Characteristics and outcome of respiratory syncytial virus infection in patients with leukemia.

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Torres HA, Aguilera EA, Mattiuzzi GN, Cabanillas ME, Rohatgi N, Sepulveda CA, Kantarjian HM, Jiang Y, Safdar A, Raad II, Chemaly RF.

Haematologica. 2007 Sep;92(9):1216-23. Epub 2007 Aug 1.

Abstract

BACKGROUND AND OBJECTIVES:

Little is known about respiratory syncytial virus (RSV) infection in patients with leukemia. The aim of this study was to determine the characteristics, and the outcome of RSV infection with or without therapy with aerosolized ribavirin in leukemia patients.

DESIGN AND METHODS:

We reviewed the records of 52 leukemia patients with RSV infection seen at our institution between October 2000 and March 2005.

RESULTS:

The median age of the patients was 47 years (range, 1-83 years). Most patients were male (65%) and had acute leukemia (65%); 46% had received salvage chemotherapy and 62% corticosteroids before RSV infection. Compared to the 25 patients with upper respiratory tract infection (URI), the 27 patients with pneumonia had a higher median APACHE II score at the time of the first assessment at the hospital for respiratory symptoms (11 vs 16), and a higher rate of corticosteroid treatment in the month preceding the infection (48% vs 74%) (all p < or =0.05). Twenty-four (46%) patients received aerosolized ribavirin. Patients who presented with URI and were treated with ribavirin were less likely than non-treated patients to develop pneumonia (68% vs 96%, p<0.01) and possibly die of pneumonia (6% vs 36%, p=0.1). Multiple logistic regression analysis identified high APACHE II score and lack of ribavirin treatment as independent predictors of progression to pneumonia (p=0.01). Five patients (10%) died within 30 days of RSV infection; all had pneumonia.

INTERPRETATION AND CONCLUSIONS:

RSV infection is associated with significant morbidity and mortality in leukemia patients; treatment with aerosolized ribavirin at the stage of URI may prevent pneumonia in some subsets of patients.

Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation.

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Bashoura L, Gupta S, Jain A, Couriel DR, Komanduri KV, Eapen GA, Safdar A, Broglio KR, Adachi R, Dickey BF.

Bone Marrow Transplant. 2008 Jan;41(1):63-7. Epub 2007 Oct 15.

Abstract

Post transplantation constrictive bronchiolitis (PTCB) is the most common pulmonary complication among long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT). It is a late manifestation of GVHD. Its treatment with high-dose systemic corticosteroids and other immunosuppressive regimens is associated with multiple side effects. Topical corticosteroids are used for the treatment of other manifestations of GVHD to minimize these side effects. We conducted a retrospective analysis of a series of adult patients to evaluate the efficacy of high-dose inhaled corticosteroids in the treatment of PTCB. Seventeen patients with new-onset airflow obstruction were diagnosed with PTCB. Their forced expiratory volume in 1 s (FEV1) declined from a median of 84% (range, 56-119) before HSCT to 53% (26-82) after HSCT. All patients received inhaled fluticasone propionate 500-940 microg two times daily. Symptoms of airway obstruction improved and FEV1 stabilized 3-6 months after treatment. We conclude that high-dose inhaled corticosteroids may be effective in the treatment of PTCB and propose a plausible mechanism of its action. A prospective evaluation of its efficacy is warranted.

Dose-related safety and immunogenicity of baculovirus-expressed trivalent influenza vaccine: a double-blind, controlled trial in adult patients with non-Hodgkin B cell lymphoma.

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Safdar A, Rodriguez MA, Fayad LE, Rodriguez GH, Pro B, Wang M, Romaguera JE, Goy AH, Hagemeister FB, McLaughlin P, Bodey GP, Kwak LW, Raad II, Couch RB.

J Infect Dis. 2006 Nov 15;194(10):1394-7. Epub 2006 Oct 6.

Abstract

In 27 patients randomized to receive commercial trivalent influenza vaccine (TIV) containing 15 microg of the hemagglutinin (HA) of influenza A (H3N2 and H1N1) and B virus or a recombinant vaccine (rHAO) containing 15, 45, or 135 microg of each HA, reactogenicity was minor. Among patients with similar prevaccination titers, 40% given 45 microg and 60% given 135 microg of rHAO developed an increase in influenza A/H3 neutralizing antibody levels; there were no increases in 4 given TIV. For each vaccine, the highest frequencies of increases in neutralizing antibody levels and the highest mean titers occurred in those given the 135- microg vaccine.

Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center.

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Chemaly RF, Ghosh S, Bodey GP, Rohatgi N, Safdar A, Keating MJ, Champlin RE, Aguilera EA, Tarrand JJ, Raad II.

