Scleromyxoedema treated with autologous stem cell transplantation.
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Combined Modality Therapy↗
Biomedical subjects
M Rovira
Publications and source records attributed to M Rovira.
Donor age and degree of HLA matching have a major impact on the outcome of unrelated donor haematopoietic cell transplantation for chronic myeloid leukaemia.
We analysed the outcome of 92 consecutive unrelated donor haematopoietic cell transplantations (UD-HCTs) performed in Spain to treat adult patients with CML in the first chronic phase (1CP). Patients' and donors' median age was 32 (15-49) and 36 (22-56) years, respectively. In all, 73 pairs (79%) matched for A, B+/-C and DRB1+/-DQB1 loci and 19 had > or =1 mismatch. Their probability of survival and disease-free survival at 4 years were 50 and 46%, respectively. Pretransplant factors associated with a better survival were patient age <25 years (P=0.035), donor age < or =36 years (P=0.012), use of cyclosporine since day -7 (P=0.001), and matching 8/8, 9/10 or 10/10 loci at allele level (P=0.003). In multivariate analysis only donor age (P=0.003; RR=3.1 (95% CI: 1.3-7.1)) and degree of HLA-matching (P=0.009; RR: 7.7 (95% CI: 1.8-33)) maintained their significance. The addition of these two variables to the EBMT prognostic score allowed an adequate risk assessment for patients receiving a UD-HCT during 1CP. Our analysis shows that in patients with a young and fully allele-matched donor, UD-HCT should be considered in the initial therapeutic algorithm due to its excellent outcome (92% survival at 2 years).
Adolescent↗
Prospective evaluation of procalcitonin in adults with non-neutropenic fever after allogeneic hematopoietic stem cell transplantation.
The aim of this study was to analyze whether procalcitonin (PCT) is a diagnostic marker of infectious diseases during the non-neutropenic period in patients who have received an allogeneic hematopoietic stem cell transplant (HSCT). We included 65 patients in whom an allogeneic HSCT was performed in a 2-year period (April 2002-July 2004). PCT levels were monitored in every febrile episode by an immunoluminometric assay. Febrile episodes were classified according to the final diagnosis in: fever of unknown origin, microbiologically or clinically documented infection and non-infectious fever. Fifty-two febrile episodes in the non-neutropenic period were included in the study. Out of these 52, 26 had an infectious etiology: 11 fulfilled criteria for probable or proven invasive aspergillosis (IA), three were classified as possible invasive fungal infection (IFI) and 12 episodes were caused by other infections. Mean values of PCT on the first day of admission were: 8.0 (+/- 4.9) in probable-proven IA (P = 0.013, Kruskall-Wallis), 4.5 (+/- 3.4) in possible IFI and 1.5 (+/- 0.9) in infections other than IFI. Therefore, we could conclude that during the non-neutropenic phases of allogeneic HSCT, a high PCT value is associated significantly with IA.
Adult↗
The use of a high-FeO olivine rock as a redox buffer in a nuclear waste repository.
Due to the higher stability of the spent nuclear fuel (mainly composed of UO2) under reducing conditions, and in order to enhance the retention/retardation of some key radionuclides, the olivine rock from the Lovasjärvi intrusion has been proposed as a potential redox-active backfill-additive in deep high-level nuclear waste (HLNW) repositories. In this work, two different approaches have been undertaken in order to establish the redox buffer capacity of olivine rock: (1) The capacity of the rock to respond to changes in pH or pe has been demonstrated and the final (pH, pe) coordinates agree with the control exerted by the system Fe(II)/Fe(III). (2) The rate of consumption of oxygen has been determined at different pH values. These rates are higher than the ones reported in the literature for other solids, what would point to the possibility of using this rock as an additive to the backfill material in a HLNW.
Buffers↗
Global and regional gray matter reductions in ADHD: a voxel-based morphometric study.
Attention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by inattentiveness, motor hyperactivity and impulsivity. According to neuroimaging data, the neural substrate underlying ADHD seems to involve fronto-striatal circuits and the cerebellum. However, there are important discrepancies between various studies, probably due to the use of different techniques. The aim of this study is to examine cerebral gray (GM) and white (WM) matter abnormalities in a group of ADHD children using a voxel-based morphometry protocol. The sample consisted of 25 children/adolescents with DSM-IV TR diagnosis of ADHD (medicated, aged 6-16 years) who were compared with 25 healthy volunteer children/adolescents. ADHD brains on an average showed a global volume decrease of 5.4% as compared to controls. Additionally, there were regionally specific effects in the left fronto-parietal areas (left motor, premotor and somatosensory cortex), left cingulate cortex (anterior/middle/posterior cingulate), parietal lobe (precuneus bilaterally), temporal cortices (right middle temporal gyrus, left parahippocampal gyrus), and the cerebellum (bilateral posterior). There were no differences in WM volume between ADHD children and control subjects. The results are consistent with previous studies that used different techniques, and may represent a possible neural basis for some of the motor and attentional deficits commonly found in ADHD.
