Lara Bashoura

Outcome of alveolar hemorrhage in hematopoietic stem cell transplant recipients

Alveolar hemorrhage (AH) is a frequent, serious complication of hematopoietic stem cell transplantation (HSCT). To study the incidence of AH, its clinical course and outcomes in HSCT patients, a retrospective review of the records of all adult patients who underwent bronchoscopy between January 1, 2002 and December 31, 2004 was carried out and those who underwent bronchoscopy after HSCT identified. A total of 223 patients underwent bronchoscopy after HSCT for diffuse pulmonary infiltrates with respiratory compromise. Eighty-seven (39%) patients had AH. Of these, 53 had AH without any identified organism while 34 had an organism along with hemorrhage on bronchoalveolar lavage (BAL). Six-month survival rate of patients with AH was 38% (95% confidence interval: 27–48%). In 95 of the 223 patients, an organism was isolated from BAL. These patients had poor outcomes compared to patients in whom no organism was identified. Patients with both AH and an organism had the worst prognosis. Mortality of patients with AH is improving and long-term survival of patients with AH is feasible. Isolation of a microbial organism in BAL is a strong predictor of poor outcome.

Quality-Adjusted Survival Following Treatment of Malignant Pleural Effusions With Indwelling Pleural Catheters

BACKGROUND Malignant pleural effusions (MPEs) are a frequent cause of dyspnea in patients with cancer. Although indwelling pleural catheters (IPCs) have been used since 1997, there are no studies of quality-adjusted survival following IPC placement. METHODS With a standardized algorithm, this prospective observational cohort study of patients with MPE treated with IPCs assessed global health-related quality of life using the SF-6D to calculate utilities. Quality-adjusted life days (QALDs) were calculated by integrating utilities over time. RESULTS A total of 266 patients were enrolled. Median quality-adjusted survival was 95.1 QALDs. Dyspnea improved significantly following IPC placement (P < .001), but utility increased only modestly. Patients who had chemotherapy or radiation after IPC placement (P < .001) and those who were more short of breath at baseline (P = .005) had greater improvements in utility. In a competing risk model, the 1-year cumulative incidence of events was death with IPC in place, 35.7%; IPC removal due to decreased drainage, 51.9%; and IPC removal due to complications, 7.3%. Recurrent MPE requiring repeat intervention occurred in 14% of patients whose IPC was removed. Recurrence was more common when IPC removal was due to complications (P = .04) or malfunction (P < .001) rather than to decreased drainage. CONCLUSIONS IPC placement has significant beneficial effects in selected patient populations. The determinants of quality-adjusted survival in patients with MPE are complex. Although dyspnea is one of them, receiving treatment after IPC placement is also important. Future research should use patient-centered outcomes in addition to time-to-event analysis. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01117740; URL: www.clinicaltrials.gov.

Pleural effusions in patients with acute leukemia and myelodysplastic syndrome

Abstract Pleural effusions are rarely observed in patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN). Therefore the underlying etiology of pleural effusions and the efficacy and safety of pleural procedures in this population has not been well studied. In a retrospective review of cases from 1997 to 2007, we identified 111 patients with acute leukemia or MDS/MPN who underwent pleural procedures. Clinical characteristics were reviewed, and survival outcomes were estimated by Kaplan–Meier methods. A total of 270 pleural procedures were performed in 111 patients (69 AML, 27 ALL, 15 MDS/MPN). The main indications for pleural procedures were possible infection (49%) and respiratory symptoms (48%), and concomitant clinical symptoms included fever (34%), dyspnea (74%), chest pain (24%) and cough (37%). Most patients had active disease (61%). The most frequent etiology of pleural effusions was infection (47%), followed by malignancy (36%). Severe thrombocytopenia (platelet count < 20 × 103/µL) was present in 43% of the procedures, yet the procedural complication rate was only 1.9%. Multivariate analysis revealed that older age, AML, MDS/MPN and active disease status were associated with a shorter median overall survival. Infection and malignant involvement are the most common causes of pleural effusion in patients with acute leukemia or MDS. After optimizing platelet count and coagulopathy, thoracentesis may be performed safely and with high diagnostic yield in this population. Survival in these patients is determined by the response to treatment of the hematologic malignancy.

Sleep-related breathing disorders in patients with tumors in the head and neck region.

