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Vincent Levy

Publications and source records attributed to Vincent Levy.

13 recordsLinked to original sources
PubMed2006

In vivo repopulation ability of genetically corrected bone marrow cells from Fanconi anemia patients.

Fanconi anemia (FA) is a rare inherited genomic instability syndrome representing one of the best examples of hematopoietic stem cell deficiency. Although FA might be an excellent candidate for bone marrow (BM) genetic correction ex vivo, knockout animal models are not sufficient to guide preclinical steps, and gene therapy attempts have proven disappointing so far. Contributing to these poor results is a characteristic and dramatic early BM-cells die-off when placed in culture. We show here that human primary FA BM cell survival can be ameliorated by using specific culture conditions that limit oxidative stress. When coupled with retrovirus-mediated transfer of the main complementation group FANCA-cDNA, we could achieve long-term reconstitution of the stem cell compartment both in vitro and in vivo. Gene-corrected BM cultures grew for >120 days, and after cultured cell transplantation into NOD/SCID mice, clonogenic human cells carrying the FANCA transgene could be detected 6 months after transduction. By comparison, untransduced cells died in culture by 15 days. Of necessity for ethical reasons, experiments were conducted on a very limited number of primary BM cells. By using low cytokine regimen and conditions matching regulatory requirements, a contingent of gene-corrected cells slowly emerges with an unmet potential for in vivo engraftment. Future therapeutic applications of stem cells might be expanding from these data. In addition, we provide a model of gene-corrected human primary cell growth that carries the potential to better delineate the combined role of both DNA damage and oxidative stress in the pathogenesis of FA.

Animals↗
PubMed2006

Prospective evaluation of a polymerase chain reaction-ELISA targeted to Aspergillus fumigatus and Aspergillus flavus for the early diagnosis of invasive aspergillosis in patients with hematological malignancies.

BACKGROUND: Current laboratory and radiological methods for diagnosis of invasive aspergillosis (IA) lack sensitivity and specificity. METHODS: We prospectively evaluated the diagnostic value of twice-weekly screening for circulating Aspergillus fumigatus and A. flavus DNA with a polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA). RESULTS: Among the 201 adult patients with hematological malignancies who were included in the study, 55 IA cases were diagnosed. On the basis of the analysis of 1205 serum samples from 167 patients, the sensitivity, specificity, and positive and negative predictive values of the PCR-ELISA for proven and probable IA cases were 63.6%, 89.7%, 63.6%, and 89.7%, respectively, when samples with 2 consecutive positive results were used. The use of a combination of the PCR-ELISA and a galactomannan (GM) assay increased the sensitivity to 83.3%, increased the negative predictive value to 97.6%, and decreased the specificity to 69.8%. In most patients with IA, PCR-ELISA positivity anticipated or was simultaneous with the initiation of antifungal therapy, the abnormalities found by computed tomography, the mycological/histological diagnosis, and the GM positivity. Overall, 56.3% of the patients had at least 1 positive sample, and the false single-positive rate was 44.8%. CONCLUSIONS: In addition to serial screening for GM antigenemia and radiological surveillance, PCR-ELISA may improve the rates of early diagnosis of IA and the management of patients with hematological malignancies.

Aspergillosis↗
PubMed2006

Factors influencing inclusion of patients with malignancies in clinical trials.

Participation in clinical trials remains low and is a central issue in oncology. The authors identified, through a systematic review, 75 papers published up to August 2004 that report barriers to recruitment of patients in clinical trials. These barriers range from patient preference and concern about information/consent to clinical problems with protocols. Strategies to overcome barriers on the part of patients and clinicians are needed and should be carefully evaluated. Thirty-three (44%) papers reported factors related to patients as influencing the inclusion of patients, 28 (37%) reported clinician's related factors, and 37 (49%) other factors from either specific groups of patients (30 papers, 40%) and/or other scopes (13 papers, 17%). No differences in prevalence were found between papers dedicated to hematologic malignancies and solid tumors. Factors related to clinicians as influential were more frequently reported before 1995 (70%) than thereafter (25%; P = 0.0009). Reporting specific groups of patients as influential was more frequent in North American articles (50%) than in others (14%, P = 0.008). Patients' barriers included mostly patient preference (12 papers), concern about information and/or consent (11 papers), worry about uncertainty (7 papers), and/or relationship with medical team (7 papers). Concerning clinicians, incompatibility of protocol with normal practice (nine papers), problems in complying with the protocol (eight papers), and/or consent procedure (eight papers) were the most reported factors. The remaining factors mostly relied on specific groups of patients (30 papers), notably age of patients (18 papers) and/or minority population (11 papers, all from the USA). Strategies to overcome these barriers are needed and should be carefully evaluated.

