[Buried chipped skin grafts for patients in failure of treatment]. / Procédé de greffes enfouies en situation d'échecs d'autogreffes cutanées.

Local conditions can lead to a failure of traditional skin grafts. We propose here our technique about the realization of autologous skin graft using it buried chipped grafts, for wounds in failure of treatments or at risk of failure. The protocol includes cutting the skin graft within little squared pieces of a few millimeters of length, that are then buried directly deep into the wound. We can then obtain little islands of epidermisation on the random places of the wound that will heal by confluence of those epidermal islands.

Incidence and risk factors of hypoxaemia after preoxygenation at induction of anaesthesia.

BACKGROUND: The incidence of hypoxaemia related to airway management is still a matter of concern. Our aim was to determine the factors that contribute to hypoxaemia during induction of anaesthesia after a standardised preoxygenation procedure. METHODS: The study was a multicentre and prospective observational trial. It evaluated the incidence of hypoxaemia at induction of anaesthesia in adult patients. The primary endpoint was the incidence of hypoxaemia defined as pulse oximetry of arterial oxyhaemoglobin saturation (SpO2) <95%. RESULTS: Of 2398 patients, hypoxaemia was observed in 158 (6.6%). We identified five preoperative independent risk factors: chronic obstructive pulmonary disease, hypertension, anticipated difficult mask ventilation and difficult tracheal intubation, and emergency surgery. There were also three pre-induction independent risk factors: difficult preoxygenation, difficult mask ventilation, and difficult tracheal intubation. We found a high negative predictive value of preoperative risk factors for difficult mask ventilation of 0.96 (0.95-0.96), and for difficult tracheal intubation (0.95 [0.94-0.96]). A total of 723 patients (30%) experienced difficult preoxygenation (FeO2 <90% at the end of preoxygenation). Male sex, chronic obstructive pulmonary disease, hypertension, emergency surgery, and predictable difficult mask ventilation were independent patient risk factors for difficult preoxygenation. CONCLUSIONS: Difficult mask ventilation and difficult tracheal intubation are risk factors for hypoxaemia at induction of general anaesthesia. Difficult preoxygenation was observed in 30% of patients and was also identified as a risk factor for hypoxaemia. This suggests that techniques improving preoxygenation should be implemented in daily practice.

Inclusion of patients with acute leukemia in clinical trials: a prospective multicenter survey of 1066 cases.

BACKGROUND: to estimate the prevalence of adults and children with acute leukemia (AL) included in clinical trials and to determine factors associated with noninclusion. PATIENTS AND METHODS: all patients with AL admitted to the 17 departments managing AL in Paris area from 2005 to 2007 were prospectively included. Clinical data, therapeutic decisions, and enrollment in trials were recorded. Reasons that prevented accrual were identified. RESULTS: a total of 1066 admissions with AL (85% of adults) were recorded, and 34 trials were open. In adults, the rate of inclusion in a trial was 25% [95% confidence interval (CI) 21% to 28%] for acute myeloid leukemia (AML) and 23% (95% CI 17% to 29%) for acute lymphoid leukemia (ALL). In children, the rate of inclusion was 58% (95% CI 41% to 73%) for AML and 64% (95% CI 55% to 72%) for ALL. The rate of inclusion varied across centers, with a significant increase when they were involved in clinical research. Patients included in trials differed significantly from those not included according to age, primary/secondary AL, leukemia type, results of cytogenetic analyses, and stage of disease. CONCLUSIONS: the rate of inclusion is higher than in oncology. This difference may be explained by management in specialized centers often involved in clinical research.

Classic and Non-Classic Effects of the Duration of Supplementation of 25-Hydroxicholecalciferol in Broiler Chicken Diets.

