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P Rousselot

Publications and source records attributed to P Rousselot.

At least 19 recordsLinked to original sources
PubMed2002

Results of a phase II trial of a combination of oral cytarabine ocfosfate (YNK01) and interferon alpha-2b for the treatment of chronic myelogenous leukemia patients in chronic phase.

Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials.

Administration, Oral↗
PubMed2002

Prognostic significance of FLT3 internal tandem repeat in patients with de novo acute myeloid leukemia treated with reinforced courses of chemotherapy.

FLT3 internal tandem duplications (FLT3-ITDs) are present in nearly 25% of patients with AML and have been associated with poor response to conventional therapy and poor outcome. We retrospectively evaluated the effect of reinforced courses of chemotherapy on the prognostic value of FLT3-ITDs in 159 AML patients prospectively enrolled in the ALFA-9000 trial, which randomly compared three reinforced induction regimens (standard 3+7 including high-dose daunorubicin, double induction, and timed-sequential therapy). FLT3-ITD was present in 40/159 (25%) blast samples and associated with high WBC (P = 0.002) and cytogenetics (P < 0.001) with a higher incidence (35%) in patients with a normal karyotype. There was no difference in CR rate between FLT3-wt and FLT3-ITD patients (80% vs 78%). Relapse-free survival (RFS) was similar in both groups (5-year RFS, 33% vs 32%; P = 0.41), even after adjustment for age, sex, WBC, cytogenetics, and treatment arm. A trend to a worse survival was observed in the FLT3-ITD group (estimated 5-year OS, 23% vs 37%; P = 0.09), mainly in patients with a normal karyotype. This was associated with a dramatic outcome in relapsing FLT3-ITD patients (estimated 3-year post-relapse survival, 0% vs 27%; P = 0.04). These results suggest that the bad prognosis associated with FLT3-ITDs in AML might be partly overcome using reinforced chemotherapy. Early detection of FLT3 mutations might thus be useful to intensify induction as well as post-remission therapy in FLT3-ITD patients.

Acute Disease↗
PubMed2001

Expression of high Km 5'-nucleotidase in leukemic blasts is an independent prognostic factor in adults with acute myeloid leukemia.

Cytarabine (ara-C) requires activation into its triphosphorylated form, ara-CTP, to exert cytotoxic activity. Cytoplasmic 5'-nucleotidase (5NT) dephosphorylates ara-CMP, a key intermediate, preventing accumulation of ara-CTP and may reduce cellular sensitivity to the cytotoxic activity of ara-C. To determine whether the level of expression of 5NT is correlated with clinical outcome in patients with acute myeloid leukemia (AML) treated with ara-C, this study analyzed the levels of messenger RNA expression of high Km 5NT by real-time polymerase chain reaction at diagnosis in blast cells of 108 patients with AML. High Km 5NT was expressed at diagnosis in the blast cells of 54% of patients. In univariate analysis, (1) patients whose blast cells contained high levels (values greater than the median value for total population) of high Km 5NT at diagnosis had significantly shorter disease-free survival (DFS) than patients with low levels of high Km 5NT (11 months versus 17.5 months, P =.02) and (2) high levels of high Km 5NT also predicted significantly shorter overall survival (15.7 months versus 39 months, P = .01) in young patients (< or = 57 years; median value for the entire population). In a multivariate analysis taking into account age, karyotype risk, and other factors found to have prognostic significance in univariate analysis, (1) high Km 5NT expression was an independent prognostic factor for DFS and (2) high levels of high Km 5NT also predicted significantly shorter overall survival in young patients. These results demonstrate that the expression of high levels of high Km 5NT in blast cells is correlated with outcome in patients with AML.

5'-Nucleotidase↗
PubMed2001

Primary plasma cell leukaemia: a report of 18 cases.

Primary plasma cell leukaemia (P-PCL) is a variant of multiple myeloma (MM) first diagnosed in the leukemic phase, with >2000/mm(3) circulating plasma cells (PCs) and plasmacytosis >20% of the white cell count. We investigated the clinical characteristics, therapy, immunophenotype and prognosis factors of 18 patients. Common features at diagnosis were asthenia (seven patients), renal insufficiency (ten patients), bone pain (seven patients), splenomegaly or hepatomegaly (five patients). Hypercalcemia was present at diagnosis in seven patients and was the most potent poor prognosis factor (P<0.05). Most patients (16 out of 18) were treated with an anthracyclin containing regiment; complete remission was attained in one patient and partial remission in 11 patients while six patients had no response. The median survival time from diagnosis was 7 months (2--12, 95% confidence interval), but response to treatment had favorable predictive value (P<0.05). The PCs were usually positive for mature B-cell markers (PCA-1, CD38). They expressed integrins which may increase their binding to endothelial cells and thus participate in PCL physiopathology by favoring plasmocyte extramedullary spread.