Clinical Trials as Topic↗
PubMed2006

Methemoglobinemia and acute hemolysis after tetracaine lozenge use.

Acquired methemoglobinemia is a rare but severe condition associated with oxidizing stressors, most notably medications. Although the symptoms can be life threatening, they usually respond promptly to exposure cessation and methylene blue injection. We describe the first case of methemoglobinemia associated with tetracaine lozenge use. A previously healthy 33-year-old man was admitted with fever, respiratory distress, cyanosis, and acute hemolysis. Physical findings and chest radiograph were normal. Low pulse oximetry readings contrasted with normal partial pressure of oxygen and calculated oxygen saturation. The methemoglobin level was 10.8%. The patient recovered with methylene blue injection and blood transfusions. He reported recent self-medication with tetracaine lozenges for a sore throat during a flu-like illness. No other cause of methemoglobinemia was found.

Acute Disease↗
PubMed2006

Deciphering leukemic B-cell chronic lymphoproliferative disorders.

Diagnosis of leukemic B-cell chronic lymphoproliferative disorders (B-CLPD) is a frequent challenge in hematology. In this multicentric study, we prospectively studied 165 new consecutive leukemic patients with B-CLPD selected on the basis of Royal Marsden Hospital scoring system < or =3. The primary aim of the study was to try to decipher the atypical cases and identify homogenous subgroups. Overall, morphological examination contributed to diagnosis in only 20% cases, all of them CD5 negative. Thirty additional cases were CD5 negative suggestive of leukemic marginal zone lymphoma in most cases. The significantly poorer survival of the 26 cyclin D1 positive cases justifies recommending its systematic determination among atypical B-CLPD. CD20 expression segregated clearly two subgroups among CD5 positive cyclin D1 negative B-CLPD. The 17 patients with the CD20 dim profile represent a homogeneous subgroup very close to typical B-cell chronic lymphocytic leukemia (B-CLL) on morphological, phenotypical and cytogenetical criteria. In contrast, the subgroup of 51 patients with a CD20 bright profile is heterogeneous. Their significantly lower p27 expression level suggest the presence of a proliferative component, underlying a more aggressive disease. Further genomic studies are warranted to establish their precise nature. These cases should not be included in the same therapeutic trials as B-CLL.

Aged↗
PubMed2005

Phase III study of chlorambucil versus fludarabine as initial therapy for Waldenstrom's macroglobulinemia and related disorders.

The WM1 study is a prospective randomized open-label study that includes patients with previously untreated Waldenstrom's macroglobulinemia (WM), splenic lymphoma with villous lymphocytes (SLVL), and nonimmunoglobulin (Ig) M lymphoplasmacytic lymphoma (LPL) who have an indication for treatment. At registration, patients are categorized as having WM, SLVL, or LPL, and these cohorts are to be analyzed separately. The aim of the study is to compare the efficacy of oral chlorambucil at a dose of 8 mg/m(2) (6 mg/m(2) for those > 75 years of age) for 10 days every 28 days to a maximum of 12 cycles with oral or intravenous (I.V.) fludarabine at a dose of 40 mg/m(2) orally or 25 mg/m(2) I.V. (30 mg/m(2)orally or 20 mg/m(2)I.V. for those > 75 years of age) for 5 days every 28 days to a maximum of 6 cycles. Primary endpoints are response to therapy and duration of response; secondary endpoints are improvement in hematologic parameters, toxicity of therapy, quality of life, and survival. To detect a difference in response rate of patients with WM of 15%, assuming that the overall response rates will be 50% to chlorambucil and 65% to fludarabine, with a power of 80%, requires the sample size of each group to be 183, indicating the need for collaboration among a number of national investigator groups. As of February 2005, accrual to the study stands at 143. Registration, randomization, and data collection are entirely Internet-based (www.waldenstroms.org), and the study is organized by an international collaboration, with a planned interim analysis and an external data monitoring committee.

