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J A Gastaut

Publications and source records attributed to J A Gastaut.

At least 19 recordsLinked to original sources
PubMed2006

A phase II trial of rituximab as adjuvant to intensive sequential chemotherapy in patients under 60 years with untreated poor-prognosis diffuse large B-cell lymphoma.

The potential benefit of rituximab as adjuvant to high-dose therapy (HDT) has been investigated in patients under 60 years with poor-risk (age-adjusted international prognostic index at 2-3) CD20+ diffuse large B-cell lymphoma (DLBCL). The treatment consisted of four cycles of high-dose CEOP (cyclophosphamide, epirubicin, vincristine, prednisone), plus etoposide and cisplatin during the two last cycles. Peripheral blood stem cells were collected after cycle 1, and reinfused after cycles 3 and 4. Four weekly rituximab infusions were subsequently delivered. Among the 36 patients included, 30 could complete chemotherapy schedule, and 24/36 received rituximab. A complete response occured in 26/36 patients (72%). With a median follow-up of 30 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- s.d.) were 65 +/- 16 and 63 +/- 15%, respectively. For the 24 patients who received both chemotherapy and rituximab, the estimated 5-year OS and EFS rates were 86 +/- 14 and 82 +/- 15%. These data suggest that rituximab after HDT is feasible. Both complete remission rate and survival curves compare favorably with the poor outcome usually observed in high-risk DLBCL patients managed with HDT without rituximab.

Adult↗
PubMed2005

Nelfinavir in HIV-HCV coinfected patients: a 24-month follow-up in a cohort of 82 patients.

This retrospective and longitudinal study evaluated the long-term hepatic tolerance of a nelfinavir (NFV)-antiretroviral combined regimen in 82 patients of the HCV-HIV Cohort of CISIH-Sud of Marseilles. Follow-up data (liver enzyme levels, CD4 cell count, HIV viral load, and metabolic parameters) of patients treated with NFV on inclusion or during the follow-up of the cohort were analyzed under treatment over 24 months. Comparisons were performed with X2 or Kruskal-Wallis tests. At baseline (n = 82), the median exposure to NFV was 4.1 months; 58 patients received NFV combined with NRTI and 24 with NNRTI. The median CD4 cell count was 337/mm3 [interquartile range (IR): 216-480) and 39.7% had an undetectable HIV RNA level. Qualitative HCV PCR was positive in 91% of the patients and 19/51 patients with liver biopsy were F3-F4. Median alanine and aspartate aminotransferase (ALAT, ASAT), gamma-glutamyltransferase (GT), and alkaline phosphatase (ALP) were 46 UI/liter (IR: 36-76), 55 UI/liter (IR: 32-97), 97 UI/liter (IR: 50-194), and 88 UI/liter (IR: 72-104), respectively, with 76% of the patients with ALAT/ASAT grade <2. Median follow-up was 23 months (IR: 13.8-37). No significant difference was observed in the distribution of ALAT, ASAT, GT, and ALP as well as of ALAT/ASAT grades over the 24-month study period. Patients treated with NFV + NNRTI had significantly higher GT and ALP levels at baseline with no significant increase during follow-up. Cholesterol, triglyceride, and glycemia distributions remained stable over time. In conclusion, this study showed a good hepatic and metabolic tolerance of a long-term NFV-combined regimen in HIV-HCV coinfected patients.

Adult↗
PubMed2005

Single-agent thalidomide induces response in T-cell lymphoma.

T-cell lymphoma is an aggressive lymphoma that cannot be cured despite aggressive therapy, including autologous stem cell transplantation. Thalidomide is an immunomodulatory drug with numerous properties that has proven effective in relapsed multiple myeloma and, to a lesser extent, in other hematologic diseases. We report three cases of relapsed refractory T-cell lymphoma treated with thalidomide with a good tumor response.

Aged↗
PubMed2004

Cytomegalovirus-specific immune recovery following allogeneic HLA-identical sibling transplantation with reduced-intensity preparative regimen.