BACKGROUND Sleep disturbance is a prominent complaint of cancer patients. Most studies have focused on insomnia and cancer-related fatigue. Obstructive sleep apnea (OSA) has been reported in small studies and case reports. METHODS In a retrospective review of patients who underwent formal sleep evaluation and polysomnography (PSG) from 2006 to 2011, 56 patients with tumors in the head and neck region were identified. Clinical characteristics, sleep-related history, and PSG data were reviewed. RESULTS Most patients had active cancer (80%), and the majority had squamous pathology (68%). Prominent symptoms included daytime fatigue (93%), daytime sleepiness (89%), and snoring (82%). Comorbid conditions primarily included hypertension (46%) and hypothyroidism (34%). Significant sleep-related breathing disorder was noted in 93% of patients, and 84% met clinical criteria for OSA. A male predominance (77%) was noted, and patients were not obese (body mass index <30 kg/m(2) in 52%). The majority of patients (79%) underwent radiation prior to sleep study, of which 88% had OSA, and in the group without prior radiation, 67% had OSA. Adherence to positive airway pressure (PAP) therapy was slightly better when compared with the general population. A subset of patients with persistent hypoxia despite advanced forms of PAP required tracheostomy. Multivariate analysis revealed that patients with active disease and radiation prior to PSG were more likely to have OSA. CONCLUSION Sleep-related breathing disorder was common in patients with tumors in the head and neck region referred for evaluation of sleep disruption, and most met clinical criteria for OSA. Daytime fatigue and sleepiness were the most common complaints. OSA was prevalent in male patients, and most with OSA were not obese. Architectural distortion from the malignancy and/or treatment may predispose these patients to OSA by altering anatomic and neural factors. A heightened clinical suspicion for sleep-related breathing disorder and referral to a sleep specialist would be beneficial for patients with these complaints.

Vandetanib and indwelling pleural catheter for non-small-cell lung cancer with recurrent malignant pleural effusion.

INTRODUCTION/BACKGROUND Non-small-cell lung cancer patients with malignant pleural effusion have a poor overall median survival (4.3 months). VEGF is a key regulator of pleural effusion production. It is unknown if pharmacological inhibition of VEGF signaling modifies the disease course of non-small-cell lung cancer patients with recurrent malignant pleural effusion. We report the final results of a single-arm phase II clinical trial of the VEGF receptor inhibitor, vandetanib, combined with intrapleural catheter placement in patients with non-small-cell lung cancer and recurrent malignant pleural effusion, to determine whether vandetanib reduces time to pleurodesis. PATIENTS AND METHODS Non-small-cell lung cancer patients with proven metastatic disease to the pleural space using pleural fluid cytology or pleural biopsy who required intrapleural catheter placement were eligible for enrollment. On the same day of the intrapleural catheter insertion, the patients were started on a daily oral dose of 300 mg vandetanib, for a maximum of 10 weeks. The primary end point was time to pleurodesis, with response rate as the secondary end point. Exploratory analyses included measurement of pleural fluid cytokines and angiogenic factors before and during therapy. RESULTS Twenty eligible patients were included in the trial. Eleven patients completed 10 weeks of treatment. Median time to pleurodesis was 35 days (95% confidence interval, 15-not applicable). Median time to pleurodesis in the historical cohort was 63 days (95% confidence interval, 45-86) when adjusted for Eastern Cooperative Oncology Group performance status ≤ 2. CONCLUSION Vandetanib therapy was well tolerated; however, it did not significantly reduce time to pleurodesis.

Safety of flexible bronchoscopy, rigid bronchoscopy, and endobronchial ultrasound-guided transbronchial needle aspiration in patients with malignant space-occupying brain lesions

BACKGROUND Bronchoscopy in patients with space-occupying brain lesions is anecdotally felt to carry a high risk of neurologic complications. METHODS We conducted a retrospective cohort study of patients with evidence of a malignant, space-occupying brain lesion who were referred for flexible or rigid bronchoscopy or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The primary outcome of interest was the incidence of neurologic complications following the procedures in these patients. RESULTS Of the 103 enrolled patients, flexible bronchoscopy was performed in 41, rigid bronchoscopy in 12, and EBUS-TBNA in 50. Among these patients, 41 (40%) had evidence suggestive of increased intracranial pressure on imaging. Among all study patients, none (95% CI, 0-0.035) had neurologic, procedure-specific, or sedation-specific complications, and the level of care was not escalated in any of these patients. CONCLUSIONS On the basis of our findings, we recommend that procedures such as flexible or rigid bronchoscopy or EBUS-TBNA in patients with malignant space-occupying brain lesions should be considered reasonably safe as long as neurologic findings are stable.