Adult↗
PubMed2001

[Pseudotumoral presentation of cat scratch disease].

BACKGROUND: A frequent cause of chronic benign lymphadenopathy, cat-scratch disease (CSD) occurs mainly in children and young adults. Bartonella henselae is the agent responsible for CSD. The most common symptoms of the disease are regional lymphadenopathy and fever. Atypical forms occur in about 10% of patients; among them, CSD may initially present as a tumor. CASE REPORT: A 4-year-old child developed a 'tumor' of the arm with fever. The values of white blood cell count and CRP were normal. Ultrasonography, MRI and arteriography did not contribute to the diagnosis, which was established on histologic examination and serologic test for infection with B. henselae. The outcome was favorable with antibiotic treatment. CONCLUSION: In case of tumor of the limbs, cat-scratch disease should be searched for.

Anti-Bacterial Agents↗
PubMed2001

Relationship between environmental fungal contamination and the incidence of invasive aspergillosis in haematology patients.

Invasive aspergillosis (IA) is a major opportunistic infection in haematology patients. Spore inhalation is the usual route of Aspergillus infection, suggesting a determining role of environmental contamination by spores in the epidemiology of IA. We prospectively examined the relationship between environmental contamination by Aspergillus and other fungal species and the incidence of invasive nosocomial aspergillosis (INA) in a bone marrow transplantation unit and two haematology wards. During a four-year period, levels of air and surface fungal contamination were determined bi-monthly in patients' rooms (some equipped with HEPA filters and LAF systems), and various common sites in each ward (corridors, nursing stations, etc.). Results were compared to the incidence of INA. A total of 3100 air and 9800 surface samples were collected, and 79 cases of IA were diagnosed, of which 64 were probably or possibly INA. Patterns of fungal contamination were comparable in the three wards, with a gradient ranging from high levels in common sites to a virtual absence in rooms equipped with HEPA filters and LAF systems. Using a regression model, a significant relationship was found between the incidence of INA and the degree of fungal contamination of air and surfaces in conventional patient rooms (not equipped with HEPA) and common sites. This study shows that in a non-epidemic setting, there is a significant relationship between environmental fungal contamination in haematology wards and the incidence of INA. Our findings underline the importance of environmental surveillance and strict application of preventive measures.

Aspergillosis↗
PubMed2001

[HBME-1 immunostaining in thyroid pathology].

The aim of this study was to evaluate wether HBME-1 immunohistochemical analysis can reliably differentiate benign thyroid lesions from thyroid carcinomas. Fifty benign and 87 malignant lesions were analyzed. All papillary carcinomas (67/67) were HBME-1 positive, as well as 14 of 20 follicular well-differentiated carcinomas and 13 of 29 atypical follicular adenomas and 4 out of 21 goiters were weakly and focally positive. HBME-1 highlighted micronests of papillary carcinomas. The reactivity of HBME-1 in the tall-cell variant of papillary carcinomas was apical and stronger than in classical papillary carcinomas. Positive HBME-1 immunostaining is in support of the diagnosis of the follicular variant of papillary carcinoma and highlights micropapillary carcinomas. HBME-1 may be of additional value in the diagnosis of thyroid malignancy.

Adenocarcinoma, Follicular↗
PubMed2001

[Angiomatoid fibrous histiocytoma: a rare pathologic entity].

Angiomatoid fibrous histiocytoma is an unusual tumor, affecting primarily young adults who develop local disease with favorable prognosis. This contrasts with the aggressive natural history of malignant fibrohistiocytoma. We report case of a 9-year-old girl who presented with a tumor mass of soft tissues with an unusual deep location, thereby with non distinctive clinical features. Surgical treatment was performed.

Bone and Bones↗
PubMed2000

Restaging with gallium scan identifies chemosensitive patients and predicts survival of poor-prognosis mediastinal Hodgkin's disease patients.

UNLABELLED: Following treatment of mediastinal Hodgkin's disease (HD), residual masses are frequent and gallium scanning has proven to be of value in the evaluation of their specificity (fibrosis or active disease). This study assessed, for relapse and survival, the predictive value of restaging gallium scan of patients with a residual mass on computed tomography scan after induction chemotherapy. Between 1/89 and 12/97, in 53 newly diagnosed HD patients with a residual mediastinal mass, a gallium scan was performed after chemotherapy (3 or 4 courses) and always before consolidative radiotherapy. Characteristics at diagnosis were: nodular sclerosis histology, 89%; bulky mediastinal disease, 79%; B-symptoms, 51%. RESULTS: gallium scan was positive in 16 patients (30%) and negative in 37 (70%). At median follow-up period of 36 months, freedom-from-progression rate was 86% versus 19% (P<0.0001) for patients with negative vs positive gallium scans, respectively. The 5-year overall survival (OS) rate was 68% and differed significantly (P<0.0001) between negative (91%) and positive (25%) gallium scanning groups. The specificity of gallium scanning was 91% and the sensitivity 72% with a positive predictive value of 81% and a negative predictive value of 86%. Evaluation with gallium scan after induction chemotherapy identifies chemosensitive patients among those with poor-prognosis mediastinal HD. Although relapse may occur in patients with negative gallium scan, a postive gallium scan is highly predictive of failure and poor outcome, and treatment should thus be modified.