Administration, Oral↗
PubMed2004

[Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma].

Rescue therapies for relapsing/refractory primary central nervous system lymphoma (PCNSL) and intraocular lymphoma (IOL) remain a challenging problem for clinicians. In 2001, we published encouraging results for 22 patients treated at relapse with a CYVE regimen combining high doses of Ara-C (50 mg/m(2)/d in 12 hours infusion dl through d5; 2 g/m(2)/d d2 through d5) and VP16 (200 mg/m(2)/d d2 through d5), followed by intensive chemotherapy based on high doses of thiotepa (250 mg/m(2)/d d-9 through d-7), busulfan (10 mg/kg total dose d-6 through d-4) and cyclophosphamide (60 mg/kg/d, d-3 and d-2 with hematopoietic cell rescue at d0. Patients were enrolled onto the study for a relapse (n = 10; 2 IOL, 3 CSF, 5 brain lesion) or for a refractory disease (n = 12; 9 IOL, 3 brain lesion). CYVE rescue was not administered to patients with refractory IOL who had previously received high doses of methotrexate and Ara-C as part of their first-line treatment. Twenty patients received the intensive chemotherapy and hematopoietic cells rescue. We updated our results in March 2003. Seven patients had neurologic adverse events during the entire procedure. With a median follow up of 6.2 years, the median overall survival is 91 months, and the median survival after intensive chemotherapy has not been reached.

Adult↗
PubMed2004

[Identification of prognostic factors in post-transplantation lymphoproliferative disorders].

Post-transplantation lymphoproliferative disorders (PTLD) represent a severe complication of organ transplantation, so the determination of prognostic factors for the response and the survival is of major interest. Studies on PTLD are hindered by the small number of cases, explaining the conflicting published results. In order to identify, prognostic factors in this kind of disease, 61 patients have been analyzed in a retrospective multicenter study. A new index is proposed to assess the survival probability, it is composed of two factors: the performance status (PS < or = 1 versus 2-3) and the number of involved sites (1 versus > 1). This index seems to be more accurate in PTLD than the IPI, the reference in immunocompetent patients with non Hodgkin lymphomas. However, a similar analysis in a more homogeneous population remains necessary.

Adolescent↗
PubMed2004

Sequential chemotherapy regimens followed by high-dose therapy with stem cell transplantation in mantle cell lymphoma: an update of a prospective study.

This study is a long-term follow-up analysis evaluating clinical outcome of patients with mantle-cell lymphoma treated by the sequential CHOP and DHAP chemotherapy followed by autografting. The median overall survival of 81 months (95% CI, 66-not reached) and the median event free survival of 51 months (95% CI, 43-not reached) confirm the improvement in outcome obtained by such protocol.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Binet's staging system and VH genes are independent but complementary prognostic indicators in chronic lymphocytic leukemia.

PURPOSE: Rai's and Binet's staging systems have contributed significantly to the identification of major prognostic groups in chronic lymphocytic leukemia (CLL), though they fail to accurately predict disease progression at the individual level. Biologic factors, such as the mutational status of the immunoglobulin heavy-chain variable genes (VH, cytogenetics, CD38 expression, and some serum markers, have recently improved prognostic assessment in CLL. In this study, we analyzed the prognostic value of VH mutational status within the different stages of Binet's classification in 145 patients. PATIENTS AND METHODS: Our series consisted of 83 VH mutated (MT) and 62 VH unmutated (UM) patients. MT cases predominated within Binet's stage A (70%), whereas UM cases predominated among stages B and C (62%). RESULTS: Median overall survival (OS) was 84 months for UM patients and was not achieved for the MT group (70% 12-year survival, P <.0001). Concerning Binet's stage A, both median OS and progression-free survival were significantly shorter for UM patients when compared with those of MT patients (97 months v not achieved, P =.0017; and 42 v 156 months, P <.0001), which compared favorably with the classical A' and A" substaging. The VH mutational profile could also segregate stage B and C patients into two groups with different survival patterns (median OS, 78 v 120 months for UM and MT patients, respectively; P =.002). CONCLUSION: The significant survival differences observed between the VH mutational groups, among stage A and stage B and C patients, indicate that Binet's classification and VH genes are independent prognostic variables and are most likely complementary.

