suffer from numerous biases including sample size, variations in study populations, definitions of hematologic and cytogenetic remissions, and dose. That rIFN-alpha is more efficacious than chemotherapy is demonstrated by 6 prospective randomized trials. For patients with favorable clinical features in chronic phase, compared to HU and BUS, rIFN-alpha improves survival by a median of about 20 months. Most evidence suggests that rIFN-alpha is most effective when combined with other drugs and when given during the earliest stage of the chronic phase. Adding cytarabine to rIFN-alpha adds further survival benefit but increases toxicity. Limitations for evaluating the long-term benefits of allogeneic BMT include the retrospective nature of most studies, incomplete documentation of the clinical characteristics of the patients, paucity of the details on patient selection, lack of control groups, and limitations of survival calculations. Survival curves for BMT show that at least half of the patients transplanted remain alive 5 to 10 years after treatment, whereas similar curves for rIFN-alpha show a continuous relapse rate over time with the curves crossing at about 7 to 8 years. Estimates of long-term survival may be confounded by the selection biases mentioned and the analytic methods used. The magnitude of the incremental increase in benefit with BMT must be weighed against the potential serious harm and death that may accompany the procedure in the short term. The best results with BMT have been obtained when it is performed within 1 to 2 years from diagnosis. Since each treatment option involves tradeoffs between benefit and harm, patient choice must be based on the examination of facts presented in an unbiased fashion. Newly diagnosed younger patients and older patients who are candidates for BMT should also be offered information about IFN-based regimens, the tradeoffs involved, and, if possible, share in the treatment decision. Hopefully this analysis will provide the stimulus for evaluation of other important aspects of CML.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial.

Stem cell factor (SCF) has been shown to synergize with filgrastim to mobilize CD34(+) cells into the peripheral blood. To determine if addition of SCF to chemotherapy and filgrastim reduces the number of leukaphereses required to achieve a target yield of 5 x 10(6) CD34(+) cells/kg, 102 patients with multiple myeloma were randomized to receive mobilization chemotherapy with cyclophosphamide (4 g/m(2)) and either SCF (20 micrograms/kg/d) combined with filgrastim (5 micrograms/kg/d) or filgrastim alone (5 micrograms/kg/d), administered daily until leukaphereses were completed. After collection, patients were treated with myeloablative therapy supported by autologous peripheral blood progenitor cell (PBPC) infusion and filgrastim (5 micrograms/kg/d). There was a significant difference between the treatment groups in the number of leukaphereses required to collect 5 x 10(6) CD34(+) cells/kg (median of 1 v 2 for SCF + filgrastim and filgrastim alone, respectively, P =.008). Patients receiving the combination of SCF plus filgrastim had a 3-fold greater chance of reaching 5 x 10(6) CD34(+) cells/kg in a single leukapheresis compared with patients mobilized with filgrastim alone. The median CD34(+) cell yield was significantly increased for the SCF group in the first leukapheresis (11.3 v 4.0 x 10(6)/kg, P =.003) and all leukaphereses (12.4 v 8.2 x 10(6)/kg, P =.007). Total colony-forming unit-granulocyte-macrophage (CFU-GM) and mononuclear cell counts were also significantly higher in the SCF group in the first leukapheresis and in all leukaphereses. As expected for patients mobilized to an optimal CD34(+) cell yield, the time to engraftment was similar between the 2 treatment groups. Cells mobilized with the combination of SCF plus filgrastim were thus considered effective and safe for achieving rapid engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate injection site reactions being the most frequently reported adverse events. There were no serious allergic-like reactions to SCF. The addition of SCF to filgrastim after cyclophosphamide for PBPC mobilization resulted in a significant increase in CD34(+) cell yield and a concomitant reduction in the number of leukaphereses required to collect an optimal harvest of 5 x 10(6) CD34(+) cells/kg.

Adult↗
PubMed1999

Cat-scratch disease simulating a malignant process of the chest wall.

UNLABELLED: Cat-scratch disease is a well-known cause of regional adenopathy in immunocompetent children. Rarely, patients may present with symptoms simulating a neoplastic disease. The case of a 12-year-old boy with fever, swelling of the chest wall and hepatosplenic nodules is reported. Histological analysis of biopsy specimen obtained from the chest wall lesion and the liver revealed granulomatous reaction without malignant cells. Serological investigations were positive for Bartonella species. The symptoms and the lesions disappeared after oral antibiotic therapy (ciprofloxacin) was started. The patient remained symptom-free 12 months later. CONCLUSION: The present case emphasizes the wide spectrum of clinical manifestations associated with cat-scratch disease which should be investigated as differential diagnosis of manifestations suggesting a neoplastic disease in children.

Bartonella↗
PubMed1999

Syngeneic transplantation in multiple myeloma - a case-matched comparison with autologous and allogeneic transplantation. European Group for Blood and Marrow Transplantation.

