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ABSTRACT: The aim of this study was to analyse the incidence and risk factors for cytomegalovirus infection (CMV-I) and disease (CMV-D) after a reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (alloHSCT-RIC). We included 186 consecutive alloHSCT-RIC adult patients at risk for CMV reactivation (patient and/or donor CMV seropositivity). Conditioning regimen was based on fludarabine plus an alkylating agent. For guiding pre-emptive anti-CMV therapy, Pp65 Antigenemia (pp65Ag) (n=116) or quantitative polymerase chain reaction (quantPCR) (n=70) were used. The 2-year incidence of CMV-I and/or CMV-D was 36% (11% for CMV-D). Of note, 12/14 (86%) episodes of CMV-D in the pp65Ag group had lung involvement compared with only 3/15 (20%) in the quantPCR group (P=0.01). Importantly, the number of patients who developed CMV pneumonia with prior negative screening tests was unusually high (67% overall). Multivariate analysis of risk factors for CMV-D identified two risk factors: (i) steroid therapy for moderate-to-severe graft-vs-host disease (GVHD) (hazard ratio 4.7, P=0.02); and (ii) alternative donors (non-HLA-identical siblings) [hazard ratio 2.7, P=0.002]. Our findings suggest that CMV is still a major concern in alloHSCT-RIC. Variables associated with poor anti-CMV T-cell recovery (that is, GVHD and donor type) are helpful in identifying patients at higher risk for CMV-D in the alloHSCT-RIC setting.
Bone marrow transplantation 09/2009; 45(3):534-42. · 3.00 Impact Factor
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R Martino,
J L Piñana,
R Parody,
D Valcarcel,
A Sureda,
S Brunet,
J Briones,
J Delgado,
F Sánchez, N Rabella,
J Sierra
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ABSTRACT: We have analyzed the incidence and risk factors for the occurrence of invasive aspergillosis (IA) among 219 consecutive recipients of an allogeneic hematopoietic SCT after a reduced-intensity conditioning regimen (Allo-RIC). Twenty-seven patients developed an IA at a median of 218 days (range 24-2051) post-Allo-RIC, for a 4-year incidence of 13% (95% confidence interval 4-24%). In multivariate analysis, risk factors for developing IA were steroid therapy for moderate-to-severe graft vs host disease (GVHD) (Hazard Ratio (HR) 2.9, P=0.03), occurrence of a lower respiratory tract infection (LRTI) by a respiratory virus (RV) (HR 4.3, P<0.01) and CMV disease (HR 2.8, P=0.03). Variables that decreased survival after Allo-RIC were advanced disease phase (HR 1.9, P=0.02), steroid therapy for moderate-to-severe GVHD (HR 2.2, P<0.01), not developing chronic GVHD (HR 4.3, P<0.01), occurrence of LRTI by an RV (HR 3.4, P<0.01) and CMV disease (HR 2, P=0.01), whereas occurrence of IA had no effect on survival (P=0.5). Our results show that IA is a common infectious complication after an Allo-RIC, which occurs late post-transplant and may not have a strong effect on survival. An important observation is the possible role of LRTI by conventional RVs as risk factors for IA.
Bone marrow transplantation 04/2009; 44(11):749-56. · 3.00 Impact Factor
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L Guirado, N Rabella,
J M Díaz,
C Facundo,
A Maderuelo,
N Margall,
I Silva,
R García-Maset,
J Calabia,
I Giménez,
N Garra,
R Solà,
J A Ballarín
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ABSTRACT: Prophylactic and pre-emptive therapy with oral valganciclovir for cytomegalovirus infection in renal transplant recipients. Background: Cytomegalovirus infection is a very important health problem in solid organ transplant recipients (SOT). Once-daily valganciclovir has been shown to be as clinically effective and well tolerated as oral ganciclovir tid in the prevention of CMV infection in high risk SOT recipients.