Medicine (Baltimore). 2006 Sep;85(5):278-87.

Abstract

Community respiratory viruses (CRVs) have been recognized as a potential cause of pneumonia and death among hematopoietic stem cell transplantation (HSCT) recipients and patients with hematologic malignancies. We reviewed the Microbiology Laboratory records dated from July 1, 2000, to June 30, 2002, to identify patients who had respiratory specimens positive for influenza, parainfluenza, respiratory syncytial virus, or picornavirus. We identified 343 infections among patients with underlying hematologic malignancies and HSCT. We collected data on type of disease, age, sex, type of infection, neutrophil and lymphocyte counts, therapy, and outcome. Influenza, parainfluenza, and respiratory syncytial virus accounted for most cases and were approximately equal in frequency. Most infections occurred predominantly among recipients of allogeneic transplants. Infection progressed to pneumonia in 119 patients (35%) and occurred with similar frequency for the 3 viruses. Patients at greatest risk for developing pneumonia included those with leukemia, those aged more than 65 years, and those with severe neutropenia or lymphopenia. Lack of respiratory syncytial virus-directed antiviral therapy (p=0.025) and age (p=0.042) were associated with development of respiratory syncytial virus pneumonia, and an absolute lymphocyte count<or=200 cells/mL (p=0.049) was associated with development of influenza pneumonia. The overall mortality rate for CRV pneumonia was 15%. The only independent predictor of fatal outcome was an absolute lymphocyte count<or=200 cells/mL (p=0.03) in patients with influenza pneumonia.HSCT recipients and patients with hematologic malignancies who develop upper respiratory infection due to CRVs should be considered for antiviral therapy of proven efficacy to reduce the risk of pneumonia and death.

Rosai-Dorfman disease misdiagnosed as active tuberculosis.

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Safdar A, Gillenwater AM, Jones DM, Jorgensen JL, Romaguera JE.

Leuk Lymphoma. 2006 Jul;47(7):1441-2.

Strategies to enhance immune function in hematopoietic transplantation recipients who have fungal infections.

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Safdar A.

Bone Marrow Transplant. 2006 Sep;38(5):327-37. Review.

Abstract

The challenges in the treatment of systemic fungal infections after HSCT include: (1) changing epidemiology as less drug-susceptible saprophytic fungi are increasingly associated with human disease; (2) the difficulty of early and correct diagnosis, even with the new generation of enzymatic immunoassays; (3) the inability to reduce or eliminate predisposing factors, especially severe immune suppression in most transplant patients with these infections and (4) the uncertain role of antifungal drug combinations and risk of drug antagonism complicating effective empiric-pre-emptive therapy. Current, developing and future immune enhancement strategies including recombinant granulocyte- and granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-gamma (IFN-gamma), adjuvant pro-inflammatory cytokine therapy during mobilized donor granulocyte transfusions, therapeutic potential of pentraxin, adaptive immune transfer and dendritic cell fungal vaccines. Improved understanding of the molecular pathogenesis of fungal infections and of the complexity of host antifungal immune responses has provided the critical information to readdress existing treatment paradigms and further evaluate the role of GM-CSF and IFN-gamma early in the course of therapy against life-threatening fungal infections in high-risk patients following stem cell transplantation.

Changing trends in etiology of bacteremia in patients with cancer.

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Safdar A, Rodriguez GH, Balakrishnan M, Tarrand JJ, Rolston KV.

Eur J Clin Microbiol Infect Dis. 2006 Aug;25(8):522-6.

Abstract

The present study was conducted to determine trends in the quantitative bacterial load patterns of bacterial bloodstream infections (BSI) caused by various bacteria in patients receiving care at a comprehensive cancer center. Bacterial loads of all consecutive quantitative blood cultures performed during 1998 and 2004 were graded quantitatively. Gram-positive bacteria (GPB) were responsible for the majority of BSI episodes in both years studied: 740 of 1,055 (73%) in 1998 and 820 of 1,025 (82%) in 2004. Compared with GPB infections, a significant proportion of infections caused by Gram-negative bacteria was associated with a high bacterial load (HBL) (11 vs 28% in 1998 and 10 vs 30% in 2004; p<0.001). In 2004, BSI episodes due to non-Pseudomonas non-fermentative GNB (Stenotrophomonas maltophilia and Acinetobacter spp) were significantly associated with a HBL compared to BSI due to Pseudomonas aeruginosa (47 vs 23%; p<0.05); this was not the case in 1998. Conversely, the HBLs commonly associated with BSI due to Staphylococcus aureus (50%) and Streptococcus spp (35%) versus coagulase-negative staphylococci (13%; p<0.0001) during 1998 were not noted during 2004 (22% Staphylococcus aureus, 20% Streptococcus spp, 21% coagulase-negative staphylococci; p>0.5). The spectrum of BSI continues to change and its prognostic implications in cancer patients needs further study.

