Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Signs and Symptoms, Respiratory

Neoplasms by Histologic Type

Hematologic Diseases

Acute Graft Versus Host Disease

All Drugs and Chemicals

Dimercaprol

All patients will receive the lab testing on bronchoscopy specimens

Bronchoalveolar lavage (BAL) with subsequent testing for pathogens

Microbiological analysis

H. Kent Holland, MD

Pulmonary infiltrates frequently complicate the care of hematopoietic stem cell transplant (HSCT) and leukemia patients. Bronchoalveolar lavage (BAL) is frequently used to evaluate new pulmonary infiltrates in this population, however utility is limited by a historically low diagnostic yield for infection.

In an effort to improve diagnostic yields, this study will complete a Fiberoptic Bronchoscopy (FOB) within 8 hours of radiographic documentation of pulmonary infiltrates, prior to initiating new antibiotic therapy. To further improve detection of microbiological pathogens, the study will utilize PCR testing with rapid turnaround time to detect atypical pneumonia (M pneumoniae, C. Pneumonia, Legionella species, and respiratory viruses) and aspergillosis.

Proper diagnosis and prompt treatment favorably impacts survival in the post transplant setting, but is often difficult and frequently results in inappropriate or late therapy. Low yields may be linked with empiric antibody therapy begun prior to the procedure, delayed time to procedure, procedure technique, the presence of graft versus host disease (GVHD), neutropenia, and diffuse infiltrates (as opposed to localized infiltrates or focal masses and nodules). One recent study found that early FOBs (less than or equal to 4 days between detection of pulmonary infiltrates and FOB) were 2.5 times more likely to establish a diagnosis of pneumonia compared to late examinations. Delaying this procedure(greater than 5 days between detection of pulmonary infiltrates and FOB) was associated with drug resistant organisms, polymicrobial infections, and worsened patient prognosis.

FOB in HSCT and Leukemia Patients With Acute Respiratory Symptoms and Pulmonary Infiltrates

A Prospective Assessment of the Diagnostic Utility of Emerging Laboratory Assessments Used in Conjunction With FOB in HSCT and Leukemia Patients With Acute Respiratory Symptoms and Pulmonary Infiltrates

To determine the diagnostic yield related to fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) in hematopoietic stem cell transplant (HSCT) and leukemia patients with acute respiratory symptoms and pulmonary infiltrates utilizing both current standard of care microbiology testing and emerging molecular genetic laboratory assessments.

To correlate specific types of pulmonary infiltrates (focal, multifocal, or diffuse interstitial or alveolar infiltrates) with microbiological findings. Patients were evaluated by changes on the CT and categorized as follows:

1. Air space
2. ground glass/reticular nodular
3. nodular/cavitary
4. single patchy infiltrate

To describe the microbiological findings in HSCT and leukemia patients with fever, respiratory symptoms, and pulmonary infiltrates

Blood and Marrow Transplant Group of Georgia

Northside Hospital, Inc.

All patients will receive the lab testing on bronchoscopy specimens

Microbiological analysis: Bronchoalveolar lavage (BAL) with subsequent testing for pathogens

Laboratory Testing

Patients were treated in an adult center. All patients were over the age of 18.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

All Patients Will Receive Lab Testing on Bronchoscopy Specimen

Number of Patients With Positive Culture or Molecular Results After Brochoscopy

Patients were evaluated by changes on the CT and categorized as follows:

1. Air space
2. ground glass/reticular nodular
3. nodular/cavitary
4. single patchy infiltrate

These were evaluated on CT scans and all units of measure are the same.

Number of Patients With Positive CT Result

Number of Participants With Positive Bacterial Results by PCR

Number of Patients With Positive Fungal Results by PCR

Number of Participants With Positive Viral Results by PCR

Number of Participants With Positive Myocbacteria Results by Culture

Overall Study

Hypoxia

Hematologic Neoplasms

Oxygen is delivered at 50 L/min with FiO2 50% delivered for at least 5 min prior to FOB and throughout the procedure.

Oxygen is delivered at 6L/min applied for at least 5 minutes prior to FOB and throughout the procedure.

High Flow Nasal Cannula or Low Flow Nasal Cannula

Dr. Sangeeta Mehta, MD, FRCPC

Pneumonia is a lung infection. Fiberoptic bronchoscopy is a test to diagnose the type of lung infection. While this procedure is being performed, a small amount of oxygen is delivered into the nose (low flow nasal cannula). Occasionally during this procedure, the blood oxygen of the patient may drop and an intervention such as increasing the oxygen flow, or placing the patient on a breathing machine is required. An alternative device called 'Optiflow' can provide high flow oxygen through nasal cannula, and is comfortable for patients. If Optiflow is used during bronchoscopy, it may prevent the blood oxygen from dropping.