The aim of the present study was to evaluate the incidence and severity of CMV disease in 150 renal transplant recipients that received either prophylactic [high risk group (HR), N = 66] or pre-emptive [low risk group (LR), N = 84] therapy with oral valganciclovir (900 mg/day vo) for three months according to their basal risk. Patients were monitored for signs and symptoms of CMV disease and CMV plasma viral load was assessed weekly.
A total of 31 patients (47%) of the HR and 26 patients (31%) of the LR presented a positive CMV PCR result. Twelve patients (14.3%) in the LR that had a high viral load (CMV PCR > 1,000 copies/mL) but remained asymptomatic received pre-emptive therapy. Four patients (4.7%) in the LR, after an average time of 35 days after transplant and two patients (4.5%) in the HR, after prophylactic treatment was completed, developed CMV disease. The disease was mild-moderate in most of the cases. Those patients that developed CMV disease responded to treatment with iv ganciclovir for 14 days followed by treatment with oral valganciclovir for up to three months.
Prophylactic treatment with oral valganciclovir for CMV prevention is only required in high risk solid organ transplant recipients.
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 01/2008; 28(3):293-300. · 1.00 Impact Factor
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ABSTRACT: The impact of human enterovirus (HEV) and human rhinovirus (HRV) respiratory tract infections in adult patients with hematological malignancies has been infrequently reported. We retrospectively studied 31 patients with an upper or lower respiratory tract infection (URTI/LRTI) by HEV (n = 18) or HRV (n = 15). At onset, a LRTI was present in 6 (33%) and 2 (13%) episodes of HEV and HRV infections, respectively, with or without an URTI. Progression to LRTI (pneumonia) from prior URTI was seen in 1 (6%) and 2 (13%) HEV and HRV infections, respectively. The presence of lymphocytopenia (<0.5 x 10(9)/l) was higher in LRTI by HEV: 4/5 (80%) versus 2/10 (20%) by HRV. Eight of 18 (44%) patients with immunosuppression versus 3/14 (21%) patients with no immunosuppression at the onset of respiratory infection developed a LRTI. Thirteen per cent of patients had associated respiratory infections from bacteria, aspergillus, or CMV. Pulmonary aspergillosis was diagnosed in 20% of HRV infections. Three of 11 patients (27%) with a LRTI died, but pulmonary copathogens were also involved in all cases. In conclusion, HEV and HRV can be associated with LRTI in immunocompromised patients, although their direct impact on mortality is uncertain.
American Journal of Hematology 09/2007; 82(9):807-11. · 4.67 Impact Factor
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ABSTRACT: We compared the efficiency of detection using pp65 antigenemia, reverse transcription-polymerase chain reaction (RT-PCR), and viruria for the diagnosis of cytomegalovirus (CMV) infections after kidney transplantation.
We evaluated 40 renal transplant recipients between weeks 5 and 12 after transplantation, including 179 blood and 181 urine specimens.
All positive samples by antigenemia were also positive by PCR. However, in 52 cases only PCR was positive (kappa = 0.134 [P < .001]). Viruria was positive in 66 cases, but only 26 were CMV PCR positive. In 34 cases, viruria was negative and PCR positive (P = .192).
Detection of DNA in serum is a more sensitive method than antigenemia for the diagnosis of CMV infection. Viruria was not related to the presence of CMV in blood.
Transplantation Proceedings 11/2005; 37(9):3768-9. · 1.00 Impact Factor
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ABSTRACT: Infection by the influenza virus may pass undetected in many adult patients attended to in the emergency department because its diagnosis usually relies on clinical manifestations, which can be distorted by symptoms of a preexisting disease, superposed complications or nontypical manifestations of influenza virus infection (confusing symptoms).