Adult↗
PubMed2000

Myelodysplasias and leukemias after autologous stem cell transplantation for lymphoid malignancies.

The incidence of secondary myelodysplastic syndromes and acute leukemia (MDS/AL) was reported for 395 patients autografted for Hodgkin's disease (HD) (n = 96) and non-Hodgkin's lymphoma (NHL) (n = 299) between 1987 and 1998. Eleven patients developed secondary MDS/AL (crude rate at 2.8%) including two lymphoblastic AL cases. The mean time of occurrence was at 32 months after autologous stem cell transplantation (ASCT) and 71 months after diagnosis. The estimated actuarial incidence at 10 years was at 6.3% (+/-4%). Karyotyping revealed complex chromosomal aberrations in only one patient, and two translocations [t(8;21) and t(8;16)]. No features of topoisomerase II inhibitor-related leukemia were found. Only one patient had received ASCT in first remission. The remaining 10 patients had received multiple courses of chemotherapy before stem cell collection and four had relapsed after ASCT and before the occurrence of secondary MDS/AL. Five of 11 patients had received localized radiotherapy and five others received TBI in their conditioning regimen. Ten patients died despite chemotherapy and/or supportive care and only one patient is alive and well after genoidentical allogeneic transplantation. We suggest a cumulative leukemogenic role of pre-ASCT radiation and chemotherapy in the occurrence of these secondary MDS/AL more than the high-dose therapy itself.

Acute Disease↗
PubMed2000

Functional G-CSF pathways in t(8;21) leukemic cells allow for differentiation induction and degradation of AML1-ETO.

INTRODUCTION: Efficacy of differentiating agents requires that their specific cellular targets are still expressed and functional in the leukemic cells. One hypothesis to target sensitive cells is to select leukemic clones which harbor disrupted transcription factors. CBFalpha and CBFbeta are core-binding proteins which have been identified as transcription regulators of hematopoietic genes and shown to be altered in numerous leukemias. In M2 AML, the t(8;21) translocation, CBFalpha (AML1) is altered and produced as the AML1-ETO fusion protein. The fusion protein blocks transcription and differentiation mediated by G-CSF. Interestingly, AML1-ETO leukemic cell lines are sensitive to numerous cytokines in vitro and can be induced to differentiate in the presence of G-CSF and PMA. MATERIALS AND METHODS: As in the APL differentiation model, primary culture provides a useful tool for therapeutic screening of differentiation inducers, we analysed the in vitro sensitivity of 10 fresh M2 AML t(8;21) leukemic samples to G-CSF and the functionality of G-CSF intracellular pathways. In vitro data were compared with in vivo data from four patients treated with rhG-CSF at the dosage of 5 microg/kg/day i.v. for two to three weeks before the initiation of AML induction chemotherapy and immunophenotypic analysis performed weekly to monitor in vivo differentiation. RESULTS: In vitro, an increase in CD34+ cells expressing differentiation antigens (CD11b, CD13 or CD15) was noted along with a decrease of immature CD34+/differentiation antigen negative cells. After two weeks of a daily rhG-CSF administration in vivo, a significant, albeit transient, decrease of blast count was achieved, concomitant with an increase in differentiated leukemic cells suggesting that in vivo differentiation occurs. Fresh t(8;21) leukemic cells possess functional G-CSF signaling pathways as normal activity and kinetics of STAT1 and STAT3 binding was observed. Furthermore, differentiation induction leads to a subsequent degradation of the AML1-ETO oncoprotein. CONCLUSION: The data presented here supports the claim that G-CSF can induce in vitro and in vivo differentiation of M2 AML t(8;21) cells.

Antigens, CD↗
PubMed2000

Expression and prognostic significance of survivin in de novo acute myeloid leukaemia.