Pneumonia is a lung infection that is a common complication in people with cancer, because of a weak immune system. Fiberoptic bronchoscopy is a test that is commonly used to help doctors diagnose the type of lung infection and treat it appropriately. It involves passing a thin tube with a camera at the end inside the lungs, and taking some fluid samples which are sent for analysis. While this procedure is being performed, a small amount of oxygen is delivered into the nose (low flow nasal cannula). Occasionally during this procedure, the blood oxygen of the patient may drop (even if the patient is receiving oxygen, and especially if the patient has severe pneumonia), and the procedure may have to be interrupted or prematurely stopped. If the oxygen level drops significantly, an intervention such as increasing the oxygen flow, or in the worst-case scenario temporarily placing the patient on a breathing machine is required. An alternative device called 'Optiflow' can provide high flow oxygen through nasal cannula, and is comfortable for patients. Optiflow was approved by Health Canada in 2006, and is commonly used in hospitals in Ontario and around the world to support patients whose blood oxygen is low. If Optiflow is used during bronchoscopy, it may prevent the blood oxygen from dropping.

Patients will be randomized to either HFNC delivered at 50 L/min with FiO2 50% delivered for at least 5 min prior to FOB and throughout the procedure; or to conventional supplemental LFNC delivered at 6L/min applied for at least 5 minutes prior to FOB and throughout the procedure.

Low-Flow vs. High-Flow Nasal Cannula for Hypoxemic Immunocompromised Patients During Diagnostic Bronchoscopy

Low-Flow vs. High-Flow Nasal Cannula for Hypoxemic Immunocompromised Patients During Diagnostic Bronchoscopy: A Randomized Controlled Trial

Any desaturation during FOB or during the 1 hour post-FOB defined as a drop in SpO2 of 4% or more for more than 1 minute or any drop in O2 less than 90%, and necessitating an increase in FiO2 to maintain a saturation ≥92% for at least 1 minute.

Princess Margaret Hospital, Canada

Mount Sinai Hospital, Canada

Professor

Respiratory Tract (Lung and Bronchial) Diseases

Wounds and Injuries

Immune System Diseases

Dyspnea

Acute Lung Injury

Lung Injury

Edema

Pulmonary Edema

Transfusion-Related Acute Lung Injury

Respiration Disorders

Respiratory Tract Diseases

Lung Diseases

Acute Respiratory Distress Syndrome

Idit Matot, MD

Yifat Klein, PhD

Shlomo Dadia, MD

Alex Gorodetsky, MD

Currently Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality in the United States, and one of major post-transfusion complications. TRALI is defined as new ALI occurring within 6 hours from the onset of transfusion. It is manifested by acute dyspnea, hypoxemia and bilateral infiltrates in chest radiograph. TRALI may be caused by any blood product and is not dose-dependent. Associated risk factors include prolonged storage of blood products and underlying conditions such as severe IHD hematologic malignancies or active infections. Since TRALI has only recently been defined as a clinical entity, and its prevalence has been largely underestimated - the epidemiology of TRALI is not well established. Therefore the objective of this work is to study the incidence of TRALI in a patient population that receive blood products frequently, namely orthopedic-oncologic.

Background

The transfusion of blood products is occasionally complicated by acute lung injury (ALI), which can progress to the acute respiratory distress syndrome (ARDS). Such transfusion-related acute lung injury, abbreviated TRALI, has been defined by both a National Heart, Lung, and Blood Institute (NHLBI) working group, and by a Canadian consensus conference (CCC), as new ALI occurring during or within six hours after a transfusion \[1-2\]. This definition is based entirely on clinical and radiological criteria and includes \[2-4\]:

1. ALI, as defined by \[4\]:

   A. The sudden onset of respiratory distress symptoms (dyspnea). B. Hypoxemia: as defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) below 300mmHg, or oxygen saturation (SpO2) below 90% on room air, or other clinical evidence of hypoxemia C. Bilateral infiltrates on frontal chest X-ray, without cardiomegaly. D. No clinical evidence of left atrial hypertension (congestive heart disease).
2. No preexisting ALI before transfusion.
3. During or within 6 hr after transfusion of any blood product.
4. No temporal relationship to an alternative risk factor for ALI. All types of blood products have been associated with TRALI, however, the plasma-rich components, such as fresh frozen plasma (FFP), whole blood, packed red blood cells (PC) and platelets, have been most frequently implicated \[3, 5-10\].

Prolonged storage of transfused products, use of FFP, and the presence of an underlying condition such as recent surgery, cytokine treatment, thrombocytopenia, massive blood transfusion, hematologic malignancies or cardiovascular disease requiring cardiopulmonary bypass (CABG) surgery, and active infection have been reported as risk factors for the development of TRALI \[11-18\].

The pathogenesis of TRALI involves the presence of anti-leukocyte antibodies and/or biologically active lipids from cell membrane fragments (and cytokines) in the donor's blood, triggering an inflammatory response within the recipient's pulmonary microvasculature, which in turn leads to lung injury \[2,13,16,19-27\].