The present study aimed to determine the effect of different times of supplementation of 25-hydroxycholecalciferol (25(OH)D3) in broiler chickens on the performance, carcass and cuts yield, bone resistance, plasma concentration of 25(OH)D3, and expression of the mTOR gene. The treatments were a control diet (CD) supplemented with 3000 IU vitamin D3/kg of feed from 1 to 46 d, or the CD + 2760 IU (69 mcg) of 25(OH)D3/kg of feed from 1 to 21 d, from 1 to 35 d, or from 1 to 46 d. The period of supplementation of 25(OH)D3 did not affect the growth performance of broilers, but the breast meat yield was linearly increased in response to increasing days of supplementation (p < 0.05). Birds supplemented with 25(OH)D3 at the time of the analysis showed an increase (p < 0.05) in the plasma concentration of 25(OH)D3 when compared to non-supplemented birds. The mTOR gene expression (p < 0.05), and breast protein deposition (p < 0.05) presented a quadratic response related to the supplementation period of 25(OH)D3. The fat content of the breast linearly decreased (p < 0.05) as the period of supplementation was extended. The results also showed a positive linear correlation between mTOR expression and 25(OH)D3 plasma levels (r = 0.593; p < 0.05).

Influence of Enzyme Supplementation in the Diets of Broiler Chickens Formulated with Different Corn Hybrids Dried at Various Temperatures.

We evaluated the influence of enzymatic supplementation on the growth performance and cecal microbiota of broilers. A total of 2160 1-day-old male chicks were used in a 3 × 2 × 2 factorial arrangement (three corn hybrids, two drying temperatures -80 and 110 °C, with or without the inclusion of an enzymatic blend (amylase, xylanase, and protease) (20 birds/pen, n = 9). For all performance and digestibility parameters, we observed, in general, isolated effects of the corn hybrids and drying temperature. Birds that received the enzymatic blend in the diet showed better weight gain from 1 to 21 days (d) and better digestibility coefficients of nutrients at 42 d. Birds fed diets with corn dried at 80 °C showed a better feed conversion ratio from 1 to 42 d. At 21 d of age, enzymatic supplementation had positive effects on jejunum morphology. Enzyme supplementation increased the abundance of the phylum Tenericutes, class Bacilli and Mollicutes, reduced Clostridia, and increased the abundances of the families Lactobacillaceae, Anaeroplasmataceae, and O_RF39;F. In conclusion, the addition of amylase, xylanase, and protease led to a better nutrient digestibility, performance, and intestinal morphology. In addition, enzyme supplementation changed the diversity, composition, and predicted function of the cecal microbiota at d 21.

Different enzymatic associations in diets of broiler chickens formulated with corn dried at various temperatures.

The effect of supplementation of different enzymatic associations in the feed of broiler chickens formulated with corn dried at 80°C or 110°C on growth performance and carcass yield was evaluated. In addition, the influence of the different enzymatic associations on the cecal microbiota was studied. One-day-old male broiler chicks (1,320) were distributed in a completely randomized design in a 2 × 5 factorial arrangement (6 replicates; 22 birds/replicate). The treatments were 2 corn drying temperatures (80°C and 110°C) and 5 diets. The diets consisted of a positive control (PC), a negative control (NC) with a reduction of 100 kcal/kg of apparent metabolizable energy, and 3 enzyme combinations added to the NC diet: amylase, amylase + xylanase, and amylase + xylanase + protease. The feed conversion ratio (FCR) from 1 to 7 d of chickens fed diets formulated with corn dried at 80°C was better (P = 0.045) than that of chickens fed diets dried at 110°C. Regardless of the enzymatic association, the supplementation improved body weight gain (P = 0.01) of the NC group to the same level as the PC group. The FCR of the NC was similar to that of the PC only when the 3 enzymes were included from 1 to 21 d (P = 0.001) and regardless of the enzymatic association for the period from 1 to 42 d (P = 0.007). Regarding cecal microbiota, the alpha diversity was similar among the groups (P > 0.05). The beta-diversity analysis showed that the microbiota of the birds receiving the combination of the 3 enzymes was similar to that of birds fed the PC diet (P = 0.18; R = 0.074), with a similar effect observed for the predicted metabolic functions (Linear discriminant analysis effect size). In conclusion, chickens fed diets formulated with corn dried at 80°C had better FCR during the prestarter phase. The enzymatic supplementation improved the FCR of the birds, which may partially be explained by the modulation of the cecal microbiota.