Survivin is an inhibitor of apoptosis (programmed cell death) overexpressed in various human cancers, but undetectable in normal differentiated tissues. A potential distribution and prognostic significance of survivin in patients with de novo acute myeloid leukaemia (AML) was investigated. By immunofluorescence of bone marrow specimens and peripheral blood mononuclear cells, survivin was detected in 75 out of 125 interpretable AML cases (60%), with reactivity in 50-90% of AML cells. Survivin expression correlated with a lower white blood cell count (WBC) (P = 0.008 by the Mann-Whitney test) and was associated, in the 55 cases of FAB M0/M1/M2, with leukaemic granulocytic maturation (one out of five M/L0, 11 out of 22 M/L1 and 23 out of 28M/L2; P = 0.007 by the Fisher test). In 69 patients treated with the Acute Leukaemia French Association (ALFA) 9000 protocol, survivin expression was significantly associated with a lower WBC (P = 0.03 by the Mann-Whitney test) and favourable/intermediate cytogenetics (P= 0.03 by the Fisher test). There was no significant difference in complete remission rate or overall survival between survivin-positive and survivin-negative AML patients (P = 0.15 by the log-rank test). However, survivin expression became an independent negative prognostic factor for survival when adjusted with the Cox model for established prognostic factors in AML (cytogenetics, age and WBC) or for the ALFA 9000 treatment arm (RR = 2.8 and P = 0.026, by the likelihood-ratio test). These data suggest that survivin expression may be considered as a new unfavourable prognostic factor of de novo AML and suggest a role for apoptosis inhibition in influencing disease outcome.

Acute Disease↗
PubMed2000

Liver adenomatosis: reappraisal, diagnosis, and surgical management: eight new cases and review of the literature.

OBJECTIVE: Liver adenomatosis (LA) is a rare disease originally defined by Flejou et al in 1985 from a series of 13 cases. In 1998, 38 cases were available for analysis, including eight personal cases. The aim of this study was to review and reappraise the characteristics of this rare liver disease and to discuss diagnosis and therapeutic options. BACKGROUND: LA was defined as the presence of >10 adenomas in an otherwise normal parenchyma. Neither female predominance nor a relation with estrogen/progesterone intake has been noted. Natural progression is poorly known. METHODS: The clinical presentation, evolution, histologic characteristics, and therapeutic options and results were analyzed based on a personal series of eight new cases and an updated review of the literature. RESULTS: From a diagnostic standpoint, two forms of liver adenomatosis with different presentations and evolution can be defined: a massive form and a multifocal form. The role of estrogen and progesterone is reevaluated. The risks of hemorrhage and malignant transformation are of major concern. In the authors' series, liver transplantation was indicated in two young women with the massive, aggressive form, and good results were obtained. CONCLUSION: Liver adenomatosis is a rare disease, more common in women, where outcome and evolution vary and are exacerbated by estrogen intake. Most often, conservative surgery is indicated. Liver transplantation is indicated only in highly symptomatic and aggressive forms of the disease.

Adenoma, Liver Cell↗
PubMed2000

Evaluation of minimal residual disease using reverse-transcription polymerase chain reaction in t(8;21) acute myeloid leukemia: a multicenter study of 51 patients.

PURPOSE: Most studies using various reverse-transcription polymerase chain reaction (RT-PCR) techniques reported that the detection of the AML1-ETO fusion transcript was a common finding in long-term complete remission (CR) in acute myeloid leukemia (AML) with t(8;21) translocation. However, larger prospective studies with interlaboratory quality control may be important to investigate more precisely the clinical usefulness of studying minimal residual disease with RT-PCR in t(8;21) AML. PATIENTS AND METHODS: We collected 223 marrow samples from 51 patients with t(8;21) AML diagnosed in five centers and tested all samples by two different RT-PCR techniques (a nested technique and a one-step technique, with a sensitivity of 10(-6) and 10(-5), respectively) in two different laboratories. RESULTS: Samples from 14 patients in long persistent CR (median follow-up duration, 112 months) were taken at least twice, and all were PCR-negative by both techniques. Samples were prospectively taken from 37 patients after achievement of first CR and/or second CR, before intensive consolidation treatment, and every 3 to 6 months after completion of therapy. Patients who converted to PCR negativity with the one-step technique (60%) or both techniques (48%) after CR achievement had a longer CR duration than those with persistently positive PCR results (two-sided log-rank test, P =.0001). Patients who became PCR-negative with the one-step technique before intensive consolidation (23%) had a lower relapse rate (11% v 72%) and a longer CR duration than those who remained persistently PCR-positive at that point (two-sided log-rank test, P =.0015). CONCLUSION: Patients with AML with t(8;21) in long-term remission were all PCR-negative. In prospectively studied patients, a good correlation was found between negative PCR results and absence of relapse. Early negative results with the one-step RT-PCR technique, before consolidation treatment, seemed to carry an especially good prognosis, suggesting that RT-PCR analysis could help in choosing the type of consolidation therapy in patients with t(8;21) AML.

Acute Disease↗