Early Diagnosis of Aspergillosis in Patients at High Risk of Fungal Infection Caused by Treatment for Hematologic Cancer or Other Disease

Sponsor

St. Bartholomew's Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT00462657

Collaborator

(none)

200

Enrollment

Locations

100

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Studying ways to diagnose fungal infections early may help doctors plan the best treatment.

PURPOSE: This clinical trial is studying laboratory tests to see how well they find aspergillosis early in patients at high risk of fungal infection caused by treatment for hematologic cancer or other disease.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease Infection Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Genetic: polymerase chain reaction Other: bronchoalveolar lavage Other: immunoenzyme technique Other: laboratory biomarker analysis Procedure: bronchoscopy Procedure: management of therapy complications	N/A

Detailed Description

OBJECTIVES:

Primary

Determine the test characteristics of galactomannan (GM) ELISA using serum and bronchoalveolar lavage fluid (BALF) collected from patients at high risk of invasive fungal infection.
Determine the test characteristics of aspergillus PCR using blood and BALF samples collected from these patients.
Evaluate the role of noninvasive exhaled breath condensate (EBC) in detecting invasive aspergillosis (IA).
Determine whether repeated measures over time or a combination of markers improves the test characteristics.
Establish cutoff points for the diagnosis of IA.

Secondary

Determine the inflammatory marker and cytokine profile of EBC in fungal infection and after bone marrow transplantation as a marker of acute lung injury.
Assess the role of bronchoscopy with bronchoalveolar lavage in identifying the causal pathogen early in the disease course of febrile neutropenic patients.
Assess the role of GM ELISA in prognosis and response to treatment for IA.
Assess the role of aspergillus PCR in prognosis and response to treatment for IA.

OUTLINE: This is a prospective study.

Patients are assessed for early diagnosis of invasive aspergillosis (IA) using serum and bronchoalveolar lavage fluid (BALF) evaluated by ELISA for galactomannan (GM) antigen and real time PCR for fungal DNA. Serum samples are collected at baseline and periodically during study, beginning with the onset of neutropenia and continuing until resolution of fever or recovery of neutrophil count. BALF samples are collected in patients with abnormal chest radiology evaluated by bronchoscopy and bronchoalveolar lavage. BALF is analyzed for GM antigen, fungal DNA, inflammatory markers, and cytokines.

Patients are also assessed using exhaled breath condensate (EBC) evaluated by GM ELISA and real time PCR. EBC is collected at baseline and periodically during study to detect GM antigen or fungal DNA and to measure markers of pulmonary inflammation and oxidative stress (e.g., pH, hydrogen peroxide, and leukotriene B4).

PROJECTED ACCRUAL: A total of 200 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Primary Purpose:

Diagnostic

Official Title:

Early Diagnosis of Invasive Aspergillosis in a High Risk Group of Patients Using Serum and Bronchoalveolar Lavage Fluid Real Time PCR and Galactomannan ELISA

Study Start Date :

Jul 1, 2005

Outcome Measures

Primary Outcome Measures

Sensitivity and specificity of galactomannan (GM) ELISA and real time PCR in detecting invasive aspergillosis (IA) []
Diagnostic value of IA screening by GM ELISA and real time PCR, in terms of positive and negative predicative values []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

At high risk for developing invasive aspergillosis (IA) due to any of the following risk factors:
Diagnosis of acute myeloid leukemia, myelodysplastic syndromes, or acute lymphoblastic leukemia AND meets ≥ 1 of the following criteria:
Receiving intensive chemotherapy with expected duration of neutropenia (ANC < 500/mm³) of > 10 days
Receiving high-dose steroids
Concurrent treatment with allogeneic hematopoietic stem cell transplantation (HSCT)
Requirement for high-dose steroids for graft-versus-host disease after HSCT
History of probable or proven IA and receiving chemotherapy
No preexisting chest disease