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Stéphane Depil

Publications and source records attributed to Stéphane Depil.

8 recordsLinked to original sources
PubMed2005

Peptide-binding assays and HLA II transgenic Abeta degrees mice are consistent and complementary tools for identifying HLA II-restricted peptides.

The identification of MHC class II-restricted peptides has become a priority for the development of peptide-based prophylactic and therapeutic vaccines. The aim of this study was to assess the correlations between peptide-binding assays on purified HLA II molecules and immunization of human HLA II transgenic mice deficient in murine class II molecules (Abeta degrees ). We used as models two MHC class II-restricted peptides, one derived from the HIV Nef regulatory protein (Nef (56-68)) and the other from the Schistosoma mansoni 28-kDa glutathione-S-transferase (Sm28GST (190-211)). High correlations were found between the two approaches, which showed that the Nef (56-68) and Sm28GST (190-211) peptides may represent promiscuous ligands for HLA-DQ and for HLA-DR molecules, respectively. We suggest a rational method based on the combination of peptide-binding assays and HLA II transgenic mice experiments as consistent and complementary tools for selecting T helper epitopes.

Amino Acid Sequence↗
PubMed2005

Outcome of patients less than 55 years of age with high-risk acute leukemia who did not have an human leukocyte antigen-identical related donor: a long-term study of 97 consecutive patients.

Between January 1993 and December 2000, an unrelated donor search (UDS) was initiated for 97 consecutive patients [46 acute lymphoblastic leukemia (ALL) and 51 acute myeloid leukemia (AML)]. Leukemia was considered to be of poor prognosis in cases of refractory disease (n=70), unfavourable karyotype (n=22) or miscellaneous (n=5). All patients had previously received various chemotherapies and 9 had undergone an autologous stem cell transplantation (SCT). The median age at UDS initiation was 25 (range 2.7-55) years. The median time to identify a suitable living donor or cord blood (CB) was 60 days. Eventually, 33 patients received unrelated allo-SCT (including 9 CB), 12 auto-SCT, 39 chemotherapy and 13 palliative treatment. At a median of 54 months, 18 patients were alive, including 15 in remission. The 4-year overall survival rates were 32%, 37%, 15% and 0% for allo-SCT, auto-SCT, chemotherapy or palliative treatment, respectively. Patients who received either allo- or auto-SCT had better survival than those who did not (P<0.0001). For ALL, only allo-SCT significantly improved survival (P<0.007). Finally, patients who received allo-SCT died less often of relapse than patients who did not (P<0.0001). Unrelated allo-SCT gives a substantial long-term survival and cure in patients with high-risk acute leukemia. For patients who achieve remission and for whom UDS fails, auto-SCT may prove to be a good approach. For patients who fail to enter into remission, intensive salvage chemotherapy has a very limited effect.

Adolescent↗
PubMed2004

Impact of Small Bowel Exploration Using Video-Capsule Endoscopy in the Management of Acute Gastrointestinal Graft-versus-Host Disease.

BACKGROUND: The purpose of this study was to evaluate the impact of the global diagnostic approach on the outcome of patients suspected of having acute (a) gastrointestinal (GI) graft-versus-host disease (GVHD). METHODS: Ten consecutive patients with suspected aGI-GVHD were prospectively explored with an exhaustive approach including video-capsule endoscopy (VCE). Images observed with VCE were compared with results obtained with other GI investigations including duodenal biopsies. RESULTS.: Five patients had a normal VCE examination: four were successfully treated symptomatically, but one died as a result of toxoplasmosis. VCE disclosed aGI-GVHD lesions in all five remaining patients, and two of the five were considered normal by upper GI endoscopy. All of these patients experienced improvement in their GI symptoms within 2 weeks of adjustments to their immunosuppressive treatment. CONCLUSIONS: This approach has enhanced the authors' ability to adapt immunosuppressive treatments in patients suffering from suspected aGI-GVHD. Further investigation of the apparently high negative predictive value of VCE will be of great interest, particularly with a view to avoiding unnecessary immunosuppressive treatment.

