Nuria Rabella

A Prospective Study Comparing Human Metapneumovirus with Other Respiratory Viruses in Adults with Hematologic Malignancies and Respiratory Tract Infections

Human metapneumovirus (hMPV) is a recently described paramyxovirus associated with upper and lower respiratory-tract infection (URI and LRI, respectively). We conducted a prospective study of URI and LRI in adults with hematologic malignancies during a 4-year period. We retrospectively tested samples by reverse-transcription polymerase chain reaction for hMPV and analyzed clinical data. Twenty-two (9%) of 251 episodes of respiratory infection tested positive for hMPV. Sixteen (73%) of the illnesses occurred in hematopoietic stem-cell transplant recipients. Nine patients with hMPV developed LRI; 3 of these patients died. hMPV is a common cause of respiratory infections in adults with hematologic malignancies, with associated morbidity and mortality.

Respiratory Virus Infections in Adults with Hematologic Malignancies: A Prospective Study

Abstract During a 2-year period, 157 consecutive episodes of respiratory virus infections that occurred in 130 patients with upper or lower respiratory tract infection were analyzed for respiratory viruses. A respiratory virus was identified in 75 episodes (48%), and several viruses were found in 13 episodes: there were a total of 56 influenza A virus infections, 14 respiratory syncytial virus infections, 8 adenovirus infections, 8 infections with parainfluenza virus types 1 or 3, and 7 enterovirus infections. On multivariate analysis, the only variable that predicted progression to pneumonia in patients with an upper respiratory tract infection was the presence of respiratory syncytial virus, whereas lymphocytopenia had a nonsignificant trend. Also, among the 38 patients who had pneumonia at any time during the episode, both respiratory syncytial virus and lymphocytopenia were commonly found. For both epidemiological and therapeutic considerations, frequent screening for respiratory viruses should be incorporated into the routine diagnostic study of patients with hematologic malignancies.

Conventional respiratory viruses recovered from immunocompromised patients: clinical considerations.

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.

Cytomegalovirus pp65 antigenemia-guided pre-emptive treatment with ganciclovir after allogeneic stem transplantation : a single-center experience

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.

Lower respiratory tract respiratory virus infections increase the risk of invasive aspergillosis after a reduced-intensity allogeneic hematopoietic SCT

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.

Cytomegalovirus infection and disease after reduced intensity conditioning allogeneic stem cell transplantation: single-centre experience

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.

Pulmonary enterovirus infections in stem cell transplant recipients

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.

Impact of Epstein Barr virus-related complications after high-risk allo-SCT in the era of pre-emptive rituximab

We monitored 133 high-risk allo-SCT recipients for 6 months after transplant for EBV reactivation by quantitative real-time PCR. Rituximab was given as pre-emptive therapy for viremia >1000 copies/mL. The 1-year cumulative incidence of EBV reactivation was 29.4% (95% confidence interval (CI): 18–40) in patients monitored due to initial high-risk characteristics (n=93) and 31.8% (95% CI: 19.7–44) in those followed because of the development of refractory GVHD (n=40). Overall response rate to Rituximab was 83%. Nine patients (9.6%) developed post-transplant lymphoproliferative disorder (PTLD) at a median of +62 days after SCT. Eight of them showed a concomitant CMV reactivation. Second SCT was the only risk factor associated with EBV infection and PTLD in multivariate analysis (hazard ratio (HR) 2.6 (95% CI: 1.1–6.4; P=0.04) and HR 6.4 (95%CI: 1.3–32; P=0.02)). The development of EBV reactivation was not associated with non-relapse mortality or OS (P=0.97 and P=0.84, respectively).

Combining cell lines to optimize isolation of human enterovirus from clinical specimens: Report of 25 years of experience†

Cell culture is still the gold standard for the diagnosis of human enteroviruses (HEVs) although molecular techniques are required for detection of some serotypes. Due to the diversity of HEVs, a single cell line is not susceptible to all serotypes, and several lines are required to optimize the isolation of HEVs. In this study, the results of HEV isolation during the last 25 years are reported. A total of 1,192 HEVs were isolated and isolation rates varied depending on the cell line used. MRC5 cells yielded the best results (70.7%), followed by A549 cells (52.6%), RD cells (37.5%), and HEp‐2 cells (29.7%). A total of 521 HEVs were characterized, and HEV‐B was the most frequent species (81%). Polioviruses (PV) and HEV‐A were isolated less frequently (17% and 1%, respectively). None of the cell lines detected all the enteroviruses. MRC5 cells were the most susceptible for isolation of echoviruses (85.7%) and PVs (85.4%), whereas HEp2 was the most susceptible for Coxsackieviruses B (82.6%). Some serotypes were isolated in one cell line only. 40.5% of echoviruses were isolated in MRC5 cells whereas 42.3% and 23.9% of Coxsackieviruses B were isolated in RD cells and HEp2 cells, respectively. Although A549 cells did not achieve the best performance for any enterovirus serotypes, they isolated 52.6% of the total HEVs. In view of these results, MRC5 cells, A549 cells, and RD cells should be combined to optimize isolation of HEVs. J. Med. Virol. 85:116–120, 2012.

Disseminated Cytomegalovirus Infection in an Immunocompetent Adult Successfully Treated with Ganciclovir

We report the case of a previously healthy man who suffered a disseminated cytomegalovirus infection. He presented with prolonged fever, weight loss of 8 kg, anicteric hepatitis, upper digestive tract bleeding from gastric ulcers, acute polyneuritis and bilateral retinitis. Immunodeficiency was not detected either during admission or during a 3-year follow-up period. The patient was treated with ganciclovir (5 mg/kg BID) during 4 weeks with a favourable clinical outcome. To our knowledge, this is the first reported case with such characteristics.