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Biomedical subjects

Y Beguin

Publications and source records attributed to Y Beguin.

At least 19 recordsLinked to original sources

Infections after allogeneic hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen.

Hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning (NMSCT) may be associated with a reduced risk of infection compared to standard allogeneic HCT. We retrospectively analyzed incidence and risk factors of infection in 62 patients undergoing NMSCT with low-dose TBI +/- fludarabine and postgrafting CsA and MMF. The proportion of patients with any infection was 77%, but the majority of infectious events occurred beyond day 30. Donor other than sibling, older age, early disease and male gender were significant risk factors. The incidence of bacteremia was 55% at 1 year and the number of bacteremic episodes was 0.9 per patient (0.08 before day 30). The risk of bacteremia increased with older age and the use of a donor other than an HLA-identical sibling, but not with neutropenia. The incidence of infections other than bacteremia correlated with the use of corticosteroids. The risk of CMV infection increased with high-risk CMV serology, and risk of CMV disease with high-risk CMV serology, older age, first transplantation and a diagnosis of lymphoma. In conclusion, after NMSCT, infections are not frequent in the first 30 days post transplant but careful long-term monitoring is necessary thereafter.

Adrenal Cortex Hormones↗

[Nonmyeloablative stem cell transplantation as cancer immunotherapy].

Allogeneic hematopoietic stem cell transplantation (HSCT) is used for the treatment of selected haematological malignancies. Its curative potential is based on two different mechanisms, i.e. the conditioning regimen and the graft-versus-host immunologic reactions. However, because of its toxicity, it is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols. These transplants are called nonmyeloablative HSCT or minitransplants. These are feasible with a relatively low transplant-related mortality even in patients up to 70 years. In addition, strong anti-tumor responses are observed in several haematological malignancies.

Hematologic Neoplasms↗

[Clinical evaluation of 23 children with neuroblastoma. The experience of a single institution].

In this retrospective study, we analyse epidemiology, clinical symptoms and therapeutic results in a group of 23 children with neuroblastoma. Half of them were less than 2 years of age; in 19 of 23, the primitive tumour was abdominal; 35% of them were initially metastatic. The overall survival was 83% at 5 years and the event free survival, 75% at 5 years. Pronostic factors are age, extension of the disease at diagnosis, biologic parameters and genetic study of the neuroblast cells (amplification of N-myc oncogen). Our study shows the deleterious effect of bone lesions.

Abdominal Neoplasms↗

Bacteremia after hematopoietic stem cell transplantation: incidence and predictive value of surveillance cultures.

UNLABELLED: We studied 622 transplants undertaken between 1982 and 2001 to: (1) determine the incidence, timing and etiology of bacteremias, and (2) examine the ability of routine surveillance cultures to predict bacteremias. A total of 404 episodes (0.65 episode per patient) occurred in 248 patients, due to coagulase-negative staphylococci (n=171, 42%), Gram-negative bacteria (n=129, 32%), streptococci (n=48, 12%), other Gram-positive bacteria (n=33, 8%), anaerobes (n=9, 2%) and fungi (n=14, 3%). Bacteremias were more frequent in allogeneic (0.96 episode/patient) compared to autologous (0.44) transplants (P<0.0001). The overall incidence decreased from 0.92 episode/patient until 1990 to 0.66 in 1991-1996 and 0.55 in 1997-2001 (P<0.0001), but this was only observed in autologous transplants. Among them, 212 (53%) occurred before hospital discharge and 192 (47%) thereafter. This proportion was lower for coagulase-negative staphylococci, other Gram-positive bacteria and Gram-negative bacteria compared to other agents (P=0.001). In 50% of the cases, the agent responsible for the bacteremic episode was present in routine surveillance cultures previously. IN CONCLUSION: (1) bacteremias remain a frequent complication, particularly in allogeneic transplantation, even long after hospital discharge; (2) routine surveillance cultures can predict bacteremias in 50% of the cases, but the practical impact of this observation is limited in view of the costs.

Adolescent↗

Haematopoetic stem cell transplantation for refractory autoimmune cytopenia.

This study describes the outcome of patients receiving haematopoietic stem cell transplantation (HSCT) to treat severe refractory autoimmune cytopenia. The registry of the European Group of Blood and Marrow Transplantation holds data on 36 patients receiving 38 transplants, the first transplant was autologous for 27 and allogeneic for nine patients. Patients had autoimmune haemolytic anaemia (autologous: 5; allogeneic: 2), Evans's syndrome (autologous: 2; allogeneic: 5); immune thrombocytopenia (autologous: 12), pure red cell aplasia (autologous: 4; allogeneic: 1), pure white cell aplasia (autologous: 1; allogeneic 1), or thrombotic thrombocytopenic purpura (autologous: 3). Patients had longstanding disease having failed multiple prior treatments. Among 26 evaluable patients mobilized for autologous HSCT, three died of treatment-related causes, one died of disease progression, seven were non-responders, six patients had transient responses and nine had continuous partial or complete remission. Of the seven evaluable patients receiving allogeneic HSCT, one died of treatment-related complications, one with transient response died of progressive disease and five had a continuous response. Autologous and allogeneic HSCT may induce a response in a subset of patients with autoimmune cytopenia of long duration albeit at the price of considerable toxicity.

