ABSTRACT
OBJECTIVES: To evaluate risk factors, diagnostic procedures, and treatment outcomes of invasive aspergillosis (IA) in patients with hematological malignancies. METHODS: A retrospective analysis of data from proven/probable IA cases that occurred from 2005 to 2009 at 10 hematology centers was performed. RESULTS: We identified 176 IA cases that mainly occurred in patients with acute leukemias (58.5%), mostly those on induction/re-induction treatments (39.8%). Prolonged neutropenia was the most frequent risk factor for IA (61.4%). The lungs were the most frequently affected site (93.8%) and computed tomography detected abnormalities in all episodes; however, only 53.7% of patients had findings suggestive of IA. Galactomannan (GM) detection in serum or bronchoalveolar lavage fluid (positive in 79.1% and 78.8% of episodes, respectively) played a crucial role in IA diagnosis. Neutrophil count and antifungal prophylaxis did not influence the GM positivity rate, but empirical therapy decreased this rate (in serum). Of the IA cases, 53.2% responded to initial antifungal therapy. The combination of voriconazole and echinocandin, even as initial or salvage therapy, did not perform better than voriconazole monotherapy (p=0.924 for initial therapy and p=0.205 for salvage therapy). Neutrophil recovery had a significant role in the response to initial (but not salvage) antifungal therapy. CONCLUSIONS: Our retrospective analysis identified key diagnostic and treatment characteristics, and this understanding could improve the management of hematological malignancy patients with IA.
Subject(s)
Antifungal Agents/therapeutic use , Aspergillosis/epidemiology , Leukemia/epidemiology , Lung Diseases, Fungal/epidemiology , Acute Disease , Adolescent , Adult , Aged , Antifungal Agents/immunology , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Bronchoalveolar Lavage Fluid , Child , Child, Preschool , Czech Republic/epidemiology , Databases, Factual , Echinocandins/therapeutic use , Female , Galactose/analogs & derivatives , Humans , Leukemia/diagnosis , Leukemia/drug therapy , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/drug therapy , Male , Mannans/blood , Middle Aged , Neutrophils/cytology , Pyrimidines/therapeutic use , Retrospective Studies , Slovakia/epidemiology , Triazoles/therapeutic use , Voriconazole , Young AdultABSTRACT
Biallelic germline mutations of Constitutional mismatch repair-deficiency syndrome (CMMR-D) genes, MLH1, MSH2, MSH6, and PMS2 are characterized by increased risk of childhood malignancy. We report a case with CMMR-D caused by novel homozygous MSH6 mutations leading to gliomatosis cerebri and T-ALL in an 11-year-old female and glioblastoma multiforme in her 10-year-old brother, both with rapid progression of the diseases. A literature review on brain tumors in CMMR-D families shows that they are treatment-resistant and lead to early death. Identification of patients with CMMR-D is critical, and specific cancer screening programs with early surgery are recommended.