We performed this observational, prospective study with an antigen detection test by indirect immunofluorescence assay (IFA) to estimate the presence of influenza virus infection in such patients. No confirmatory test was performed to validate a positive or negative IFA result. Then we compared those who were antigen positive to those who were negative and also analyzed those who were positive classified by age, comorbidity and clinical presentation. We also evaluated the use of medical and hospital resources and vaccination status. Posterior pharynx swab specimens from 136 consecutive adult patients, 74 women and 62 men with a mean age of 68.7 +/- 17.9 (range: 18-97) years attended to in the emergency department of a university hospital in Barcelona during the 1999-2000 influenza epidemic were examined. Tested patients presented either a classical influenza syndrome, a deterioration of a previous condition or any abrupt onset of symptoms without an obvious cause.
Influenza A virus antigen was detected in 99 (72.8%) of the 136 patients included in the study. Confusing symptoms were present in 86 patients with laboratory-confirmed influenza and 40 of them lacked influenza syndrome. Prostration, aching and fever out of proportion to catarrhal symptoms (disproportionate prostration) and cough were independent predictors for this diagnosis (OR = 5.14; 95% CI: 1.98-13.35, p = 0.001 and OR = 4.40, 95% CI, 1.65-11.75, p = 0.03, respectively). Among the 99 patients who tested positive, 72 were >or= 65 years of age. This older positive group compared to the 27 also positive < 65 (non-old) had a tendency to show symptoms mediated by cytokines less frequently: malaise was present in 76.4% of the older positive patients vs 92.6% in the non-old positive ones, p = 0.07. The equivalent percentages for muscle ache were: 56.9% vs 77.8%, p = 0.06; for dysthermia: 54.2% vs 70.4%, p = 0.08; for headache: 35.2% vs 66.7%, p = 0.005, and for disproportionate prostration: 47.2% vs 66.7%, p = 0.08. Cough was more frequent in the older positive group: 94.4% vs 77.8%, p = 0.02. Older positive patients were also hospitalized and received antibiotics more frequently than the non-old positive ones: 65.3% vs 40.7%, p = 0.03 and 81.9% vs 63.0%, p = 0.046, respectively. Hospitalization was independently correlated with the presence of complications (OR = 4.5, 95% IC 1.27-15.95, p = 0.02). Patients with the highest comorbidity, evaluated with the Charlson scale, were more inadequately vaccinated than those with moderate or low comorbidity.
Influenza virus infection has a great and underestimated impact in the emergency department during influenza epidemics. High frequency of confusing symptoms, which overcome classical influenza syndrome in adult people with comorbidity, may explain this effect. Disproportionate prostration and cough are symptoms that independently predict its diagnosis in the global adult population, whereas in the elderly, fever and cough should arouse this suspicion whether or not they present classic symptoms. In our setting, individuals with high comorbidity are inadequately vaccinated.
Infection 04/2004; 32(2):89-97. · 2.66 Impact Factor
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ABSTRACT: The in vitro susceptibility to acyclovir of 204 herpes simplex virus isolates from 165 immunocompromised patients treated at our hospital was determined by the cytopathic effect reduction assay. Approximately 95% of herpes simplex virus 1 and 73% of herpes simplex virus 2 isolates were inhibited by acyclovir at concentrations of <2 microgram/mL. From 8 patients (5%), an isolate with low susceptibility to acyclovir (50% inhibitory dose, >3 microgram/mL) was recovered. Medical records of 83 patients were reviewed. Lesions resolved in most of the patients, independent of treatment. Treatment failures were not always associated with isolation of an in vitro-resistant virus. On the contrary, when a virus with low susceptibility to acyclovir was isolated, resolution of the lesion was the rule. In 9 of 10 patients with subsequent recurrent episodes of disease, the susceptibility of the viruses isolated was similar to that of the first episode. Routine susceptibility testing in our geographic area is not encouraged because of the low incidence of acyclovir-resistant herpes simplex viruses.