Adolescent↗

PET scan imaging in oncology.

With the emergence of positron emission tomography (PET) from research laboratories into routine clinical use, it is important to redefine the most appropriate use of each imaging technique. The aim of this review article is to show the potential of PET in oncology. We discuss the most promising indications and the perspectives for the future. We will also point out the shortcomings and the important questions to be answered before fully considering PET as a necessary tool in the day-to-day practice of oncology. Although many studies have documented the high accuracy of 18F-FDG PET for the detection and staging of malignant tumours and for the monitoring of therapy results in these patients, it is very important to assess the impact of the technique on patient outcome and to show cost-effectiveness from the societal viewpoint.

Fluorodeoxyglucose F18↗

Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC.

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.

Adult↗

Early detection of relapse by whole-body positron emission tomography in the follow-up of patients with Hodgkin's disease.

BACKGROUND: Relapse after treatment of Hodgkin's disease (HD) is usually identified as a result of the investigation of symptoms. We undertook this study to examine the value of whole-body positron emission tomography (PET) for the detection of preclinical relapse. PATIENTS AND METHODS: Thirty-six patients underwent 2-[fluorine-18]fluoro-2-deoxy-D-glucose ((18)F-FDG) PET at the end of treatment and than every 4-6 months for 2-3 years after the end of polychemotherapy and/or radiotherapy. In those cases of abnormal (18)F-FDG accumulation a confirmatory study was performed 4-6 weeks later. RESULTS: One patient had residual tumor and four patients relapsed during a follow-up of 5-24 months. All five events were correctly identified early by (18)F-FDG PET. Residual tumor or relapse was never first diagnosed based on clinical examination, laboratory findings or computed tomography (CT) studies. Two patients presented B symptoms and the three others were asymptomatic at the time of residual disease or relapse. Confirmation of residual disease or relapse was obtained by biopsy in four patients 1, 1, 5 and 9 months after PET and by unequivocal clinical symptoms and CT studies in one patient 3 months after PET. False-positive (18)F-FDG PET studies incorrectly suggested possible relapse in six other patients, but the confirmatory PET was always negative. Our study also provides important information about physiological (18)F-FDG uptake in the thymus. CONCLUSIONS: Our data suggest the potential of (18)F-FDG PET to detect preclinical relapse in patients with HD. This could help identify patients requiring salvage chemotherapy at the time of minimal disease rather than at the time of clinically overt relapse. Further studies are warranted to determine the impact of PET on treatment management and outcome. In fact, the aim of follow-up procedures is not only to detect preclinical relapse but mainly to obtain better results by starting salvage treatment earlier. A cost-benefit analysis will also be necessary before (18)F-FDG PET can be used routinely in the follow-up of patients with HD.

Adolescent↗

[How I treat...chronic myeloid leukemia].

This review article describes the identification of the tyrosine kinase BCR/ABL as the hallmark of chronic myeloid leukemias (CML) as well as the development of a specific inhibitor of this tyrosine kinase, the STI571 (Glivec, imatinib mesylate). The authors discuss the results of a phase I and three phase II trials reporting the efficacy of STI571 as treatment for CML patients and propose two simplified algorithms that may help to guide decision-making for the individual patient.

Algorithms↗

Barotrauma-induced tension pneumoperitoneum.

We report the case of a massive tension-pneumoperitoneum developing immediately after starting mechanical ventilation (barotrauma). Careful analysis of CT-data provided meaningful informations in assessing the non surgical pulmonary source of pneumo peritoneum.

Barotrauma↗

Erythropoiesis after nonmyeloablative stem-cell transplantation is not impaired by inadequate erythropoietin production as observed after conventional allogeneic transplantation.