The incidence of TRALI is not well established \[28\]. Nevertheless, using the NHLBI/CCC definition of TRALI, several retrospective studies reported the incidence of TRALI to be one case for every 1000-2400 units transfused \[29-30\]. This incidence estimate of 0.04% to 0.1% (or up to 0.85% among transfused patients) is comparable to other estimates from earlier studies that used older case definitions \[6,12,31\]. The only prospective cohort clinical surveillance study to use current diagnostic guidelines for TRALI reported an 8% incidence of TRALI in their intensive care unit (ICU) \[32\]. These data suggest that passive reporting systems greatly under-estimate the number of TRALI cases.

Even though underdiagnosed, TRALI is currently the leading cause of transfusion-related mortality in the United States \[1,7,11\]. The estimated mortality rate for recognized TRALI is 5%-8% \[20\]. However, most survivors recover completely with appropriate supportive care and can receive additional blood products in the future \[11,20\].

Due to the lacking epidemiology, and the increasing significance of TRALI as a major transfusion-associated complication, we stress the need for additional prospective surveillance studies.

Taken together, we wish to conduct a prospective observative study in order to evaluate the incidence of TRALI among patients undergoing elective orthopedic-oncology procedures. This patients' population receives blood product transfusions frequently, and may thus provide an adequate cohort for such study.

Study Objectives This work aims to study the prevalence of TRALI-associated morbidity and mortality in patients undergoing elective orthopedic-oncology procedures, and are transfused with blood products in the perioperative period.

In addition, we wish to evaluate whether:

A.The incidence of TRALI is higher in patients operated for malignancies (versus benign neoplasms) B.The incidence of TRALI is higher in patients treated with C.chemotherapy/radiation prior to surgery (versus non-treated) The incidence of TRALI is increasing with older blood products

Methods Study design An informed consent will be obtained from all orthopedic-oncology patients scheduled to have an elective surgery, except for those who require minor procedures (e.g., biopsies) which normally do not require transfusions. Diuretics and oral hypoglycemics will be discontinued the day prior to surgery, as dictated by the routines in our patients.

Peri-operative management Anesthetic and surgical management as well as blood product transfusion will adhere to standard practice.

Postoperatively, the patients will be transferred to the post-anaesthesia care unit and later to the orthopedic-oncology department, unless otherwise indicated.

In the postoperative period, departmental routines will guide blood product transfusions, pain management and fluid therapy.

Monitoring of patients who received transfusions

Every patient that receives blood products will be included in the study, whether it occurred pre-operatively, intra-operatively or post-operatively as long as they are hospitalized. For these patients we will document:

A.General demographics, including chronic diseases, medications and treatments (e.g., chemotherapy/radiotherapy).

B.Blood product information, including type, dosage and storage age. C.Intra- and post-operative data, including operative time, volume of crystalloids (and colloids) given during surgery and afterwards, urine output, the need for vasopressors, inotropes or diuretics, re-intubations, transfer to ICU and hospital length of stay (LOS).

For each unit of blood product transfused, we will commence patient monitoring for the next 6 hours. If several units are given in a sequel we will monitor the patient since the beginning of the first transfusion until 6 hours after the last transfusion. Monitoring will include:

1. Clinical symptoms of dyspnea.
2. PaO2/FiO2, or SpO2 on room air if arterial line is not obtainable - every 2 hours or when indicated by clinical signs.

   2.1. If PaO2/FiO2\< 300mmHg, or SpO2\< 90% on room air, or clinical signs of lung injury occur - chest X-ray will be obtained and diagnosed by two radiologists.
3. Hb (gr/dl) will be assessed according to the physician's decision.

Study size In the orthopedic-oncology department of Tel Aviv Sourasky Medical Center approximately 550 patients are operated annually, about 20% of whom receive transfusions. Accordingly, the study is planned for 5 years. Therefore the anticipated sample size is approximately 550 patients.

blood from arterial line to test for PaO2

The Incidence of TRALI in Patients Undergoing Orthopedic-Oncology Surgery

The Incidence of Transfusion-Related Acute Lung Injury (TRALI) Following Blood Product Transfusion in Patients Undergoing Elective Orthopedic-Oncology Procedures

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
FOB in HSCT and Leukemia Patients With Acute Respiratory Symptoms and Pulmonary Infiltrates	NCT01328873	Pulmonary Infil...	Microbiological...	18 Years - 80 Years	Northside Hospital, Inc.
Low-Flow vs. High-Flow Nasal Cannula for Hypoxemic Immunocompromised Patients During Diagnostic Bronchoscopy	NCT03168815	Immunocompromis... Hematologic Mal... Post Hematopoie... Hypoxia Pulmonary Infil...	High Flow Nasal...	18 Years -	Mount Sinai Hospital, Canada
The Incidence of TRALI in Patients Undergoing Orthopedic-Oncology Surgery	NCT00914784	Dyspnea Pulmonary Edema		18 Years - 90 Years	Tel-Aviv Sourasky Medical Center

Spots Global Cancer Trial Database for pulmonary infiltrates