Adolescent↗
Invasive pulmonary aspergillosis in solid organ and bone marrow transplant recipients.
BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a major cause of mortality in transplant recipients. New strategies in therapy are needed. METHODS: We prospectively followed all solid organ and bone marrow transplant recipients from January 1998 to January 2003 who showed pulmonary infiltrates. We retrospectively analyzed all of the patients diagnosed as having IPA. Clinical and epidemiological data were collected. Influence of new treatment strategies on survival was also analyzed. RESULTS: Thirty-one cases of API were found: 8 definite, 18 probable, 5 possible among recipients of liver (11), bone marrow (9), kidney (7), kidney-pancreas (3), and heart (1) transplants. Five patients (16%) were previously receiving antifungal prophylaxis. The most common symptoms were fever (74%) and dyspnea and dry cough (48%). Six cases (19%) showed dissemination to extrapulmonary sites: central nervous system (CNS) in five and bone in one. The most common radiographic patterns were alveolar infiltrates (58%); the lesions were usually diffuse and bilateral (58%). The most common Aspergillus species identified was A. fumigatus (74%). The test to detect Aspergillus antigen (galactomannan) in serum performed in 13 cases, was positive in eight (61%). The crude mortality rate was 61% (19 of 31), but in patients on mechanical ventilation, it was 94% (OR 88, IC 95%: 7.1-1094), and in patients with CNS involvement, it was 100%. The influence of the different treatment regimens on survival was analyzed in definite and probable cases: Group 1 (12) included patients who received conventional monotherapy and group 2 (12) patients received combination antifungal therapy or liposomal amphotericin B (1-AMB) at high doses. The mortality in group 1 was 83% (10 of 12), and in group 2 it was 42% (5 of 12) (P < 0.05). CONCLUSIONS: The mortality rate of IPA remains high, especially among patients with CNS involvement or those under mechanical ventilation. Combined antifungal therapy or monotherapy with 1-AMB at high doses significantly reduced mortality compared with conventional monotherapy.
Amphotericin B↗
Patient-rated emotional and physical functioning among hematologic cancer patients during hospitalization for stem-cell transplantation.
In this 3-year prospective inpatient study, 220 patients received stem-cell transplantation (SCT) for hematologic cancer at a single institution. The objective of the study is to provide data on patient-rated emotional (depression and anxiety) and physical (overall physical status, energy level, and systemic symptomatology) functioning during hospitalization for SCT and to compare whether these differ between autologous and allogeneic SCT. Patients were assessed at hospital admission (T1), day of SCT (T2), and 7 days (T3) and 14 days (T4) after SCT, yielding a total of 852 evaluations. For the overall sample, anxiety was highest at T1 and decreased afterwards; a marked worsening in physical health status variables corresponded with a sharp increase in depression from T1 to T3, and was followed by an improvement in physical health and a reduction of depression. Compared to allogeneic SCT, a better physical outcome for autologous SCT was demonstrated by the significant group effect for systemic symptomatology and by the significant group x time interaction for overall physical status and energy level; there were no significant differences in depression or anxiety between SCT groups. These findings have implications for treatment decision making, coping with the transplantation process, and improving prevention and treatment strategies.
Adolescent↗
Formation of studtite during the oxidative dissolution of UO2 by hydrogen peroxide: a SFM study.
Understanding the formation of alteration phases on the surface of spent nuclear fuel, such as those observed during leaching experiments, is necessary in order to predict the concentration of radionuclides in the near-field of a final repository. Hydrogen peroxide has been identified as one of the oxidants formed by the radiolysis of water in the presence of spent nuclear fuel; especially due to alpha activity. The presence of this species in solution can contribute to the formation of uranium peroxide secondary phases. In this work, we have studied the oxidative dissolution of synthetic UO2 disks in hydrogen peroxide solutions of two different concentrations (5 x 10(-4) and 5 x 10(-6) mol dm(-3)), both at pH 5.8 +/- 0.1. The solid surface evolution of the disks has been followed by means of ex-situ scanning force microscope (SFM) measurements, and uranium concentration in solution has been determined by inductively coupled plasma mass spectrometry. During the first stage of the experiment, SFM images indicate that only UO2 dissolution is occurring. After 142 h, a secondary phase is observed on the surface of the solid at 5 x 10(-4) mol dm(-3) hydrogen peroxide concentration. This secondary phase has been identified by X-ray diffraction as studtite (UO4 x 4H2O). From the analysis of SFM topographic profiles at different elapsed times, a precipitation rate for the studtite has been estimated to be in the range of (8-32) x 10(-10) mol m(-2) s(-1).
