galactomannan and Graft-vs-Host-Disease

Invasive aspergillosis (IA) is a serious hazard to haematological and critical care patients. Impactful risk factors for developing IA have been characterised; however, systematic analysis of baseline prognostic factors for treatment course of IA is missing. To understand prognostic variables, we analysed original articles identifying baseline factors that predict treatment outcome in patients with IA. PubMed database was searched for publications since database inception until May 2018. Inclusion criteria were published baseline prognostic factors present at the diagnosis of IA. In total, 58 studies from 267 centres reported 7320 patients with IA and 40 different predictors. Unfavourable predictors in medical history were kidney (7.4%, 10/136) and liver failure (3.7%, 5/136), ICU admission (3.7%, 5/136) and uncontrolled underlying disease (3.7%, 5/136). Regarding state of immunosuppression, negative outcome predictors were prolonged neutropenia (12.5%, 17/136), corticosteroid treatment (8.1%, 11/136) and graft-vs-host disease (3.7%, 5/136). On the pathogen side, relevant predictors were galactomannan positivity (8.1%, 11/136), Aspergillus terreus infection (2.2%, 3/136) and lack of amphotericin B susceptibility (1.5%, 2/136). IA-specific predictors were disseminated disease (5.1%, 7/136) and CNS involvement (2.9%, 4/136). Imaging results associated with negative outcome were multiple consolidations (2.9%, 4/136), bipulmonary lesions (2.2%, 3/136) and pleural effusion (2.2%, 3/136). At diagnosis of IA, most frequently identified predictors of outcome were neutropenia, corticosteroid use, elevated galactomannan, renal failure and disseminated disease. The predictors may be used to identify patients at high risk for treatment failure and to stratify neglected patient groups for clinical trials.

Topics: Adult; Antifungal Agents; Aspergillus; Galactose; Graft vs Host Disease; Humans; Immunosuppression Therapy; Invasive Pulmonary Aspergillosis; Mannans; Neutropenia; Prognosis; Retrospective Studies; Risk Factors; Treatment Failure; Treatment Outcome

Invasive aspergillosis (IA) is an important infectious complication in allogeneic stem cell transplant (SCT) recipients. Diagnosis of IA has been difficult and often delayed and treatment outcome has been poor, with mortality rates up to 80%. This review summarizes recent developments in this field. There are indications that the incidence of IA may be decreasing due to multiple factors including better understanding of pathogenesis of IA, earlier diagnosis, and various prophylactic and preventive strategies. Recently posaconazole has shown to be effective in reducing the risk of IA in patients treated for graft-versus-host disease (GVHD). Early use of high-resolution thoracic computed tomography assisted with complimentary methods including bronchoalveolar lavage and serum galactomannan determinations are useful in early diagnosis. Our treatment armamentarium against IA has broadened significantly during the last years and there are some indications of improved outcome more recently. On the other hand, increasing use of blood progenitor grafts instead of marrow with higher risk of chronic GVHD, increasing age of SCT recipients, and wide use of donor lymphocyte infusions for treatment of minimal residual disease or relapse may affect to the opposite direction. Despite some promises and improvements, IA will continue to remain a challenge in the upcoming years.

Topics: Antifungal Agents; Aspergillosis; Bronchoalveolar Lavage Fluid; Galactose; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Leukemia, Myeloid, Acute; Mannans; Polymerase Chain Reaction; Risk Factors; Transplantation, Homologous; Treatment Outcome

Topics: Antigens, Fungal; beta-Glucans; False Positive Reactions; Food; Galactose; Glucans; Glucocorticoids; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Invasive Fungal Infections; Kelp; Male; Mannans; Methylprednisolone; Middle Aged; Proteoglycans; Sezary Syndrome; Tomography, X-Ray Computed; Transplantation Conditioning

Topics: Adult; False Positive Reactions; Female; Food Additives; Food Analysis; Food Contamination; Galactose; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Mannans

PCR screening for circulating DNA, especially when combined with antigen testing, has shown promise for the definitive diagnosis of invasive aspergillosis. False positives for Aspergillus real-time PCR assays have been described in several reports, but no sources of fungal DNA contamination could be clearly identified. We report a false-positive case for both galactomannan (GM) antigenemia and Aspergillus PCR due to nutritional supplement intake in a bone marrow transplant recipient with digestive graft-versus-host disease. Our case report also suggests that fungal DNA can pass into the serum from the intestinal tract in the same way as fungal GM. Clinicians should be aware of this possibility, so that the administration of costly, unnecessary antifungal treatments with potential adverse side-effects can be avoided.

Topics: Adult; Aspergillosis; Aspergillus; Bone Marrow Transplantation; Dietary Supplements; DNA, Fungal; False Positive Reactions; Galactose; Graft vs Host Disease; Humans; Immunocompromised Host; Male; Mannans; Reverse Transcriptase Polymerase Chain Reaction

In this prospective study including 78 adult patients with haematological malignancy (90 episodes) we performed galactomannan (GM) (Platelia Aspergillus) screening twice weekly for the diagnosis of invasive aspergillosis. There were five proven and four probable invasive aspergillosis cases. The sensitivity, specificity and positive and negative predictive values were 100, 88, 47 and 100%, respectively. There were eight patients with false positive GM (10.2%). In six patients the false GM reactivity was due to the administration of piperacillin-tazobactam (P-T). A significant association was found between false positive GM (= or > 0.5) and the administration of P-T (p < 0.01). Two other patients with no invasive aspergillosis (2.5%) and false GM reactivity had graft versus host disease (GVHD) and one of them had also mucositis grade IV. The kinetic patterns of false positive GM due to P-T is discussed.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Artifacts; Aspergillosis; Biomarkers; Combined Modality Therapy; Enzyme-Linked Immunosorbent Assay; False Positive Reactions; Female; Fungemia; Galactose; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Mannans; Middle Aged; Mucositis; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity

We present a case of primary hepatic and possible splenic invasive aspergillosis (IA), which progressed under anti-CD20 B cell treatment for posttransplantation lymphoproliferative disease following allogeneic stem cell transplantation, to highlight the clinical value of a positive galactomannan-antigen test, an intestinal portal of entry of Aspergillus, and the detrimental effect of B lymphocyte depletion in IA.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Chemical and Drug Induced Liver Injury; Fatal Outcome; Female; Galactose; Graft vs Host Disease; Humans; Liver Diseases; Lymphoproliferative Disorders; Mannans; Middle Aged; Pyrimidines; Rituximab; Splenic Diseases; Stem Cell Transplantation; Transplantation, Homologous; Triazoles; Voriconazole

Topics: Adult; Aspergillosis; Aspergillus; Enzyme-Linked Immunosorbent Assay; False Positive Reactions; Female; Galactose; Gastrointestinal Diseases; Graft vs Host Disease; Humans; Mannans; Reproducibility of Results; Soybean Proteins

Topics: Adult; Antigens, Fungal; Aspergillosis; Aspergillus; Bone Marrow Transplantation; Chronic Disease; Enzyme-Linked Immunosorbent Assay; False Positive Reactions; Female; Galactose; Graft vs Host Disease; Humans; Mannans; Transplantation, Homologous