Twenty-five patients with multiple myeloma received bone marrow grafts (n = 24) or peripheral blood stem cells (n = 1) from twin donors. The outcome was compared in a case-matched analysis to 125 patients who underwent autologous transplantation, and 125 who underwent allogeneic transplantation. Seventeen patients (68%) receiving twin transplants entered complete remission, which was not significantly different from that of autologous (48%) or allogeneic (58%) transplants. The median overall and progression-free survival for the twins was 73 and 72 months, respectively. The overall survival tended to be better (73 vs 44 months) and the progression-free survival was significantly better (72 vs 25 months) than with autologous transplantation and both were significantly better than with allogeneic transplantation. Three of 17 patients who entered complete remission following transplantation had relapsed at follow-up. This relapse rate was significantly lower than following autologous transplantation and similar to the relapse rate with allogeneic transplantation. Only two twins died of transplant-related toxicity. Six further patients died of progressive or relapsing disease. Syngeneic transplantation in multiple myeloma appears to be the treatment of choice if a twin donor is available. A lower relapse risk than in autotransplantation may be due to reinfusion of malignant cells in some patients treated with this modality or to the presence of a graft-versus-myeloma effect in some syngeneic transplants.

Adult↗
PubMed1999

High-dose chemotherapy with hematopoietic stem cell transplantation in adults with bone marrow relapse of medulloblastoma: report of two cases.

Extraneural relapses of medulloblastoma are associated with a very poor outcome. We present two cases of young adults who developed bone marrow metastases after treatment of medulloblastoma. A very good response to a sequentially scheduled combination of carboplatin and etoposide was observed. Then, high-dose chemotherapy was delivered consisting of busulfan and thiotepa followed by infusion of autologous hematopoietic stem cells. Toxicity of the conditioning regimen was acceptable. The patients remained free of disease 20 and 27 months from the time of relapse, respectively. Further studies are needed to evaluate the impact of high-dose chemotherapy in terms of survival of such patients.

Adult↗
PubMed1999

Allogeneic bone marrow transplantation in aggressive non-Hodgkin's lymphoma (excluding Burkitt and lymphoblastic lymphoma): a series of 73 patients from the SFGM database. Sociét Française de Greffe de Moelle.

The place of allogeneic bone marrow transplantation (BMT) in the treatment of aggressive non-Hodgkin's lymphoma (NHL) remains controversial. We conducted a retrospective study of French experience in allografting NHL between 1984 and 1994. To improve the homogeneity of the study population, cases of low-grade, Burkitt and lymphoblastic NHL were excluded. 73 patients were included in the analysis. Median age at transplantation was 35 years (range 9-61 years); 64 patients were in stage IV and 45 had bone marrow involvement at diagnosis. At the time of transplantation, 46 patients had sensitive disease (25 in complete remission; CR). The overall survival (OS) and progression-free survival (PFS) rates were 41% and 40% respectively at 5 years (median follow-up of survivors 90 months). The probability of disease progression was 30% at 5 years, and only one relapse occurred after 15 months. 32 patients died of transplantation-related complications. In multivariate analysis, pretransplant complete remission was the main factor associated with longer survival (OS at 60 months of 76% among the 25 patients in CR at transplant and of 23% among the 48 patients not in CR at transplant). Neither acute nor chronic graft-versus-host disease (GvHD) influenced the relapse rate. In conclusion, in this high-risk population the overall results of allogeneic BMT were encouraging, despite a high transplant-related mortality rate. We believe this procedure should be studied further in prospective controlled trials.

Adolescent↗
PubMed1998

[Down the claws!].

Explore the source record for details and available documents.

Bartonella henselae↗
PubMed1998

Ten-year results of a strategy combining three cycles of ABVD and high-dose extended irradiation for treating Hodgkin's disease at advanced stages.