Cytomegalovirus (CMV) represents a major cause of morbidity after allogeneic stem cell transplantation (allo-SCT). Using interferon-gamma-enzyme-linked immunospot (ELISPOT) assay and HLA-peptide tetramers, we analysed 54 patients who received a reduced-intensity conditioning regimen, including fludarabine, busulphan and antithymocyte globulin (ATG), with the aim of defining essential elements of protective immunity to CMV. The cumulative incidence of CMV positive antigenaemia was 37% occurring at a median of 43 days (range, 7-104) after allo-SCT. In univariate analysis, conditioning regimen (ATG dose) and graft characteristics (graft source and CD3+ T-cell dose) significantly influenced CMV-specific immune recovery. A significant correlation (P=0.000002) was found between CMV-specific T cells detected by IFN-gamma ELISPOT assay and pp65-specific CD8+ T-cell frequency quantified by tetramers. CMV-specific CD8+ T cells presented a phenotype of effector cells (perforin and 2B4 positive). In multivariate analysis, bone marrow (BM) as a graft source was the only variable associated with an increased risk of CMV positive antigenaemia (P=0.0001) in line with the ELISPOT assay showing a higher frequency of functional CMV-specific effectors within peripheral blood stem cell grafts as compared to BM. Thus, early monitoring of CMV-specific immune recovery using sensitive new tools might prove useful for patient management after allo-SCT.

Adult↗
PubMed2004

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation.

In all, 41 multiple myeloma (MM) patients received an antithymocyte globulin (ATG), fludarabine, and busulfan-based reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) from HLA-identical siblings. In total, 29 patients (70%) were in partial remission, one patient in complete remission, and 11 (27%) with progressive disease at the time of allo-SCT. Median time between diagnosis and allo-SCT was 24 months. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 36% (95% CI, 21-51%) and 7% (95% CI, 2-20%), respectively. Overall, 10 patients developed limited chronic GVHD, whereas seven developed an extensive form (cumulative incidence, 41% (95% CI, 26-56%) at 2 years). With a median follow-up of 389 days, the overall cumulative incidence of transplant-related mortality (TRM) was 17% (95% CI, 6-28%). In all, 11 patients (27%) are in continuous complete remission, and the Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) at 2 years were 62% (95% CI, 47-76%) and 41% (95% CI, 23-62%), respectively. PFS and OS were significantly higher in patients with chronic GVHD as compared to patients without chronic GVHD (P=0.006 for PFS and P=0.01 for OS). Collectively, these data demonstrate that RIC allo-SCT can mediate a potentially curative graft-versus-myeloma effect with an acceptable incidence of toxicity and TRM.

Adult↗
PubMed2004

Features of extramedullary and extraosseous multiple myeloma: a report of 19 patients from a single center.

Extramedullary (EM) localizations at diagnosis or during the course of multiple myeloma (MM) are rare. We conducted a large retrospective study to more accurately describe the clinical and laboratory features of this entity, and the outcome of these manifestations. The charts of 19 eligible patients out of 432 patients with MM were retrieved from the hematology department of the Institut Paoli-Calmettes Cancer Center. Median age was 61 (range: 39-79) with a female/male sex ratio of 8/11. Ten patients were found to have EM and extraosseous tumor at the time of MM diagnosis, and nine patients developed EM tumor during the course of the disease. Neither the stage of the disease, the LDH level, or the type of immunoglobulin (Ig) was found to be associated with the development of EM disease. Patients who developed EM tumor during the course of MM had a lower serum Ig and a higher monoclonal Bence-Jones proteinuria at the diagnosis of MM than patients who presented with EM tumor at diagnosis. Multiple sites were usually involved. Resistance to chemotherapy was frequent and response to thalidomide was poor. Eight out of the 19 patients responded to high-dose chemotherapy. The remaining 11 patients progressed while on therapy. With a median follow-up of 13 months (range: 2-65), six patients are alive, four patients are in partial remission and two patients in present progressive disease. In conclusion, EM tumors are a rare manifestation of MM, with a cumulative incidence of 4.6% of MM. Multiple sites are usually involved. The response to chemotherapy is very poor with a very low response rate to thalidomide. The prognosis is very poor, especially when the diagnosis of EM tumor is concurrent with the diagnosis of MM.

