Changing landscape of invasive aspergillosis in allogeneic stem cell transplant recipients

Abstract

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.

Bone Marrow Transplantation Combined with Mesenchymal Stem Cells Induces Immune Tolerance without Cytotoxic Conditioning

“…However, the cytotoxic conditioning, which has shown engraftment-enhancing effects [31,32], increases the risks of infection [33,34], tumorigenesis [35][36][37], multiple organ failure and other adverse effects [38,39] in recipients. Therefore, clinical application of mixed chimerism prepared by current protocol is hindered by advert effects of recipient conditioning.…”

CCR7 alters hematopoietic potential

“…Given that anti-IA immunity is predominantly mediated by cells of myeloid origin (although lymphoid-derived cells have been also recognized as effector cells), many attempts have been made to either engineer the stem cell graft to impact the disease or to accelerate myeloid cell differentiation and enhance effector cell production after allogeneic HSCT. 2 The role of chemokines in regulating many fundamental processes of hematopoietic cells-including survival, proliferation, differentiation, and migration-is well recognized. 3 Chemokine receptors are expressed on a large number of primitive hematopoietic cells as well as differentiated and specialized cells such as T cells.…”

Epidemiology of Invasive Pulmonary Aspergillosis

“…The reason for this increase was likely due to the expanding population of immunocompromised patients, who were surviving longer because of improved treatment of their underlying condition, changes in transplantation practices, and institution of effective prophylaxis for common infections, such as those caused by Candida species and cytomegalovirus (CMV) [9,10]. These patients were often profoundly immunosuppressed, increasing the risk for invasive mould infections.…”