Brazil↗
PubMed2002

Identification of prognostic factors in post-transplant lymphoproliferative disorders.

Organ transplantations can lead to post-transplant lymphoproliferative disorders (PT-LPDs) as a result of immunosuppressive therapy. PT-LPDs clearly differ from non-Hodgkin's lymphomas occurring in immunocompetent patients, in terms of clinical presentation, pathological findings and treatment response. Several studies have tried to establish some prognostic factors but the small number of patients hinders the analysis. We studied 61 patients from two transplant centers who developed a PT-LPD after kidney (34 patients), heart (19 patients), lung (4 patients) or liver (3 patients) transplantation. Treatment consisted of modification of the immunosuppressive regimen, chemotherapy and/or monoclonal antibody infusions. Analyzing potential prognostic factors, we found that factors predictive of failure to achieve a complete remission were, in univariate analysis, a performance status (PS) > or =2 and negativity of the tumor for the Epstein-Barr virus (EBV), and in multivariate analysis, only the PS. Factors predictive of lower survival were, in univariate analysis, a PS > or =2, number of sites > 1, primary central nervous system (CNS) location, T-cell phenotype, monoclonality of the tumor, tumor negativity for EBV and chemotherapy as a first treatment; in multivariate analysis, only PS and the number of sites were statistically significant. The International Prognostic Index (IPI) failed to identify a patient subgroup with a lower survival or treatment response, whereas a simple index using PS and number of sites clearly identified three different groups. The median survival has not yet been reached in the lower-risk group, whereas it is 34 months in the intermediate-risk patients and 1 month in the high-risk group. Studies on larger cohorts of patients need to be performed to confirm these data.

Adolescent↗
PubMed2002

High-dose CD34+ cells are not clinically relevant in reducing cytopenia and blood component consumption following myeloablative therapy and peripheral blood progenitor cell transplantation as compared with standard dose.

BACKGROUND: No agreement exists about the number of autologous peripheral blood progenitor cells (PBPCs) to transfuse for optimal hematologic recovery after high-dose chemotherapy. STUDY DESIGN AND METHODS: To determine CD34+ cell dosage following high-dose chemotherapy (in terms of hematologic recovery and blood component consumption), the effects of two schedules of CD34+ cell transfusions in a cohort of patients with myeloma or non-Hodgkin's lymphoma were examined. Forty patients (Group 1) received between 2.5 and 5 x 106 CD34+ cells per kg, with a median of 3.4 x 106 per kg following high-dose chemotherapy, and 40 patients (Group 2), selected to match Group 1 for age, diagnosis, prior therapies, and procedure for PBPC mobilization, received a dose of CD34+ cells >5 x 106 per kg, with a median of 8.4 x 106 per kg (5-33). RESULTS: The median number of days to achieve a neutrophil count of >0.5 x 109 per L and unsupported platelets of >20 x 109 per L was identical for the two groups, but the time required to reach 1.5 x 109 neutrophils per L and 50 x 109 platelets per L was greatly delayed in Group 1. No significant difference was observed for the median number of RBC and platelet transfusions, or for the proportion of patients in each group that did not require either platelet or RBC transfusions. CONCLUSION: Our data confirm a dose-response relationship between CD34+ cell dose transfused and time to hematologic recovery after high-dose chemotherapy. However, the minimal Hb and platelet counts for transfusion independence in the two groups are similar when the CD34+ cell dose is greater than 5 x 106 CD34+ cells per kg. Therefore, our data suggest that it is not necessary to go on with apheresis procedures after 5 x 106 CD34+ cells per kg are harvested to sustain one high-dose chemotherapy.

Adolescent↗