Adult↗
PubMed2004

Polymorphism and drug-selected mutations in the protease gene of human immunodeficiency virus type 2 from patients living in Southern France.

The susceptibility of human immunodeficiency virus type 2 (HIV-2) to protease inhibitors (PI) is largely unknown. We studied HIV-2 protease genes from 21 HIV-2-infected patients who were exposed or not exposed to PI. The aim of this study was (i). to characterize the polymorphism of HIV-2 protease in the absence of drug, (ii). to know whether the HIV-2 protease gene naturally harbors HIV-1 drug resistance codons, and (iii). to identify mutations emerging under PI-selective pressure. Sixty-five HIV-2 RNA or proviral DNA samples were directly sequenced from the plasma or peripheral blood mononuclear cells of 8 patients who had received PI and 13 patients who had never received any antiretroviral. In untreated patients, the highest amino acid variability in HIV-2 protease was observed at positions 14, 40, 43, 46, 65 and 70, and seven codons (10V, 32I, 36I, 46I, 47V, 71V, and 73A) associated with drug resistance in HIV-1 were highly prevalent. In addition, at six positions (positions 7, 46, 62, 71, 90, and 99), the amino acid variability or the amino acid frequencies or both differed significantly in PI-treated and untreated patients, suggesting that mutations 7K-->R, 46V-->I, 62V-->A/T, 71V-->I, 90L-->M and 99L-->F were occurring under PI-selective pressure. At these positions, at least one sample simultaneously harbored both wild-type and mutated codons, while substitutions at positions 62, 71, 90, and 99 were confirmed in a longitudinal analysis. Moreover, the presence of codons 46I and 99F in the absence of drug in HIV-2 subtype B proteases may reflect natural resistance to PI. In conclusion, the present study revealed that HIV-2 strains harbor specific patterns of natural polymorphism and resistance.

Adult↗
PubMed2003

Rapid improvement of disseminated aspergillosis with caspofungin/voriconazole combination in an adult leukemic patient.

A 57-year-old man with acute myeloid leukemia (AML) French-American-British (FAB) 4 developed disseminated invasive cerebral and pulmonary aspergillosis during postinduction aplasia. According to international consensus, infection was categorized as probable (two host factors: deep neutropenia for >10 days and refractory fever for >96 h; major clinical criteria of lower respiratory tract and CNS invasive fungal infection; positive results for galactomannan antigen in three blood samples). After the failure of standard amphotericin-based therapy, the spectacular regression of multifocal brain and lung lesions was rapidly achieved under a caspofungin acetate/voriconazole combination. Further permanent caspofungin maintenance with voriconazole added during aplasia periods permitted two consolidation courses and autograft-based intensification without any delay.

Antifungal Agents↗
PubMed2003

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen.

In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined. In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days). The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count. In all, 65% of the bacteremia (95% CI 49-81%) were gram negative. The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days. In multivariate analysis, stem cell source (bone marrow; P=0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (>2 mg/kg) represented the major risk factor for bacteremia (P=0.0001). Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause. Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT.

ABO Blood-Group System↗
PubMed2002

Impact of highly active antiretroviral therapy on the incidence of visceral leishmaniasis in a French cohort of patients infected with human immunodeficiency virus.

The incidence of human immunodeficiency virus (HIV)-Leishmania coinfections in France was estimated on the basis of the French Hospital Database on HIV, and risk factors for the occurrence of visceral leishmaniasis (VL) were analyzed by a multivariate Cox model. VL was diagnosed in 165 of 55,626 HIV-infected patients followed since 1992. The incidence of VL decreased from 11.6+/-1.2 per 10,000 persons-years before 1996 to 6.3+/-0.7 per 10,000 persons-years after 1996, the year when highly active antiretroviral therapy (HAART) was initiated in France. The relative hazard (RH) for development of VL was higher in (1) intravenous drug users versus other transmission groups (RH=1.56; 95% CI, 1.13-2.15), (2) patients living in southern France versus those living in northern France (RH=3.36; 95% CI, 2.44-4.61), and (3) patients who had a CD4 cell count of </=50/mm(3) during their follow-up versus those who did not (RH=6.45; 95% CI, 4.27-9.75) but was lower in (4) patients who received antiretroviral therapy including >/=3 drugs versus those who did not (RH=0.41; 95% CI, 0.26-0.65). We found a significant decrease in the incidence of HIV-Leishmania coinfections after 1996, associated with the introduction of HAART in France.

