Rocio Parody

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.

Early Detection of Toxoplasma Infection by Molecular Monitoring of Toxoplasma gondii in Peripheral Blood Samples after Allogeneic Stem Cell Transplantation

BACKGROUND Isolated case reports have shown that recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who develop toxoplasmosis may have circulating Toxoplasma gondii DNA in peripheral blood before the onset of clinical symptoms. METHODS We prospectively studied 106 T. gondii-seropositive adult recipients of HSCTs for the incidence of reactivation of toxoplasmosis in the first 6 months after transplantation. Toxoplasmosis infection (TI) was defined by a positive result of polymerase chain reaction (PCR) of peripheral blood specimens, whereas toxoplasmosis disease (TD) was defined as an invasive infection. RESULTS The incidence of TI was 16% (95% confidence interval [CI], 8%-21%), whereas the incidence of TD was 6% (95% CI, 1%-10%). In the 16 patients with TI, the incidence of disease was 38%, whereas it was 0% in patients without TI (P<.0001). In most patients, the onset of TD or treatment for TI was preceded by an increase in the parasite load in peripheral blood samples, as determined by quantitative PCR. CONCLUSIONS Toxoplasmosis occurs more commonly after HSCT than has previously been suggested, and routine PCR testing of peripheral blood specimens may be an appropriate tool for guiding preemptive therapy in patients at very high risk of developing invasive disease.

Blastoschizomyces capitatus Infection in Patients with Leukemia: Report of 26 Cases

Twenty-six cases of Blastoschizomyces capitatus infection were diagnosed in 25 patients at 7 tertiary care hematology units in Spain over a 10-year period. Most patients (92%) had acute leukemia and developed infection during a period of severe and prolonged neutropenia. Two patients had esophagitis, and the rest had invasive infection. Fungemia (20 cases) was a common finding, with frequent visceral dissemination. The 30-day mortality associated with this infection was 52%, compared with 57% among patients with systemic infection. In a univariate analysis, the following 3 variables had a positive impact on 30-day survival: removal of the central venous catheter within 5 days after the onset of infection (P=.02), a good performance status (P=.003), and receipt of systemic prophylactic or empirical antifungal therapy before infection onset (P=.006). Outcome for neutropenic patients with B. capitatus infection is still poor. Rapid removal of the central venous catheter and novel antifungal therapies are recommended for treatment of this rare infection.

Predicting survival in adults with invasive aspergillosis during therapy for hematological malignancies or after hematopoietic stem cell transplantation: Single-center analysis and validation of the Seattle, French, and Strasbourg prognostic indexes.

In this retrospective monocenter study, we analyzed the outcomes of 130 adult hematological patients who developed a proven (n = 23), probable (n = 71), and possible (n = 36) invasive aspergillosis (IA) in a 13‐year period. Forty‐nine patients (38%) were recipients of an allogeneic hematopoietic stem cell transplantation (AlloHSCT). The main goal of the study was the identification of prognostic factors for 4‐month aspergillosis free survival (AFS) and overall survival (OS). IA was identified as the main cause of death in 27/49 recipients of an AlloHSCT (55%) and 28/81 nontransplanted patients (35%). Diagnosis of IA at or before 2000 had a negative impact in both 4‐month AFS and 4‐month OS in the entire group. In multivariate analysis performed separately for nontransplanted and allo‐HSCT patients, five variables (excluding the year of diagnosis) decreased 4‐month AFS: (i) impairment of one organ function (OF), (ii) impairment of two or more OFs (two points), (iii) disseminated IA, (iv) neutropenia lasting more than 10 days (non‐AlloHSCT group only) or monocytopenia (<0.1 × 109/l) [AlloHSCT group only], and (v) high‐dose steroids (non‐AlloHSCT group only) or an alternative donor (AlloHSCT group only). According to the number of adverse risk factors, three prognostic subgroups were defined in non‐transplanted and alloHSCT patients with good (97% and 78% AFS), intermediate (73% and 32% AFS) and poor prognosis (20% and 11% AFS) of IA [P < 0.01]. In addition, we validated the French and Seattle prognostic indexes for allo‐HSCT recipients and the Strasbourg model for all hematological patients with IA. Am. J. Hematol., 2009.