Clinical Infectious Diseases 05/2002; 34(8):1055-60. · 9.15 Impact Factor
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Transplantation Proceedings 03/2002; 34(1):67-8. · 1.00 Impact Factor
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ABSTRACT: In vitro susceptibility to acyclovir of 96 strains of herpes simplex virus isolated from 80 immunocompromised patients attended in our hospital was studied by the cytopathic effect reduction assay. Ninety-eight percent (61/62) of herpes simplex virus 1 strains and 91% (31/34) of herpes simplex virus 2 strains were inhibited by acyclovir concentrations lower than 3 mg/l. In 5% of the patients herpes simplex strains resistant to acyclovir (ID(50) >3 mg/l) were isolated. Ninety-eight percent of the lesions caused by herpes simplex viruses susceptible to acyclovir (ID(50) <3 mg/l) resolved independently of treatment. In two cases, the cytopathic effect reduction assay was not able to predict treatment failure and persistance of the lesions was not always associated with isolation of a resistant strain in vitro. In four cases, isolation of a strain resistant to acyclovir was not indicative of treatment failure. In conclusion, we believe there is no need to routinely test susceptibility of herpes simplex viruses to acyclovir and that susceptibility testing should be indicated only in patients in whom lesions persist and other causes have been ruled out.
Revista espanola de quimioterapia: publicacion oficial de la Sociedad Espanola de Quimioterapia 12/2001; 14(4):351-7. · 0.81 Impact Factor
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ABSTRACT: Ganciclovir is the drug of choice for the treatment of acute cytomegalovirus infections. This antiviral agent is a nucleoside analog of guanine whose activity is dependent upon its intracellular phosphorylation to the triphosphate derivative. Foscarnet is used to treat immunosuppressed patients such as organ transplant recipients and AIDS patients with cytomegalovirus who do not tolerate or develop resistance to ganciclovir. Foscarnet is a pyrophosphate analog that directly inhibits viral DNA polymerase. Resistant isolates have been recovered from immunocompromised patients treated with both anticytomegalovirus compounds. The aims of this study were to prepare a plaque reduction assay to study the in vitro susceptibility of cytomegalovirus to ganciclovir and foscarnet, and to apply it to the knowledge of in vitro susceptibility values of cytomegalovirus isolated from clinical samples. Eighty isolates from patients who had never been treated with ganciclovir or foscarnet were tested for antiviral susceptibility. The plaque reduction assay took 6-8 weeks. The results are expressed as ID(50) (inhibitory dose 50), and the ID(50) values of ganciclovir were between 2.14 and 13.49 microM. The ID(50) for ganciclovir was higher that 12 microM in only two cases (2%). The molecular study of the DNA of these did not show any mutation in the UL97 gene. The ID(50) values of foscarnet were between 46.65 and 460.22 microM. In 78 cases (98%) foscarnet ID(50) was lower than 400 microM. These results were comparable with those obtained by other authors. To summarize, the frequency of cytomegalovirus strains resistant in vitro to ganciclovir and foscarnet in previously untreated patients was low and when it was present it did not involve therapeutic failure since the patients progressed favorably.
Revista espanola de quimioterapia: publicacion oficial de la Sociedad Espanola de Quimioterapia 07/2001; 14(2):155-64. · 0.81 Impact Factor
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European Journal of Clinical Microbiology 05/2001; 20(4):287-8. · 2.86 Impact Factor
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ABSTRACT: HIV-1 seropositive patients often exhibit thrombocytopenia, considered of multifactorial aetiology. Thrombopoietin (TPO), a recently isolated cytokine, is the main regulator of megakaryocyte and platelet production. The objective of this study was to analyse serum TPO levels in thrombocytopenic and non-thrombocytopenic HIV-1 infected patients. Serum TPO levels were measured by ELISA in 43 healthy individuals and in 88 HIV-1 infected patients: 68 thrombocytopenics and 20 non-thrombocytopenics. Thrombocytopenic HIV-1 infected patients showed higher TPO concentrations (263 +/- 342 pg/ml) than non-thrombocytopenics (191 +/- 86 pg/ml); levels in both groups were significantly higher than those of healthy controls (121 +/- 58 pg/ml). Two subgroups of thrombocytopenic patients, the autoimmune thrombocytopenic purpura (AITP) group and the mild thrombocytopenic group, presented TPO levels similar to those of non-thrombocytopenics. Patients exhibiting pancytopenia showed the highest TPO concentrations. However, there was no correlation between TPO levels and platelet counts in any group of HIV-1 infected patients. TPO levels in HIV-1 seropositive patients were slightly increased and the differences in TPO levels between thrombocytopenic and non-thrombocytopenic patients were generally small. The finding of mildly increased TPO levels along with the recently described recovery of thrombocytopenia following recombinant TPO administration confirms the implication of ineffective platelet production in the origin of HIV-associated thrombocytopenia.