AIDS-Related Opportunistic Infections↗
PubMed2002

Experience of a combination including indinavir 400 mg plus ritonavir 200 mg twice daily in HIV-infected patients: pharmacokinetic data.

Low doses of ritonavir, a strong inhibitor of cytochrome P450 3A4, enhances the pharmacokinetic profile of indinavir with increased serum levels. We assessed the indinavir-ritonavir 400/200 twice daily combination in 17 HIV-infected patients focusing on the pharmacokinetic data and the tolerance of this regimen. IDV trough and peak concentrations were measured by high-performance liquid chromatography. Median indinavir trough and peak concentrations were 553 ng/ml and 3626 ng/ml, respectively. A good tolerance was observed except for three patients who experienced a major toxicity. Only one dose adjustment was related to indinavir toxicity. Considering the fact that Cmax is mainly responsible of the adverse effects, particularly renal stones, the indinavir-ritonavir 400/200 mg twice daily regimen offers a well-tolerated combination with an increased Cmin but a lower Cmax compared with both the standard tid regimen and higher dose of IDV-RTV regimens.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Features of large granular lymphocytes (LGL) expansion following allogeneic stem cell transplantation: a long-term analysis.

Large granular lymphocyte (LGL) proliferation typically follows a chronic course during which major features are cytopenia and immune abnormalities. Elevated numbers of LGL were reported in a few cases following allogeneic stem cell transplantation (allo-SCT). In this report, we present a retrospective analysis of LGL cases that occurred following allo-SCT in a cohort of 201 consecutive patients transplanted over a period of 7 years. Six cases were identified and LGL expansion occurred more frequently following a reduced fludarabine and anti-T lymphocyte globulin-based preparative regimen (4 cases/49), than after a conventional myeloablative regimen (2 cases/152). Expansion of LGL was seen between 3 and 15 months following allo-SCT. Hematopoiesis, with mild to severe cytopenia, was a favored target for LGL. Autoimmune manifestations including polyarthritis and hypergammaglobulinemia were also observed. LGL proliferation was observed in the context of chronic antigenic stimulation associated with recurrent viral infections especially CMV. Moreover, five out of these six high risk patients achieved a long-term complete remission concomitant or following LGL expansion. These data suggest that LGL might be a subset of effector lymphocytes which may participate to the graft-versus-tumor effect.

Adult↗
PubMed2002

Recovery of lymphocyte and dendritic cell subsets following reduced intensity allogeneic bone marrow transplantation.

Approaches using reduced conditioning regimens have been developed to obtain minimal procedure-related toxicity. Such novel therapeutic options are being explored with good preliminary results concerning feasibility and engraftment. However, many aspects remain under-evaluated and few data are available about immune and dendritic cell (DC) reconstitution after these highly immunosuppressive regimens. We present here our data in 20 patients receiving allogeneic bone marrow transplantation (allo-BMT) using a reduced preparative regimen. We evaluated in the first 3 months following allo-BMT, several immunological parameters including DC subsets, and compared these to historical results obtained in a group of myeloablative allo-BMT patients. We found an early recovery of leukocytes, CD8+ and NK lymphocytes. We also found a trend towards an improved B cell recovery. These results are somewhat in contrast to the altered immune recovery observed in the myeloablative setting. In addition, we found a significant early circulating DC recovery. Circulating blood DCs were also found to be of full donor origin as assessed by FISH in sex-mismatched pairs. Nevertheless, naive CD4 + CD45RA + T cells were found to be profoundly reduced following such regimens.Collectively, these data further enhance the overall benefits of reduced intensity regimens and the need for a stringent biological monitoring for assessment of the potential advantages of reduced intensity allo-BMT in comparison with conventional allo-BMT.