Detecting Medical Device Complications Lessons From an Indwelling Pleural Catheter Clinic

Safety monitoring after implantation of medical devices is essential throughout a product’s life cycle. A suspected increase in complications related to indwelling pleural catheters led to a 2-part cohort study. Part 1 investigated and corroborated the increase in rate of complications thought to be related to defective catheters. The inability of the standard clinical follow-up to detect such a rise in complication rates for more than 3 months and a 3-fold increase prompted the authors to develop a simple tool to monitor catheter complication rates. This tool, which combined quality control statistics (p-chart) and the existing billing software, was shown to be effective in part 2 of this study. Care center–level active safety assurance monitoring can be of great value because, unfortunately, an independent and impartial safety monitoring organization, which is essential for postmarketing surveillance of any medical device, is still not available.

Critical Airway Obstruction due to Pseudomembranous Aspergillus tracheitis

A 35-year-old woman with recently diagnosed acute leukemia complicated with necrotizing tracheitis due to Aspergillus infection was transferred to our institution complaining of worsening dyspnea. Before presentation she received 28 days of induction chemotherapy with steroids. She developed cough and hoarseness 3 weeks after initiation of chemotherapy and was admitted with neutropenic fever. Laboratory data revealed neutropenia for the past 5 weeks, and sputum culture grew Aspergillus terreus. Aside from empiric antimicrobial therapy, she was treated with voriconazole. Computed tomography of the chest revealed evidence of circumferential thickening of the trachea throughout its course. In addition, curvilinear densities with the appearance of sloughedoff material were seen within the lumen of the trachea (Figures 1A and 1B). The decision was made to proceed with bronchoscopy for airway evaluation. The bronchoscopy demonstrated up to 80% obstruction of the trachea, with white necrotic, but firm, pseudomembranes, secondary to severe tracheitis. The anterior wall of the trachea and the proximal airway were severely destroyed, and cartilaginous rings were visible (Figures 2A and 2B). Therapeutic rigid and flexible bronchoscopy was performed with cryotherapy recanalization and therapeutic aspiration of the sloughed-off material. A 4-cm white piece of tissue was removed (Figure 2C), resulting in residual luminal narrowing of less than 25%. Pathologic examination showed extensive necrosis, with deposition of fungal-hyphae organisms, compatible with Aspergillus infection (Figures 2E and 2F). Immunocompromised patients can develop disseminated pulmonary aspergillosis and rarely necrotizing tracheobronchitis (1). There are a few reports in the literature of airway obstruction, but the condition typically has lethal outcomes. When the bronchus or trachea overlying the pulmonary artery is infected, a fatal hemorrhage can occur if the obstructing mass is manipulated (2). There is no consensus on bronchoscopic management of these patients, and bronchoscopic debridement has only been mentioned in case reports. Our patient was treatedwith inhaled amphotericin B, voriconazole, and caspofungin initially. Due to side effects, this was switched to posaconazole, which led to a complete clinical and radiological response. A bronchoscopy performed a year after diagnosis and before stem cell transplantation showed no evidence of disease (Figure 2D). n

Resolution of Myelofibrosis-Associated Pulmonary Arterial Hypertension following Allogeneic Hematopoietic Stem Cell Transplantation

We present the case of a 62-year-old man with myelofibrosis-associated pulmonary arterial hypertension (PAH) who underwent allogeneic hematopoietic stem cell transplantation with subsequent resolution of disease and PAH. Right heart catheterization was used to guide PAH therapy before and after transplantation. Drug interactions, adverse effects, and renal insufficiency posed clinical challenges for the management of PAH-specific medications after transplantation. PAH improved soon after transplantation, and vasoactive medications were tapered off. Resolution of PAH was confirmed with repeat measurement of pulmonary hemodynamic characteristics. Although the etiology and pathophysiology for the resolution of PAH was unclear, the myelopulmonary pathophysiologic link was likely to have contributed. This is the first report describing resolution of myelofibrosis-associated PAH after allogeneic hematopoietic stem cell transplantation.

Pulmonary Manifestations of Lymphoma and Leukemia

Pulmonary manifestations of lymphoma and leukemia may involve multiple structures within the thoracic cavity. Malignant lymphoma typically originates in lymph nodes, but concomitant or primary presentations with parenchymal, pleural, or tracheobronchial disease may occur. Once infection is excluded, leukemic infiltrates may be related to malignancy, hemorrhage, or secondary pulmonary alveolar proteinosis. Confirmation with cytology or flow cytometry is recommended to diagnose malignant pleural effusions in hematologic malignancies. In chronic leukemia with progressive pulmonary findings, exclusion of a synchronous malignancy or Richter syndrome should be performed. Venous thromboembolism may present in patients with leukemia and lymphoma despite the presence of thrombocytopenia.