European Journal Of Haematology 11/1999; 63(4):245-50. · 2.61 Impact Factor
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Archives of Internal Medicine 11/1999; 159(19):2367-8. · 11.46 Impact Factor
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ABSTRACT: The main difficulty of PCR-based clonality studies for B-cell lymphoproliferative disorders (B-LPD) is discrimination between monoclonal and polyclonal PCR products, especially when there is a high background of polyclonal B cells in the tumor sample. Actually, PCR-based methods for clonality assessment require additional analysis of the PCR products in order to discern between monoclonal and polyclonal samples. Heteroduplex analysis represents an attractive approach since it is easy to perform and avoids the use of radioactive substrates or expensive equipment.
We studied the sensitivity and specificity of heteroduplex PCR analysis for monoclonal detection in samples from 90 B-cell non Hodgkin's lymphoma (B-NHL) patients and in 28 individuals without neoplastic B-cell disorders (negative controls). Furthermore, in 42 B-NHL and in the same 28 negative controls, we compared heteroduplex analysis vs the classical PCR technique. We also compared ethidium bromide (EtBr) vs. silver nitrate (AgNO(3)) staining as well as agarose vs. polyacrylamide gel electrophoresis (PAGE).
Using two pair consensus primers sited at VH (FR3 and FR2) and at JH, 91% of B-NHL samples displayed monoclonal products after heteroduplex PCR analysis using PAGE and AgNO(3) staining. Moreover, no polyclonal sample showed a monoclonal PCR product. By contrast, false positive results were obtained when using agarose (5/28) and PAGE without heteroduplex analysis: 2/28 and 8/28 with EtBr and AgNO(3) staining, respectively. In addition, false negative results only appeared with EtBr staining: 13/42 in agarose, 4/42 in PAGE without heteroduplex analysis and 7/42 in PAGE after heteroduplex analysis.
We conclude that AgNO(3) stained PAGE after heteroduplex analysis is the most suitable strategy for detecting monoclonal rearrangements in B-NHL samples because it does not produce false-positive results and the risk of false-negative results is very low.
Haematologica 10/1999; 84(9):820-3. · 6.42 Impact Factor
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ABSTRACT: Lower respiratory tract infection is the most common complication in the immunocompromised patient. From January 1991 to December 1995, 785 consecutive patients with suspected respiratory tract infections were studied. One hundred ninety-nine viruses were isolated from 182 (23%) of 785 bronchoalveolar lavage fluid specimens. Cytomegalovirus was isolated from 131 patients, herpes simplex virus was recovered from 31, and conventional respiratory viruses (CRVs) were recovered from 36. There were 9 influenza A viruses, 2 influenza B viruses, 7 parainfluenza viruses, 5 respiratory syncytial viruses, 5 adenoviruses, 6 enteroviruses, and 3 rhinoviruses. We identified 22 patients from whom a CRV was the only microorganism recovered; 13 patients developed pneumonia, 10 had acute respiratory failure, 5 required support with mechanical ventilation, and 5 (23%) died. In conclusion, CRVs are frequent causes of respiratory illnesses and are associated with high rates of morbidity and mortality among immunocompromised patients.