Adult↗
PubMed2001

Hodgkin's disease: prognostic role of gallium scintigraphy after chemotherapy.

Evaluation of the response to therapy is important for optimal selection of treatment strategy in patients with Hodgkin's disease (HD). Refractory disease requires intensive high-dose chemotherapy, whereas unnecessary treatment should be avoided in patients in complete remission. The purpose of this study was to evaluate the contribution of gallium-67 scintigraphy in predicting the clinical outcome in patients with HD and mediastinal involvement on the basis of scan results at the end of chemotherapy. Seventy-four patients with HD and mediastinal involvement were retrospectively investigated with 67Ga scintigraphy 72 h after injection of 220 MBq 67Ga citrate (planar and single-photon emission tomographic studies) following the completion of chemotherapy. At the same time, they all underwent computed tomography (CT). Patients were followed up for an average of 63 months (range 28-124 months). The disease status was newly diagnosed disease in 64 of the patients and relapse in 10. Systemic symptoms were absent (A) in 34 cases and present (B) in 40 cases. Forty-one patients had stage I or II disease and 33 patients had stage III or IV disease. Twenty-two patients had bulky disease on initial diagnosis. At the end of chemotherapy, all 74 patients showed regression of the mass by more than 50% (50%-100%) on CT. Patients were divided into two groups according to the positivity or negativity of the gallium scan after chemotherapy: 61 patients had negative and 13 patients had positive gallium scans. In the gallium-negative group, 19.7% of the patients relapsed and 91.8% were alive at the end of the follow-up. Relapse occurred in 20% of the patients with residual mass and in 19.6% of the patients without residual mass. In the gallium-positive group, 84.6% of the patients had recurrent disease and 61.5% were alive after intensive chemotherapy. There was a statistically significant difference in overall survival between patients with positive and patients with negative gallium results (P=0.0034). Disease-free survival differed significantly between patients with positive and patients with negative gallium scans at the end of chemotherapy (P<0.0001). The relative risk of death was 5.2 and the relative risk of relapse was 11.3 for patients with positive gallium scans, in comparison to those with negative gallium scans. The positive and negative predictive values for predicting relapse were 85% and 87%, respectively. It is concluded that even if gallium scan is performed at the end of chemotherapy, it can predict outcome. Alternative therapy may be required on the basis of gallium scan results obtained after treatment.

Adolescent↗
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

[Thymoma and disseminated lupus erythematosus. Two new cases and review of the literature].

INTRODUCTION: Thymoma is a tumour originating in the epithelial cells of the thymus, associated with several immunologic disorders. The association of thymoma with systemic lupus erythematosus has rarely been described. We report two cases of this association. EXEGESIS: Description of two cases and a review of the literature. Mr T. was 41 years old when the diagnosis of thymoma and lupus was made. The thymectomy did not influence the evolution of his lupus. Mrs G. had been treated because of a lupus for 8 years prior to developing a thymoma. One year later she presented with erythroblastopenia, which was only sensitive to cyclosporin. CONCLUSION: The association between lupus and thymoma has been reported in 36 cases in the literature. Thymoma is benign in 59% of the cases. The clinical presentation of lupus is nonspecific except for age, median 48 years, and sex ratio, 4:3. The clinical outcome of the lupus is not influenced by the thymectomy. Thymoma may precede lupus with a delay of several years or it may be diagnosed concurrently or several years later. This association is not accidental, though the pathogenic link between these conditions remains unknown. One could suppose that the decrease of the thymic function in the course of thymoma could enhance the expression of autoreactive T lymphocytes as well as the activation of B cells. Patients should be followed after thymectomy because autoimmune diseases, particularly lupus, may develop belatedly. On the other hand, thymoma may be suspected mainly when lupus occurs in patients around 50 years of age.

Adult↗