High doses of phytase on growth performance, bone mineralization, diet utilization, and plasmatic myo-inositol of turkey poults.

An experiment was conducted to evaluate the growth performance, bone mineral composition, diet utilization, and plasmatic concentration of myo-inositol (MYO) in turkeys fed different phytase doses from 1 to 28 d. A total of three hundred and twenty 1-day-old turkeys were distributed in a completely randomized design with 4 treatments and 8 replicates of 10 birds each. Treatments included a basal diet without phytase; reduced diet (reduced -0.15% available P and -0.18% Ca) without phytase; reduced diet + 2,000 units of phytase (FYT)/kg; and reduced diet + 4,000 FYT/kg. From day 26 to 28, partial excreta collection was conducted, and on day 28, 7 birds per replicate were euthanized for collection of ileal content and left tibia bones were removed from 2 of the same euthanized birds. Feed, excreta, and ileal digesta samples were analyzed to determine nutrient digestibility and metabolizability, ileal digestible energy, and AME. Tibia bones were analyzed for ash, Ca, and P content, and calculation of Seedor index. On day 28, blood samples were collected from 2 turkeys per replicate to analyze plasmatic MYO concentration. Feed conversion ratio was not affected, but phytase supplementation resulted in higher feed intake and body weight gain compared to turkeys fed the reduced diet (P < 0.05), and both doses were similar to the basal diet. Increasing the phytase dose had a linear effect (P < 0.05) on ileal digestibility of P and metabolizability of DM, CP, Ca, and Na, and also on AME. P content in the tibia bone increased linearly (P < 0.05) with phytase supplementation, and the same linear increase (P < 0.05) was observed for plasmatic MYO. In conclusion, the supplementation of turkey poult's diets with high levels of phytase up to 4,000 FYT/kg improves diet utilization by increasing P digestibility and dietary metabolizability, leading to higher P content in the bone and enhancing MYO provision and absorption.

Effect of different doses of phytase and protein content of soybean meal on growth performance, nutrient digestibility, and bone characteristics of broilers.

This study evaluated the effects of high phytase doses and soybean meal (SBM) with different CP content on growth performance, ileal nutrient digestibility, digestible energy, plasmatic myo-inositol, phosphate release in vitro, and bone composition of broiler chickens. One thousand two hundred 1-day-old broilers were distributed in a 2 × 2 completely randomized factorial arrangement, with 2 phytase doses (1,000 and 2,500 phytase units [FYT]/kg of feed) and 2 SBM with different CP concentrations (45 and 47%), totaling 4 treatments with 12 replicates of 25 birds each. The chickens received feed and water ad libitum. Diets were based on corn and SBM, with different inclusions of soybean hull used to dilute the CP content of SBM according to each treatment. The inclusion of 2,500 FYT increased weight gain from 0 to 21 d (P < 0.05), whereas growth performance from 22 to 42 d was not affected, and SBM had no effect on growth performance. At day 21, ileal digestibility of dry matter, ash, and P, and digestible energy were greater in diets with 2,500 FYT/kg (P < 0.05), as well as phosphate in vitro release (P < 0.01) compared to the lower dose. At day 42, diets with SBM 47% CP and 2,500 FYT/kg promoted greater digestibility of dry matter, ash, CP, Ca, P, and digestible energy (P < 0.001), and greater phosphate release (P < 0.05) in comparison to other treatments. myo-inositol level in the plasma at 21 and 42 d was higher with the use of 2,500 FYT compared to 1,000 FYT (P < 0.05). The higher phytase dose increased tibia ash, toe ash, and Seedor Index (P < 0.05) at day 21, and the Ca content in tibia was higher with 2,500 FYT and SBM 47% CP at day 42. In conclusion, higher phytase doses for broilers improve weight gain, myo-inositol provision, and bone mineral composition. Nutrient ileal digestibility can be enhanced by higher phytase doses when in combination with SBM of greater nutritional quality.