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.

Patterns of Infection in Patients With Myelodysplastic Syndromes and Acute Myeloid Leukemia Receiving Azacitidine as Salvage Therapy. Implications for Primary Antifungal Prophylaxis

Incidence, etiology, and outcome of infectious episodes in patients with myeloid neoplasms receiving azacitidine are uncertain, with no prospective data available in this group of patients. The aim of the current study was to analyze the incidence and factors related to the probability of infection in a cohort of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with azacitidine who did not receive any type of antimicrobial prophylaxis. Significantly, the group of patients who received prior intensive chemotherapy had more infectious episodes (P = 10(-4)), and particularly, invasive aspergillosis (P = .015), than patients who received frontline azacitidine. Primary antifungal prophylaxis might be recommended in MDS and AML patients receiving azacitidine as salvage therapy after intensive regimens.

The combination of sirolimus plus tacrolimus improves outcome after reduced-intensity conditioning, unrelated donor hematopoietic stem cell transplantation compared with cyclosporine plus mycofenolate

Different types of graft-versus-host disease prophylaxis have been proposed in the setting of reduced intensity and non-myeloablative allogeneic stem cell transplantation. An alternative combination with sirolimus and tacrolimus has recently been tested although comparative studies against the classical combination of a calcineurin inhibitor and mycophenolate mofetil or methotrexate are lacking. We describe the results of a prospective, multicenter trial using sirolimus + tacrolimus as immunoprophylaxis, and compare this approach with our previous experience using cyclosporine + mycophenolate in the setting of unrelated donor transplantation setting after reduced-intensity conditioning. Forty-five patients received cyclosporine + mycophenolate between 2002 and mid-2007, while the subsequent 50 patients, who were transplanted from late 2007, were given sirolimus + tacrolimus. No significant differences were observed in terms of hematopoietic recovery or acute graft-versus-host disease overall, although gastrointestinal acute graft-versus-host disease grade ≥2 was more common in the cyclosporine + mycophenolate group (55% versus 21%, respectively, P=0.003). The 1-year cumulative incidence of chronic graft-versus-host disease was 50% versus 90% for the patients treated with the sirolimus- versus cyclosporine-based regimen, respectively (P<0.001), while the incidence of extensive chronic disease was 27% versus 49%, respectively (P=0.043). The 2-year non-relapse mortality rate was 18% versus 38% for patients receiving the sirolimus- versus the cyclosporine-based regimen, respectively (P=0.02). The event-free survival and overall survival at 2 years were 53% versus 29% (P=0.028) and 70% versus 45% (P=0.018) among patients receiving the sirolimus- versus the cyclosporine-based regimen, respectively. In conclusion, in the setting of reduced intensity transplantation from an unrelated donor, promising results can be achieved with the combination of sirolimus + tacrolimus, due to a lower risk of chronic graft-versus-host disease and non-relapse mortality, which translates into better event-free and overall survival rates, in comparison with those achieved with cyclosporine + mycophenolate. This trial was registered at www.clinicaltrials.gov as 2007-006416-32 by GEL-TAMO/GETH.