Clinical Infectious Diseases 06/1999; 28(5):1043-8. · 9.15 Impact Factor
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ABSTRACT: In recent years, it has been recognised that the community respiratory viruses are a frequent cause of upper and lower respiratory tract infections in immunocompromised hosts such as bone marrow transplant recipients. By contrast, infections by non-polio enteroviruses have rarely been reported after stem cell transplantation. We present four cases of acute respiratory illness with enterovirus isolated as the sole pathogen from bronchoalveolar lavage. All four patients developed pneumonia and three died of progressive pneumonia, which reflects the severity of this complication. We conclude that enteroviral pulmonary infections may be a cause of severe pneumonia in immunocompromised hosts.
Bone Marrow Transplantation 04/1999; 23(5):511-3. · 3.75 Impact Factor
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ABSTRACT: We report three patients who developed a generalized rash with oral, genital or perianal ulcerations as a result of acute infection due to HIV. The primary infection was diagnosed by seroconversion (by means of EIA and Western blot techniques). Definitive diagnosis was established on days 52, 85 and 97 after the appearance of the rash. The p24 protein of the HIV was only detected in the early phase of the disorder in the two cases in which this study was carried out.
Anales de medicina interna (Madrid, Spain: 1984) 01/1999; 15(12):650-3.
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ABSTRACT: The optimal prophylactic strategy for cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation has not yet been established. The aim of this study was to analyze our single-center experience with a uniform protocol of CMV antigenemia-guided pre-emptive treatment with ganciclovir (GCV) after allografting. Fifty-two consecutive adult patients, 48 of them transplanted from HLA-identical matched related donors were included. T cell-depleted marrow or peripheral blood were used in 21 cases. After engraftment, weekly blood samples were tested for CMV pp65 antigenemia and viremia (conventional cultures) until day +100. GCV was started if CMV antigenemia and/or CMV viremia were detected. CMV infection (CMV-I) was found in 19 patients (37%). Seven patients suffered from CMV disease (CMV-D), three colitis and four pneumonias. There was one death directly related to CMV-D and three further cases died from refractory GVHD with CMV-D. Only one patient developed CMV pneumonia without any previous positive antigenemia and/or viremia. Multivariate analysis identified grades II-IV acute GVHD (P = 0.02) and peripheral blood stem cell transplantation (P = 0.03) to be risk factors for developing CMV-I. In conclusion, this monitoring protocol allowed early treatment of CMV-I without progression to CMV-D. Pre-emptive therapy had the additional advantage of avoiding GCV administration in most of our allograft recipients.
Bone Marrow Transplantation 12/1998; 22(9):899-904. · 3.75 Impact Factor
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ABSTRACT: Varicella zoster virus (VZV) infections are an important cause of morbidity after stem cell transplantation (SCT), with no differences in their overall incidence between allogeneic and autologous transplants. We report four patients who developed a disseminated VZV infection with visceral involvement after an allogeneic (n = 3) or autologous (n = 1) SCT. In all 4 cases, the initial symptom was severe abdominal pain which preceded the appearance of the classical herpetic vesicular skin lesions from two to four days in three cases, while one never developed skin lesions. The interval from the transplant to the infection ranged from 5 to 13 months, and all three allogeneic SCT received a T-cell depleted graft, although two suffered from chronic GVHD. All patients had clinical, radiologic and/or biochemical findings indicative of gastrointestinal or visceral involvement. An extensive bibliography review of this specific form of presentation of disseminated VZV infection is presented. The interval from the abdominal pain to the development of the skin lesions has ranged from one to 10 days, and this has led to a delay in the initiation of specific antiviral therapy in many cases, including our only fatal case. We conclude that an abdominal pain of unknown origin in this particular clinical setting should always be regarded as a possible prodromal phase of a disseminated VZV infection.
Medicina Clínica 07/1998; 111(1):19-22. · 1.38 Impact Factor
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Archives of Internal Medicine 03/1998; 158(6):680-1. · 11.46 Impact Factor