Analysis of the foveal microvasculature in sickle cell disease using swept-source optical coherence tomography angiography.

Ischemic microangiopathy was clearly identified in sickle cell disease (SCD) using fluorescein angiography. A prospective observational clinical study was conducted to assess the foveal avascular zone (FAZ) area and explore perifoveal microvasculature changes in the superficial (SCP) and deep (DCP) capillary plexus using optical coherence tomography angiography (OCTA) and compare two genotypes-HbS/HbS (HbSS) and HbS/HbC (HbSC)-to control. All consecutive patients with electrophoretic confirmation of SCD were included. Swept-source OCTA scans (Triton Plus, Topcon, Tokyo, Japan) with a 3 × 3-mm scanning area and ultra-wide field (UWF) retinography (California, Optos, Fife, Scotland) were recorded for all patients. For OCTA analysis, preset parameters were used to segment the SCP and DCP. The FAZ area was manually assessed. The number of vascular branching points was automatically assessed based on the vascular skeletonization using ImageJ software. Eyes were staged based on Goldberg's classification of SCD retinopathy (SCDR) using UWF imaging. Forty-six eyes of 24 patients were included in the HbSS (n = 27) and HbSC (n = 19) groups and 16 eyes of 8 unaffected patients in a control group. In the DCP, the FAZ was significantly larger in the HbSC (p = 0.0001) and HbSS (p = 0.0004) groups compared to controls. The FAZ area in the SCP, CRT and number of superficial vascular branching points did not significantly differ between both genotypes. There were less branching points in the HbSC (p = 0.034) and HbSS (p = 0.0014) groups than in controls. The Goldberg stage was significantly higher in the HbSC group than in the HbSS group (2.21 vs. 1.22, p = 0.0062). OCTA provides useful information on macular microvasculature and structural alterations associated with SCDR. Ischemic abnormalities are more predominant in the DCP in case of SCDR and no difference was found between genotypes of patients visually asymptomatic.

Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours.

Everolimus displays antiproliferative effects on cancer cells, yields antiangiogenic activity in established tumours, and shows synergistic activity with paclitaxel in preclinical models. This study assessed the safety and the pharmacokinetic interactions of everolimus and paclitaxel in patients with advanced malignancies. Everolimus was dose escalated from 15 to 30 mg and administered with paclitaxel 80 mg m(-2) on days 1, 8, and 15 every 28 days. Safety was assessed weekly, and dose-limiting toxicity (DLT) was evaluated in cycle 1. A total of 16 patients (median age 54.5 years, range 33-69) were entered; 11 had prior taxane therapy for breast (n=5), ovarian (n=3), and vaginal cancer (n=1) or angiosarcoma (n=2). Grade 3 neutropenia in six patients met the criteria for DLT in two patients receiving everolimus 30 mg weekly. Other drug-related grade 3 toxicities were leucopenia, anaemia, thrombocytopenia, stomatitis, asthenia, and increased liver enzymes. Tumour stabilisation reported in 11 patients exceeded 6 months in 2 patients with breast cancer. Everolimus showed an acceptable safety profile at the dose of 30 mg when combined with weekly paclitaxel 80 mg m(-2), warranting further clinical investigation.

Analysis of factors influencing inclusion of 102 patients with stage III/IV Hodgkin's lymphoma in a randomized trial for first-line chemotherapy.