BACKGROUND: It is now well established that after conventional allogeneic hematopoietic stem-cell transplantation (HSCT), erythropoietic recovery is impaired because erythropoietin (Epo) production remains inadequate for prolonged periods of time. However, erythropoietic reconstitution after nonmyeloablative SCT (NMSCT) has never been characterized. METHODS: Twelve patients received a nonmyeloablative conditioning regimen consisting of 2 Gy total body irradiation (TBI) alone (n=6), 2 Gy TBI and fludarabine (n=3), or cyclophosphamide and fludarabine (n=3), followed by transplantation of allogeneic peripheral blood stem cells. Graft-versus-host-disease (GvHD) prophylaxis was carried out with mycophenolate mofetil (from day -1 to day 28) plus cyclosporine (from day -1 to day 120 or longer in case of chronic GvHD). Erythropoiesis was quantitated by soluble transferrin receptor (sTfR) levels, and the adequacy of Epo production was evaluated by the observed-to-predicted Epo ratio (O/P Epo). RESULTS: Mean sTfR levels decreased following the conditioning regimen but remained well within the normal range throughout the posttransplant period. The O/P Epo ratio presented an initial surge quite similar to that observed after conventional conditioning. Thereafter, the O/P Epo ratio normalized rapidly, and Epo levels remained adequate during the whole observation period. CONCLUSION: Contrarily to what is observed after myeloablative transplant, Epo levels remained adequate after NMSCT, resulting in normal erythropoiesis. These results suggest that the administration of erythropoietin therapy (rHuEpo) could be less effective after NMSCT than after conventional allogeneic transplant.

Adult↗

Changing pattern of bacterial susceptibility to antibiotics in hematopoietic stem cell transplant recipients.

UNLABELLED: Adequate infection prophylaxis and empirical antibiotic therapy are of critical importance after hematopoietic stem cell transplantation (HSCT). We examined the evolution of bacterial susceptibility to antibiotics in 492 patients (198 allografts and 294 autografts) transplanted between 1982 and 1999 and evaluated whether ciprofloxacin prophylaxis and an empirical antibiotic regimen (glycopeptide + third-generation cephalosporin) were still valid. We collected all susceptibility tests performed during the initial hospitalization on blood cultures as well as routine surveillance cultures and analyzed susceptibility to ciprofloxacin and to major antibiotics used in our unit. Gram-positive cocci rapidly became resistant to ciprofloxacin (susceptibility around 70% in 1990 to less than 20% in 1998) but sensitivity to glycopeptides remained unaltered. There was a rapid decline in the number of patients colonized with Gram-negative bacilli in the early years of ciprofloxacin prophylaxis. However, susceptibility to ciprofloxacin fell sharply from around 90% in 1990 to around 30% in 1999. In parallel, susceptibility to ceftazidime also decreased to less than 80% in recent years. Piperacillin (+/- tazobactam) did not show any variation over time and its efficacy remained too low (about 60%). Imipenem as well as recently introduced cefepim and meropenem showed stable and excellent profiles (>90% susceptibility). IN CONCLUSION: (1) quinolone prophylaxis has now lost most of its value; (2) the choice of a third-generation cephalosporin for empirical antibiotic therapy may no longer be the best because of the emergence of Gram-negative strains resistant to beta-lactamases, such as Enterobacter sp. More appropriate regimens of empirical antibiotic therapy in HSCT recipients may be based on the use of a carbapenem or fourth-generation cephalosporin.

Anti-Bacterial Agents↗

Preemptive cellular immunotherapy after T-cell-depleted allogeneic hematopoietic stem cell transplantation.

GVHD is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is due to donor lymphocytes that are cotransplanted with donor stem cells. These donor lymphocytes are primed by histocompatibility differences between donors and recipients and activated by a cytokine storm caused by the conditioning regimen. The most efficient method for prevention of GVHD consists of T-cell depletion (TCD) of the graft. However, TCD usually leads to an increased risk of leukemia relapse because of the loss of the graft-versus-leukemia (GVL) effect. Several groups have studied the feasibility of preemptive donor lymphocyte infusion (DLI) to lessen the impact of TCD on leukemia relapse. Preemptive DLI is given several weeks to months after the transplantation, ie, after the cytokine storm and after the patient has recovered from conditioning-regimen-related toxicities. After briefly discussing various techniques of TCD of the graft and the efficacy of DLI, this article reviews the first clinical studies evaluating a strategy of TCD of the graft followed by preemptive DLI.

Graft vs Host Disease↗

Nonmyeloablative allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment for selected hematological malignancies. Its curative potential is largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols (nonmyeloablative stem cell transplantation or NMSCT) based on a two-step approach: first, the use of immunosuppressive (but nonmyeloablative) preparative regimens providing sufficient immunosuppression to achieve engraftment of allogeneic hematopoietic stem cells and, in a second step, destruction of malignant cells by the GVL effect. Preliminary results showed that NMSCT were feasible with a relatively low transplant-related mortality (TRM), even in patients older than 65 years. In addition, strong antitumor responses were observed in several hematological malignancies as well as in some patients with renal cell carcinoma. After discussing the mechanisms and efficacy of the GVL effect as well as the rationale for NMSCT strategies, this article reviews the first results of ongoing clinical trials. Innovative modalities that may permit amplification of the GVL effect while minimizing the risk of GVHD are discussed. Because the benefits of NMSCT over alternative forms of treatment remain to be demonstrated, this strategy should be restricted to patients included in clinical trials.

Hematologic Neoplasms↗