DIAGNOSTIC VALUE OF BRONCHOALVEOLAR LAVAGE IN LEUKEMIC AND BONE MARROW TRANSPLANT PATIENTS: THE IMPACT OF ANTIMICROBIAL THERAPY

Background

Pneumonia carries significant morbidity and mortality in leukemic and bone marrow transplant patient.  The development of pulmonary infiltrates in the setting of such immunocompromise raises concern for both infectious and non-infectious etiologies, some of which are potentially treatabl.  Performing bronchoscopy provides several different options for sampling the lower respiratory tract.  Among these, bronchoalveolar lavage (BAL) is especially effective at collecting samples from the alveoli and has been shown to be associated with less risk than transbonchial biops. We sought to examine the effect of antimicrobial treatment on BAL results in a large study population of leukemic and bone marrow transplant patients.

Subjects and Methods

This retrospective chart review was performed at a single academic cancer center.  A power analysis was performed to determine the appropriate sample size. The patients were selected from those who had undergone an inpatient bronchoscopy in reverse chronological order until 300 patients with either a hematopoietic stem cell transplant or hematologic malignancy were identified.  The exclusion criteria were age <18, a diagnosis of HIV or acquired immune deficiency syndrome (AIDS), or outpatient status.  Electronic medical records were reviewed and data extracted by a single investigator, CY.  Data including age, sex, cancer diagnosis, time from HSCT, leukocyte count, neutropenia in addition to medications were collected.  A normal white blood cell (WBC) count was considered 4,000-12,000/mm³.  Neutropenia was defined as an absolute neutrophil count (ANC) less than 500/mm³.  Medications including antibiotic duration and timing, antifungal use, immunosuppressant use or glucocorticoids were recorded. A positive BAL yield was defined as the culture identification of at least one organism known to be pathogenic in this patient population.  Candida species and coagulase negative staphylocci were considered colonizers The bronchoscopy technique and procedure was similar for each patient, utilizing a Fujinon 470S bronchoscope for every procedure The BAL specimens were collected without suction connected to the bronchoscope prior to a systematic airway survey.  The BAL was performed by instilling two 60cc aliquots of room temperature sterile 0.9% saline followed by slow manual aspiration. Correlates of a positive BAL yield and time on antibiotics were initially analyzed via a chi-square test, or a Fisher’s exact test if the expected count was less than 5.Statistical analyses were performed with Statistical Analysis Software Version 9.3.

Results

A total of 302 patient records were evaluated.  The age range was 18-85 with an average age of 53.5.  Thirty eight percent of the patients were female and 41.8% of the patients had undergone HSCT.  A minority of the patients required mechanical ventilation either at the time of BAL or within 48 hours. One hundred seven of the 297 patients had a positive BAL culture for an overall BAL yield of 36%.  Of the 37 patients on antibiotics for less than 24 hours, including all 4 patients who were not on any antibiotics, twenty-one (56.8%) had a positive BAL culture compared with eighty-five of the 259 (32.8%) patients who had been on antibiotics longer than 24 hours at the time the BAL specimen was obtained and had a positive cultur.  Forty-eight patients were not receiving chemotherapy or immunosupressants, 15 (31.3%) of whom had a positive BAL yield.  One hundred twenty-six patients were on chemotherapy and 32 (25.4%) had a positive BAL culture.  Forty-one patients were not on chemotherapy but were on immunosupressants and 14 (34.1%) had a positive BAL yield.  Eighty patients were on both chemotherapy and immunosupressants and 46 (57.5%) had a positive BAL cultur. There were 64 patients with a normal WBC count and 30 (46.9%) had a positive BAL culture.  Patients with an abnormal WBC or frank neutropenia were less likely to have a positive BAL yield with 39.8% and 27.7% positive yield, respectively. Patients who were on antibiotics for at least 24 hours were significantly less likely to have a positive BAL yield. There was no significant difference in overall distribution of pathogen type.  There was a non-significant trend toward a lower incidence of fungi in those on antibiotics for at least 24 hours. 

Conclusion

It is common clinical practice to perform BAL in leukemic and bone marrow transplant patients with unexplained new lung infiltrates.  This study supports the practice of obtaining a BAL specimen within 24 hours of antimicrobial therapy in leukemic and HSCT patients with unexplained new lung infiltrates, a population that is universally on antimicrobials at the time of BAL.