BACKGROUND: Data on factors influencing inclusion of Hodgkin's lymphoma (HL) patients in randomized clinical trials (RCT) are limited and, for the present study they were analyzed in a RCT for III/IV HL. PATIENTS AND METHODS: All patients with stage III/IV HL referred to the Saint-Louis Hospital between January 2003 and May 2007 were studied. A Groupe d'Etudes des Lymphomes de l'Adulte/European Organisation for Research and Treatment of Cancer RCT, to compare ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with increased-dose BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), was open for recruitment. Noninclusion criteria and physician's reasons for non-recruitment were prospectively recorded. The reasons for patient's refusal were collected retrospectively. Logistic regression analyses were carried out in order to identify factors predicting inclusion. RESULTS: A total of 102 patients were diagnosed, among whom 51% were included. Seven patients were ineligible, 22 refused to participate, and 21 were not enrolled due to the physician's decision. Main reasons for patients' refusal were standard treatment preference and concerns about experimental arm toxicity, mainly infertility risk. Conditions that could hamper accurate follow-up and toxicity concerns accounted for most of the physicians' reasons. Adverse prognostic factors [B symptoms (odds ratio, OR = 5.35) and international prognostic score > or =3 (OR = 2.69)] were independently associated with inclusion. CONCLUSION: Despite an attractive protocol, only 51% of patients were included. It highlights concerns about selection of patients and the difficulty to obtain informed consent with better prognostic profile patients.

Slow Gait Speed Is an Independent Predictor of Early Death in Older Cancer Outpatients: Results from a Prospective Cohort Study.

OBJECTIVE: To assess the predictive value of gait speed for early death in older outpatients with cancer. DESIGN: Prospective bicentric observational cohort study. SETTING: The Physical Frailty in Elder Cancer patients (PF-EC) study (France). PARTICIPANTS: One hundred and ninety outpatients with cancer during the first 6 months of follow up in the PF-EC study. MEASUREMENTS: The association between usual gait speed over 4 m alone (GS) or included in the short physical performance battery (SPPB) and overall survival within 6 months following a comprehensive geriatric assessment (CGA). A Cox proportional-hazard regression model was performed in non-survivors for clinical factors from the CGA, along with c reactive protein (CRP). Two models were created to assess GS alone and from inclusion in the SPPB. RESULTS: The mean age was 80.6 years, and 50.5% of the participants were men. Death occurred in 11% (n=22) of the participants within the 6 month follow up period. Of these participants, 98% had solid cancers, and 33% had a metastatic disease. A GS < 0.8 m/s (HR=5.6, 95%CI=1.6-19.7, p=0.007), a SPPB < 9 (HR=5.8, 95%CI=1.6-20.9, p=0.007) and a CRP of 50 mg/l or greater (p<0.0001) were significantly associated with early death in the two multivariate analyses. Cancer site and extension were not significantly associated with early death. CONCLUSION: Walking tests are associated with early death within the 6 month follow up period after a CGA independent of cancer site and cancer extension. GS alone < 0.8 m/s is at least as efficacious as the SPPB in predicting this outcome. GS alone could be used routinely as a marker of early death to adapt oncologic therapeutics. Further studies are needed to validate these preliminary data.

Fludarabine plus cyclophosphamide in Waldenström's macroglobulinemia: results in 49 patients.

Fludarabine (FDR) therapy gives a response rate of about 30% in previously treated patients with Waldenström's macroglobulinemia (WM). The combination of FDR and cyclophosphamide (Cy) has been shown to be effective in chronic lymphoproliferative disorders. We administered the combination of FDR (30 mg/m2 i.v. D1-D3) and Cy (300 mg/m2 i.v. D1-D3) to 49 patients. Median age was 64 years. The median hemoglobin, albumin, beta 2 microglobulin and immunoglobulin M (IgM) levels were 9.9 g/100 ml, 39.6 g/l, 3 mg/l and 24.7 g/l, respectively. In all, 14 patients (29%) had not previously been treated. FDR/Cy was administered every 4 weeks for a median of four cycles. In all, 38 patients (77.6%) had partial responses, nine had stable disease and two had progressive disease. After a median of follow-up of 25 months, six patients relapsed and two patients developed large-cell lymphoma. The median time to treatment failure was 27 months. The main toxicity was hematological. In all, 12 patients died, four from progression, one from large-cell lymphoma, three from infection and four from a second malignancy. Two factors negatively influenced overall and event-free survival, age >65 years and IgM <40 g/l. The FDR/Cy combination, therefore, gives a high response rate in WM, even in previously treated patients with factors of poor prognosis.