Clinical Prognostic Factors for Survival and Risk of Progression to Acute Myeloid Leukemia in Patients With Myelodysplastic Syndromes With 10% Marrow Blasts and Non-Unfavorable Cytogenetic Categories

UNLABELLED Prognosis of myelodysplastic syndromes (MDS) is an area of ongoing interest. Identification of patients with poor outcome in the categories of lower risk disease is critical. In this study, we classify a cohort of 332 lower risk MDS into 3 groups with differences in survival and risk for leukemic progression that could drive treatment approaches to improve prognosis in a fraction of these patients. BACKGROUND Prognosis of MDS and particularly in patients categorized as lower risk (< 10% blasts or low and intermediate-1 International Prognostic Scoring System [IPSS]) is very heterogeneous and includes patients with very different outcomes with current scoring systems. Recently, a new cytogenetic classification has been proposed for the revised IPSS in predicting the outcome for MDS. PATIENTS AND METHODS To evaluate the prognostic significance of multiple variables for survival and risk of progression to acute myeloid leukemia, we analyzed baseline characteristics of 332 lower risk MDS patients within the lower risk cytogenetic categories by IPSS and the recent proposal for the new cytogenetic classification. RESULTS In multivariate analysis, severity of cytopenias, age > 60 years, bone marrow blasts (5%-9%) and transfusion dependency significantly influenced outcome. The combination of these variables allowed development of a model which categorizes patients in 3 different groups with median survival of 95, 44, and 13 months for groups 1, 2, and 3, respectively (P < .001). In addition, this score also stratified patients for their risk for leukemic progression, estimated at 2 years in 3.1%, 7.6%, and 21.3% for each group (P = .024). CONCLUSION Although karyotype remains the main prognostic factor in MDS, the current study identifies clinical parameters predicting outcome among patients with the better cytogenetic profile. Degree of cytopenias, blasts 5%-9% and transfusion dependence might identify a subset of patients within the nonadverse karyotype, in which early or more aggressive approaches could possibly be required to improve survival or prevent disease progression.

Fungal and viral infections after allogeneic hematopoietic transplantation from unrelated donors in adults: improving outcomes over time.

Umbilical cord blood (CB) is increasingly used as an alternative source of stem cells in adult unrelated transplantation. Although registry studies report similar overall outcomes in comparison with BM/PB, comparative studies focusing on severe infections and infection-RM (IRM) with a long follow-up are scarce. A total of 434 consecutive unrelated transplants (1997–2009) were retrospectively analyzed to compare overall outcomes, incidence and risk factors of severe viral and invasive fungal infections in CB (n=65) vs BM/PB recipients (n=369). The 5-year OS was 38 vs 43%, respectively (P=0.2). CB transplantation (CBT) was associated with a higher risk of invasive aspergillosis (100-days-cumulative incidence 16 vs 6%, P=0.04) and CMV infection without differences in RM. No statistically significant differences were found regarding NRM (NRM of 38% in CB vs 37% in BM/PB at 1 year) nor IRM (30% in CB vs 27% in BM/PB at 1 year). In the overall population, NRM and IRM improved in more recent years. In adults who receive a single CBT, the risk of severe infections is increased when compared with unrelated BM/PB recipients, but mortality from infections is similar, leading to similar NRM and survival.

Efficacy and toxicity of intermediate-dose amphotericin B lipid complex as a primary or salvage treatment of fungal infections in patients with hematological malignancies.

We treated 74 adults with a hematological malignancy and documented or suspected invasive fungal infection (IFI) with amphotericin B lipid complex (ABLC) at 3 mg/kg/day. Forty-five patients (61%) received upfront therapy and 29 patients (39%) received salvage therapy for their IFI. Forty-eight of 71 evaluable patients responded [complete responses in 40 (56%) and partial responses in 8 (11%)] and 15 (21%) died as a consequence of the IFI. Response rates in invasive aspergillosis were 33 out of 49 (67%) for probable/definite cases and 6 out of 11 (55%) for invasive candidiasis. In 40 patients with neutropenia-associated IFI, rapid neutropenic recovery ( < 10 days from study entry) was essential for response to therapy (90% vs. 32%, P < 0.01). Treatment was well tolerated, with 15% infusions followed by infusion-related adverse events, nephrotoxicity in 7% of patients and 11% of withdrawals due to toxicity. These data suggest that intermediate-doses of ABLC may be of similar efficacy than higher doses with less toxicity, making it a cost-effective alternative worthy of study in future trials.