Nocardia veterana bloodstream infection in a patient with cancer and a summary of reported cases.

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Ansari SR, Safdar A, Han XY, O’Brien S.

Int J Infect Dis. 2006 Nov;10(6):483-6. Epub 2006 Jul 28.

Fungal osteoarticular infections in patients treated at a comprehensive cancer centre: a 10-year retrospective review.

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Kumashi PR, Safdar A, Chamilos G, Chemaly RF, Raad II, Kontoyiannis DP.

Clin Microbiol Infect. 2006 Jul;12(7):621-6.

Abstract

This study reviewed retrospectively the clinical characteristics of 28 cancer patients with fungal osteoarticular infections (FOAIs) between 1995 and 2005. Most patients (26; 93%) had haematological malignancies (19 had leukaemia); half (14) were allogeneic stem-cell transplant recipients. Twelve patients (43%) had severe neutropenia (< or = 100/mm3) with a mean duration of 65 days (range 10-500 days), and ten (36%) patients had received a significant dose of corticosteroids. Most (19; 68%) FOAIs were caused by contiguous extension, while nine (32%) were associated with haematogenous spread. Pain, joint instability and local drainage were seen in 28 (100%), six (21%), and seven (25%) patients, respectively. Sixteen (57%) patients had symptoms for < 1 month. The sinuses (ten; 36%) and the vertebral spine (six; 21%) were the most common sites involved. Moulds were the predominant pathogens: Aspergillus fumigatus (two); non-fumigatus Aspergillus spp. (eight); non-specified Aspergillus spp. (three); Fusarium spp. (six); Zygomycetes (five); Scedosporium apiospermum (two); and Exserohilum sp. (one). Candida was the causative pathogen in four cases (including two cases of mixed FOAIs). Arthritis and post-operative FOAIs were both uncommon manifestations, occurring in two patients each. All patients received systemic antifungal therapy (combinations in 20 cases), and 19 cases underwent adjunctive surgery. The crude mortality rates (at 12 weeks) were 44% (9/20) in the patients who underwent surgery and antifungal therapy vs. 33% (2/6) in patients who received antifungal therapy alone (p not significant). FOAI is a rare, yet severe, manifestation of localised or systemic mycoses, caused predominantly by moulds, and is seen typically in patients with haematological malignancies.

Influence of type of cancer and hematopoietic stem cell transplantation on clinical presentation of Pneumocystis jiroveci pneumonia in cancer patients.

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Torres HA, Chemaly RF, Storey R, Aguilera EA, Nogueras GM, Safdar A, Rolston KV, Raad II, Kontoyiannis DP.

Eur J Clin Microbiol Infect Dis. 2006 Jun;25(6):382-8.

Abstract

Pneumocystis jiroveci pneumonia is a common infection in patients with AIDS but an infrequent cause of pneumonia in cancer patients. Little is known about the impact of cancer type and hematopoietic stem cell transplantation on the presentation and outcome of P. jiroveci pneumonia in cancer patients. A retrospective cohort study of all patients with cancer and P. jiroveci pneumonia cared for at The M.D. Anderson Cancer Center during 1990-2003 was conducted. Eighty episodes of P. jiroveci pneumonia in 79 patients were identified. In most (67%) episodes, patients had a hematologic malignancy. In 23 (29%) episodes, patients had undergone hematopoietic stem cell transplantation. Twenty-seven percent of patients with histopathologically confirmed P. jiroveci pneumonia had nodular infiltrates on the radiographic study. Pleural effusion and pneumothorax were more common in patients with hematopoietic stem cell transplantation than in those with solid tumors. Clinical suspicion of P. jiroveci pneumonia was less common in patients with nodular infiltrates than in those without such a radiographic finding (7 vs. 39%; p=0.002). Twenty-six of 76 (34%) patients with data available died of P. jiroveci pneumonia. Predictors of death by univariate analysis included older age, tachypnea, high APACHE II score, use of mechanical ventilation or vasopressors, lower arterial pH level, absence of interstitial component, pneumothorax, and comorbid conditions (all p<0.05). Multivariate analysis identified the use of mechanical ventilation as an independent predictor of death. Death attributable to P. jiroveci pneumonia appeared to be higher in patients with hematopoietic stem cell transplantation. The clinical presentation of P. jiroveci pneumonia in cancer patients may be affected by the category of cancer and the history of hematopoietic stem cell transplantation. P. jiroveci pneumonia remains a rare yet severe infection in cancer patients.