Forecasting↗
Mycobacterial infection: a difficult and late diagnosis in stem cell transplant recipients.
The Infectious Diseases Working Party of the European Blood and Marrow Transplant Group conducted a survey to obtain information about the frequency, presentation, and treatment of mycobacterial infection (MBI) in stem cell transplant (SCT) recipients. Among 29 centers, MBI was diagnosed in 0.79% of 1513 allogeneic and 0.23% of 3012 autologous SCT recipients during 1994-1998 a median of 160 days after transplantation. The mean interval between first symptoms and diagnosis was 29 days and was still longer for patients with atypical MBI or recipients of corticosteroid therapy. The prevalence of MBI was highest among those who received matched unrelated or mismatched STCs from related donors. Of 31 patients, 20 had tuberculosis, 8 had atypical MBI, and 3 had diagnoses based on histological findings only. Five patients (16%) died, all of whom had received an allogeneic SCT. Because of the increased numbers of unmatched donors and transplantation programs in countries with a high prevalence of tuberculosis, constant vigilance is required to early detect MBI in SCT recipients.
Adolescent↗
Clinical and MRI outcome after autologous hematopoietic stem cell transplantation in MS.
The authors report the outcome of 14 patients with severe multiple sclerosis treated with autologous hematopoietic stem cell transplantation (AHSCT) after a median follow-up period of 3 years. The 3-year actuarial probability of progression-free survival was 85.7% and that of disease activity-free survival was 46.4%. On MRI, no T1-enhanced lesions were detected after AHSCT. The mean change in T2 lesion volume from baseline to the third year was -20.2% and that of the corpus callosum area was -12.7%; 50% of this reduction was seen during the first year.
Actuarial Analysis↗
High-dose therapy/autologous stem cell transplantation in patients with chemosensitive multiple myeloma: predictors of complete remission.
High-dose therapy (HDT) followed by autologous stem cell support is widely used as intensification treatment in patients with multiple myeloma (MM) responsive to the initial chemotherapy. However, there is growing evidence that only the subset of patients who achieve complete remission (CR) actually benefit from this approach. The aim of this study was to identify pretransplant predictors of CR in responding myeloma patients intensified with HDT. A total of 59 patients with chemosensitive disease received myeloablative therapy. The intensification regimen consisted of MEL-200 (23), MEL-140/TBI 12 Gy (21) or busulfan-based regimens (15). Serum and urine negative immunofixation were required for CR. After HDT, the CR rate increased from 8 to 37%. For the overall series, the median event-free survival (EFS) and overall survival (OS) from the initiation of therapy were 41 and 68 months, respectively. Patients who achieved CR had an EFS (median 47 vs 36 months; P=0.023) as well as an OS (median not reached vs 60 months; P=0.006) significantly longer than those attaining a lower degree of response. Finally, the pretransplant features significantly associated to CR were a low M-protein size (serum </=10 g/l and urine <0.5 g/24 h) (P=0.0003) and a proportion of bone marrow plasma cells of </=5% (P=0.02).
Adult↗
Outbreaks of infectious diseases in stem cell transplant units: a silent cause of death for patients and transplant programmes.
Following the closure of the National Blood and Bone Marrow Transplant Unit in Dublin, because of an outbreak of vancomycin-resistant enterococcal infection, a survey was carried out by the EBMT to investigate the occurrence of outbreaks of infection in SCT units and the impact on patient morbidity, mortality and the administration of the transplant programme over a 10-year period from 1991 to 2001. A total of 13 centres reported 23 outbreaks of infection involving 231 patients: 10 bacterial, eight viral and five fungal outbreaks were reported and 56 deaths were attributed to infection. All fungal and bacterial deaths and the majority of viral deaths occurred in allograft recipients. In all outbreaks, the infection was reported to be hospital acquired and in all the viral, and half the bacterial infections, cross-infection was a major factor. All viral, four of 10 bacterial and three of five fungal outbreaks occurred in HEPA filtered rooms. A total of 12 SCT units reported a partial or total closure. The introduction of mandatory quality management systems such as JACIE should result in a change in attitude to 'incident reporting' and together with future surveys should reduce the incidence of infectious outbreaks in SCT units.
Aspergillosis↗
Measurement of C-reactive protein in adults with febrile neutropenia after hematopoietic cell transplantation.