Effect of immune modulation in relapsed peripheral T-cell lymphomas after post-allogeneic stem cell transplantation: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with non-immunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68-48.21), P=0.0009) and skin relapse (odds ratio: 4.15 (1.04-16.50), P=0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17-0.640), P=0.0009). This large series provides encouraging evidence of a true GvL effect in this disease.

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

PURPOSE: To assess the feasibility and efficacy of intensive chemotherapy with hematopoietic stem-cell rescue (IC + HCR) in patients with refractory or recurrent primary CNS lymphoma (PCNSL) or intraocular lymphoma (IOL). PATIENTS AND METHODS: IC consisted of thiotepa 250 mg/m(2)/d days -9 through -7, busulfan 10 mg/kg (total dose) days -6 through -4, and cyclophosphamide 60 mg/kg/d days -3 and -2. Intravenous clonazepam 2 mg/d was given prophylactically from the day before initiation of busulfan therapy to the day after completion of busulfan therapy. Patients with refractory or recurrent PCNSL underwent IC + HCR only if they were chemosensitive to two cycles of salvage treatment with cytarabine (2 g/m(2)/d days 2 through 5 and 50 mg/m(2)/d days 1 through 5 in a 12-hour infusion) and etoposide (VP-16; 200 mg/m(2)/d days 2 through 5) (CYVE). Patients with IOL refractory to high-dose methotrexate (MTX) and cytarabine entered the IC + HCR program directly. RESULTS: Twenty-two patients (10 with relapses, 12 with refractory disease) were enrolled. Twenty patients entered the IC + HCR program: twelve entered after CYVE treatment, seven entered directly, and one had previously been retreated with high-dose MTX. Before IC, eight patients were in complete remission (CR), four were in partial remission (PR), one had stable disease, and seven had refractory disease. After IC + HCR, 16 patients entered CR, two remained in PR, one had stable disease, and one had disease progression. Fourteen patients remained alive (median follow-up time, 41.5 months). The overall probability of survival at 3 years was 63.7%. After IC, that probability was 60% and the 3-year probability of event-free survival was 53%. Seven patients had neurologic adverse events during the entire procedure. CONCLUSION: IC + HCR proved feasible and effective in patients with refractory or recurrent PCNSL or IOL. The entire procedure seemed to be most toxic in patients > or = 60 years. A prospective multicenter study is ongoing.

Durable remission after aggressive chemotherapy for very late post-kidney transplant lymphoproliferation: A report of 16 cases observed in a single center.

PURPOSE: Posttransplant lymphoproliferative diseases (PTLDs) represent a group of potentially lethal lymphoid proliferations that may complicate the course of solid organ transplantation. Although early-onset PTLDs frequently have a favorable outcome, late-onset PTLDs behave more alike aggressive lymphoma. We report a monocentric retrospective study that focused on PTLDs occurring later than 1 year after kidney transplantation (very late-onset PTLDs) to define their incidence, clinical presentation, pathologic features, and outcome. We particularly emphasized the follow-up of patients treated with conventional chemotherapy. PATIENTS AND METHODS: The medical histories of all patients who developed very late-onset PTLD in our institution were reviewed, and diagnostic biopsy materials were retrospectively studied. RESULTS: Very late-onset PTLDs were diagnosed in 16 (1.1%) of 1,421 patients. Mean (+/- SD) time to tumor onset was 103.93 +/- 70.88 months. Most tumors were Epstein-Barr virus-related monomorphic large-cell PTLDs of B phenotype. Ten patients received conventional chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone regimen). Two of them died within 2 months, two achieved partial remission, and six achieved definitive complete remission. Overall median survival time was 13 months and rose to 27 months in the treated group. The main cause of mortality was sepsis. None of the treated patients experienced rejection despite withdrawal of immunosuppressive treatment. CONCLUSION: Despite characteristics of aggressive lymphoma, very late-onset PTLDs after renal transplantation may respond to conventional chemotherapy. However, because a high rate of infectious complications occurred, new therapeutic strategies, such as combinations of anti-CD20 monoclonal antibodies and lower doses of chemotherapy, are warranted.

