Patients with hematologic malignancies have a high rate of opportunistic infections (OIs) with pathogens that could lead to the formation of brain abscesses. Nocardia, toxoplasmosis, Aspergillus, zygomycetes and Fusarium are a few of these organisms, which may be increasing in prevalence. Several immunologic defects such as severe neutropenia (absolute neutrophil count < 500), impaired B-cell immunity, hypogammaglobulinemia, and defective T-cell immunity are related with increased risk of OIs. Recipients of hematopoietic stem cell transplantation (HSCT) are similarly at an increased risk of these OIs due to prolonged neutropenia and defective T-cell–mediated immunity.
Design and Methods
A retrospective case series analysis at Moffitt Cancer Center, a tertiary cancer hospital, screened for patients with hematologic malignancies and microbiological proven diagnosis of opportunistic brain abscess (OBA) from January 1998 to January 2010. The OBAs were diagnosed via positive cultures from cerebrospinal fluid, brain tissue, or bronchoalveolar lavage for one of the following microorganisms: Nocardia species, Toxoplasmosa species, Aspergillus species, zygomycetes, or Fusarium species; 5 of the 13 cases involved recipients after allogeneic HSCT. A literature review of the most common pathogens related to OBAs in hematologic patients from PubMed between 1998 and 2011 is also included.
The OBAs documented by culture included Nocardia (5/13, 38%), zygomycetes (3/13, 23%), toxoplasmosis (2/13, 15%), Aspergillus (2/13, 15%), and a single case of disseminated Fusarium (1/13, 8%). The underlying hematologic malignancies were as follows: lymphoma (4/13, 2 cases involved Hodgkin lymphoma and 2 cases involved non-Hodgkin lymphoma), chronic myeloid leukemia (3/13), acute lymphoblastic leukemia (ALL) (3/13), acute myelogenous leukemia (AML) (1/13), multiple myeloma (1/13), and myelodysplastic syndrome (1/13). The age range at diagnosis was 26 to 76 years, with a median age of 51 years at the time of diagnosis with OBA. The male-to-female ratio was 3.3:1 (10 males, 3 females). The most common predisposing factors were severe neutropenia for 7 to 15 days within the month before the diagnosis (6/13, 46%), chronic graft-versus-host disease (GVHD) after allogeneic HSCT (5/13, 38%), lymphoma (4/13, 30%), chronic lymphocytic leukemia, and ALL (3/13, 23%). Of the 13 patients, 7 (54%) had severe neutropenia (absolute neutrophil count < 500 cell/µL) within the month before OBA diagnosis, but only 1 had a prolonged neutropenia for more than 6 months. None of the patients with Nocardia brain abscesses were neutropenic during the year before the diagnosis. The most common presenting symptoms were focal neurologic deficits (7/13, 54%), headaches (5/13, 38%), and altered mental status (5/13, 38%).
An OBA should be highly suspected in patients with lymphoma, chronic lymphocytic leukemia, ALL, or chronic GVHD presenting with headache and focal neurologic deficits. The most important risk factor for OBA in allogeneic transplant after engraftment is the development of chronic GVHD and effects of its subsequent immunosuppressive treatment. Chronic GVHD is associated with persistently depressed T-cell and humoral immunity. Perhaps Trimethoprim- and sulfamethoxazole-based prophylaxis should be considered for the prevention of OBA infections in HSCT with chronic GVHD complications. Early OBA diagnosis, surgical intervention if indicated, and culture-directed treatment is vital for decreased morbidity and mortality.