The aim of this study was to evaluate the usefulness of C-reactive protein (CRP) monitoring in the differential diagnosis and prognosis of febrile neutropenic episodes in hematopoietic cell transplantation (HCT). In all, 100 patients were enrolled in the study. The CRP was determined in serum every 48 h from admission until resolution of the febrile episode. All patients presented with fever during the post-HCT neutropenic period. The febrile episodes were classified as microbiologically documented infection in 32 cases, clinically documented infection in 27 patients and fever of unknown origin in 41 patients. The mean CRP values on the first day of fever in these three groups were similar (NS). On the fifth day of antibiotic treatment, 50 patients remained pyrexial. Of these, 41 improved with modifications of antibiotherapy (mean CRP: 9.5 mg/dl; standard deviation (s.d.): 6.2) and nine died, five due to an infectious etiology (CRP: 21 mg/dl; s.d.: 4.4; P<0.003) and four from other causes (CRP: 11 mg/dl; s.d.: 3.4). On multivariate analysis, the CRP on the fifth day of treatment was an independent prognostic factor for fatal outcome. We conclude that persistent elevation of the CRP is an independent factor predicting a fatal outcome in patients who remain febrile on the fifth day of antibiotherapy during neutropenic febrile episodes post-HCT.
Adult↗
Safety of the concomitant use of caspofungin and cyclosporin A in patients with invasive fungal infections.
Caspofungin, an echinocandin antifungal agent, is active against invasive Aspergillus and Candida infections. In a phase I study in healthy volunteers, mild transient increases in serum aminotransferases were observed with the concomitant administration of caspofungin and cyclosporin A (CsA). As a result, it is recommended that the concomitant use of the two drugs be limited to those settings with appropriate risk-benefit balance. We retrospectively assessed safety data in 14 patients with refractory invasive mycoses who were treated concomitantly with CsA and caspofungin before the drug was licensed in Spain. In all, 13 patients were adults (median age, 31.5 years; range, 14-67 years). The average duration of concomitant therapy was 15 days (range, 2-43 days). No clinically significant elevations of serum aminotransferases were observed, and no patient had concomitant therapy discontinued or interrupted due to a drug-related adverse event. In this study of a limited number of patients, the coadministration of caspofungin and CsA was generally well tolerated.
Adolescent↗
Inflammatory response associated with pulmonary complications in non-HIV immunocompromised patients.
BACKGROUND: A study was undertaken to evaluate the local and systemic inflammatory response associated with pulmonary complications in immunocompromised patients and potential implications regarding severity and prognosis. METHODS: Levels of different inflammatory mediators were measured in the bronchoalveolar lavage (BAL) fluid and serum on days 1 and 4 after the identification of the pulmonary complication in 127 patients with different immunosuppressive conditions. RESULTS: Pulmonary complications were characterised by a high percentage of neutrophils and increased levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8 and IL-10 in the BAL fluid and high serum levels of TNF-alpha, IL-6, and plasma C-reactive protein (CRP). The inflammatory response was similar in the different groups of immunocompromised patients evaluated. The levels of proinflammatory cytokines were higher in patients with pulmonary infections, particularly those of bacterial aetiology. Patients with a more severe pulmonary infection had a more intense local and systemic inflammatory response. A BAL fluid IL-6 level of >40 pg/ml was an independent predictor of mortality (OR 4.65, 95% CI 1.3 to 16.1), together with a need for mechanical ventilation (OR 13.5, 95% CI 3.2 to 57.3). Patients who died had persistently high levels of CRP on day 4. CONCLUSIONS: The evaluation of the inflammatory response, particularly the determination of IL-6 levels in the BAL fluid and CRP in the serum, may be useful for deciding the appropriate management of pulmonary complications in immunocompromised patients.
Adult↗
[Prevention of fungal infections of endogenic origin].
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Antifungal Agents↗
Clinical applicability of the new EORTC/MSG classification for invasive pulmonary aspergillosis in patients with hematological malignancies and autopsy-confirmed invasive aspergillosis.
Diagnosis of invasive pulmonary aspergillosis (IPA) is often difficult. Recently, the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) has proposed new criteria for the classification of invasive fungal infections. We have studied the clinical applicability of this classification in 22 patients with hematological malignancies who had IPA at autopsy. While alive, according to the EORTC/MSG criteria, only 2 patients were classified as having proven IPA, 6 as probable, 13 as possible, and 1 was unclassifiable. Of the patients, 64% had no microbiological or major clinical criteria before death. Although the EORTC/MSG criteria are an important step forward in the standardization of definitions used for IPA in clinical research studies, most patients who die with extensive lung disease only reach a level of possible or probable IPA during life, further highlighting that these guidelines should not be used for clinical decision-making.
Adult↗
Phase I/II trials of autologous peripheral blood stem cell transplantation in autoimmune diseases resistant to conventional therapy: preliminary results from the Spanish experience.
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Adult↗