Identification of prognostic factors in 61 patients with posttransplantation lymphoproliferative disorders.

PURPOSE: Prognostic studies of posttransplantation lymphoproliferative disorders (PTLDs) are hindered by the small number of cases at each transplant center. We analyzed prognostic factors and long-term outcome according to clinical manifestations, pathologic features, and treatment and investigated the prognostic value of the non-Hodgkin's lymphoma International Prognostic Index (IPI) in 61 patients with PTLD. PATIENTS AND METHODS: We studied 61 patients in two institutions who developed PTLD and analyzed factors influencing the complete remission and survival rates. RESULTS: In univariate analysis, factors predictive of failure to achieve complete remission were performance status (PS) > or = (P =.0001) and nondetection of Epstein-Barr virus (EBV) in the tumor (P =.01). Only a negative link with PS > or = 2 was observed in multivariate analysis. In univariate analysis, factors predictive of lower survival were PS > or = 2, the number of sites (one v > one), primary CNS localization, T-cell origin, monoclonality, nondetection of EBV, and treatment with chemotherapy. The IPI failed to identify a patient subgroup with better survival and was less predictive of the response rate than was a specific index using two risk factors (PS and number of involved sites), which defined three groups of patients: low-risk patients whose median survival time has not yet been reached, intermediate-risk patients with a median survival time of 34 months, and high-risk patients with a median survival time of 1 month. CONCLUSION: PS and the number of involved sites defined three risk groups in our population. The value of these prognostic factors needs to be confirmed in larger cohorts of patients treated in prospective multicenter studies.

The Xvex-1 antimorph reveals the temporal competence for organizer formation and an early role for ventral homeobox genes.

The organizer in vertebrate embryos has been shown to play a central role in their development by antagonizing ventralizing signals and promoting dorsal development. The ventral homeobox gene, Xvex-1, is capable of fulfilling some of the functions of BMP-4. By fusion to activation and repression domains, Xvex-1 was shown to function as a repressor of transcription. The activator version of Xvex-1, the antimorph, was made inducible by fusion to the ligand binding domain of the glucocorticoid receptor. The organizer genes, gsc and Otx-2, were identified as direct targets of Xvex-1. The XVEX-1 antimorph can induce the formation of secondary axes. Temporal analysis of secondary axis induction revealed that the competence to induce a secondary organizer ends with the onset of gastrulation. The same temporal competence window was exhibited by an inducible gsc construct. Partial loss of Xvex-1 activity was able to improve the efficiency of secondary axis induction by the dominant negative BMP receptor or Smad6. These observations together with the early widespread expression of Xvex-1 throughout the embryo prior to gastrulation encoding a homeodomain repressor protein, suggest that elements of the ventral signaling pathway play an important role during late blastula in restricting the formation of Spemann's organizer.

Treatment of chronic hepatitis C virus in allogeneic bone marrow transplant recipients.

We recently reported an increased incidence of cirrhosis in hepatitis C virus (HCV)-infected stem cell transplant (SCT) recipients. Here, we describe our experience in the treatment of these patients, which has been, to date, poorly reported in the literature. Among 99 HCV-infected HCT recipients, 36 had HCV-related liver lesions on biopsy requiring therapy. Owing to HCV treatment contraindications, only 61% of patients (22/36) could be treated. In all, 12 patients received more than one course of anti-HCV treatment if they had HCV RNA still detectable after the first course of treatment and no treatment contraindications. Combined therapy (pegylated interferon (IFN): n=9, or standard IFN: n=9, in combination with ribavirin) led to sustained virological response in 4/18 (20%) patients as compared to 2/20 (10%) in patients who received IFN alone. Hematological toxicity was more frequent with combined therapy. While anemia responded to erythropoietin and/or dose modification, thrombocytopenia usually led to treatment interruption (n=3). This study thus highlights the efficacy of combined therapy and emphasizes the fact that the undue safety concerns are not a problem when treating this particular population.