Acute Disease↗
PubMed2004

Efficient generation of antileukemic autologous T cells by short-term culture and gamma-irradiation of myeloid leukemic cells.

Blasts from patients with acute myeloid leukemia (AML) can be differentiated in dendritic cells (DCs) using appropriate combinations of cytokines. However, generation of autologous antileukemic cytotoxic T cells using leukemic DCs remains difficult. We have previously reported that expression of costimulatory molecules in cultured AML cells could be induced by gamma-irradiation. In the present study, blasts from 21 patients with AML were cultured in vitro for 2 days, then cells were gamma-irradiated and antigen-presenting cell (APC) characteristics were assessed. gamma-Irradiation induced expression of several characteristics of APCs in AML blasts, including expression of CD80, CD86, and BDCA-4, and were stimulators of allogeneic mixed lymphocyte reactions. Autologous antileukemic cytotoxicity was induced in seven out of ten cases. This study shows that cells with APC characteristics and able to induce ex vivo stimulation of autologous antileukemic T cells can be generated from AML cells using the simple and rapid method of gamma-irradiation of cultured leukemic cells.

Acute Disease↗
PubMed2003

Chemotherapy increases transgene expression in leukemic cells.

BACKGROUND: Patients with acute myeloid leukemia (AML) often obtain complete remission with chemotherapy but the majority of patients relapse. Combining chemotherapy and gene therapy appears to be a promising approach; however, the effects of chemotherapy on transgene expression in leukemic cells have not yet been investigated. METHODS: DA1-3b leukemic cells were transfected with pCDNA3 plasmids carrying GM-CSF or LacZ cDNA. The leukemic K562 cell line and primary cultured AML cells were transduced with an Ad5.CMV-LacZ adenoviral vector. Cells were then incubated with various concentrations of daunorubicin (DNR) and cytosine arabinoside (Ara-C), and expression of the transgene was measured. Murine DA1-3b-pCDNA3/LacZ leukemic cells were also injected into syngeneic C3H/Hej mice. RESULTS: In the cells carrying pCDNA3, DNR and Ara-C dramatically increased expression of the LacZ and GM-CSF transgenes. Over-expression depended on drug dose and was due to increased transcription. Enhancement was also observed in K562 cells and in some primary cultured AML samples transduced with the Ad5.CMV-LacZ adenovirus. Addition of N-acetyl-L-cysteine inhibited the over-expression, suggesting that reactive oxygen species were involved in activating the CMV promoter. In the A549 lung carcinoma cell line transduced with Ad5.CMV-LacZ, Ara-C had only a minor effect, and DNR had a detrimental effect, suggesting that expression depends on cell type. In vivo experiments in which mice received DA1-3b-pCDNA3/LacZ leukemic cells, and were then treated with Ara-C, also showed increased transgene expression in these leukemic cells. CONCLUSIONS: In leukemic cells, chemotherapeutic agents can induce over-expression of transgenes. This suggests a promising combined strategy for the treatment of acute leukemia.

Acute Disease↗
PubMed2002

Primary central nervous system lymphoma in immunocompetent adults: poor results mainly associated with high treatment related toxicities.

Treatment of primary central nervous system lymphoma (PCNSL) occurring in immunocompetent patients remains controversial but long-term survival has been reported in patients treated by chemotherapy regimens containing non-lipophilic drugs. We report 34 consecutive PCNSL patients treated at our institution by a chemotherapy regimen that combined drugs crossing and not crossing the blood-brain barrier. Early toxicity was high as 10 of 17 deaths that occurred within the first year of diagnosis were treatment related. Infections and thromboembolism were the main causes of toxicity. We concluded that the use of drugs of uncertain efficacy in these particularly fragile patients is questionable.

Aged↗