BACKGROUND: The treatment of Hodgkin's disease (HD) at advanced stages relies mainly upon multi-agent chemotherapies (CT), while the role of radiation therapy has not been definitely identified. The aim of this report is to analyze the 10-year results of a prospective study including 133 patients with HD clinical stages (CS) IIIA to IVB treated by three monthly courses of ABVD (adriamycin, bleomycin, vinblastin, and dacarbazine) followed by high-dose subtotal or total lymphoid irradiation [(S)TLI]. PATIENTS AND METHODS: From 1 October 1981 to 30 September 1988, 133 adult patients with HD CS IIIA (45), IIIB (33), IVA (seven) and IVB (48) were entered in the non-randomized multicentric prospective trial POF81/34. The number of involved nodal areas (NINA), and the number of visceral sites (NVIS) involved were registered in all patients; patients with bulky mediastinal tumor (BuMT) (mediastinal mass ratio > or = 0.45) were also identified. All patients received three monthly cycles of ABVD. Patients in complete remission (CR) or partial remission (PR) after completion of CT received a (S)TLI including the spleen (involved sites 40 Gy, non-involved 30 Gy); initially involved lung(s) and liver received 18 and 20 Gy, respectively; and patients not in CR or PR after CT or RT received salvage treatments. Univariate and multivariate analyses were performed to identify the factors contributing significantly to the prognosis; initial characteristics, as well as status after the three cycles of CT, were entered in the model. RESULTS: Of the 133 patients, 74 (55.6%) entered in CR after CT and 116 (87.2%) after completion of radiation therapy. Ten-year freedom from progression (FFP), freedom from tumor mortality (FFTM) and survival rates were 70.4%, 78.9% and 70.6%, respectively. According to univariate analysis the NVIS (< or = one vs. > or = two) was the only initial factor simultaneously influencing 10-year FFP (73.9% vs. 38.2%) FFTM (82.5 vs. 34.1%) and survival (73.5% vs. 17.3%) rates; on the other hand, the NINA (< or = four vs. > or = five) influenced FFP (81.4% vs. 60.7%) and FFTM rates (87.3% vs. 71.4%) while symptoms (A vs. B) influenced FFP (80.7% vs. 63.3%) and survival (82.8% vs, 61.2%) rates. Finally, age (< 40 vs. > or = 40) influenced survival rate only (79.2% vs. 50%). According to multivariate analysis, NVIS and NINA had an independent impact on FFP and FFTM, while survival was modified by the NVIS and age. The post-CT status (CR vs. no CR) had a major impact on FFP (85.3% vs. 64.9%) FFTM (92.1% vs. 63.3%) as well as on survival (78.6% vs. 54.7%) rates in both univariate and multivariate analyses. Complications of therapy were mainly due to RT: 11 patients acquired second malignancies, six developed lung fibrosis or severe pulmonary infections, three developed intestinal obstructions and six developed angina pectoris or carotid stenosis. CONCLUSIONS: Tumor burden (identified by the number of involved nodal areas and the number of visceral sites) and the response to initial CT were the two independent factors influencing the outcome of this group of 133 patients with HD, CSIII and IV treated by three cycles of ABVD followed by high-dose [(S)TLI].

Adult↗
PubMed1998

Identification of several genes differentially expressed during progression of chronic myelogenous leukemia.

The Bcr-Abl fusion protein plays a crucial role in the initiation and maintenance of chronic myelogenous leukemia (CML). However, additional events are necessary for the transition from the chronic phase to the terminal phase of the disease. To identify genes involved in the disease progression, we constructed a subtractive library from enriched K562 cell mRNA. We obtained 1084 cDNA clones. After a specific hybridization of these clones with a cDNA probe from either chronic phase or K562 cells, 43 clones which present a differential hybridization level have been selected. Among them, several clones corresponded to ribosomal protein genes showing an increased transcription level during the blast crisis. We observed variations in the expression of a cellular adhesion molecule, a laminin-binding protein. An increased transcription level of the MAZ gene has been shown in the terminal phase of the disease. This gene encodes a protein that regulates the transcription of myc.

Blast Crisis↗
PubMed1998

Does BCR-ABL genomic rearrangement persist in CML patients in complete remission after interferon alpha therapy?

Cytogenetic, interphase fluorescent in situ hybridization (FISH) and RT-PCR methods were used to study minimal residual disease in peripheral blood stem cells collected for autografting in three chronic myeloid leukemia (CML) patients in sustained complete cytogenetic remission after treatment with interferon alpha (IFNalpha). Karyotypic analysis failed to reveal Ph-positive metaphases. FISH detected 9-16% nuclei with a BCR-ABL fusion gene, contrasting with RT-PCR, performed in two cases, which was negative in one case and weakly positive in the other. RT-PCR was also subsequently weakly positive in the third patient. This discrepancy suggests that the BCR-ABL genomic rearrangement persists unexpressed in quiescent cells. These preliminary results, which need to be confirmed in larger series, suggest that monitoring residual disease in CML should be performed both at DNA and RNA levels. Moreover, autografting following IFNalpha therapy should be considered with caution because of the persistence of the BCR-ABL genomic rearrangement in a sizeable proportion of the cells.

Adult↗
PubMed1998

t(3;17)(q21;q25) in Epstein-Barr virus associated peripheral T-cell lymphoma: a paediatric case.

We describe an immunocompetent 8-year-old boy with a serological profile indicating chronic infection by Epstein-Barr virus (EBV) who developed subcutaneous and pulmonary lesions related to a peripheral T-cell proliferation. No clonal rearrangement of T-cell receptor or immunoglobulin genes was seen. However, the finding of a t(3;17)(q21;q25) in 44 metaphases from one skin lesion demonstrated a clonal origin. We also showed that the proliferative T cells contained EBV genome leading to the diagnosis of EBV-associated peripheral T-cell lymphoma. Further cytogenetic and molecular studies are needed to identify genes implicated in the pathogenesis of this haematological malignancy.

Child↗
PubMed1998

Interferon-alpha: mechanisms of action in chronic myelogenous leukemia in chronic phase.

Interferon-alpha has been shown to induce complete haematologic responses in chronic myelogenous leukemia patients and also cytogenetic responses. There is a clear correlation between cytogenetic responses and survival improvement. There is not a unique mechanism of action of IFN-alpha. IFN-alpha acts directly against leukemic cells and there are also other mechanisms of action such as immune stimulation, gene regulation and growth factors or interleukin stimulation.

Antineoplastic Agents↗
PubMed1997

Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).

Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.

Acute Disease↗