Acute lung injury after allogeneic stem cell transplantation: is the lung a target of acute graft-versus-host disease?

Abstract

Summary:Allogeneic hematopoietic stem cell transplantation (SCT) is an important therapeutic option for a number of malignant and nonmalignant conditions but the broader application of this treatment strategy is limited by several side effects. In particular, diffuse lung injury is a major complication of SCT that responds poorly to standard therapeutic approaches and significantly contributes to transplant-related morbidity and mortality. Historically, approximately 50% of all pneumonias seen after SCT have been secondary to infection, but the judicious use of broad-spectrum antimicrobial prophylaxis in recent years has tipped the balance of pulmonary complications from infectious to noninfectious causes. This mini review will discuss the definition, risk factors and pathogeneses of noninfectious lung injury that occurs early after allogeneic SCT.

Eosinophilia predicts better overall survival after acute graft-versus-host-disease

“…34,35 Furthermore, patients who need corticosteroids after transplantation generally have a poor prognosis. [36][37][38] Accordingly, milder acute GVHD and better outcomes associated with eosinophilia may be due to the lower proportion of patients with eosinophilia who needed corticosteroids after transplantation compared with those without eosinophilia. To clarify this point, we analyzed separately the results among those patients who had corticosteroid therapy and those who did not.…”

Incidence and outcome of idiopathic pneumonia syndrome in pediatric stem cell transplant recipients

“…6,21 Murine data suggest that the pathogenesis of acute lung injury following GVHD may be the result of two pathways of immune-mediated injury following allogeneic SCT, a T-cell axis and an inflammatory cytokine axis. [22][23][24][25][26] In brief, the SCT conditioning process causes the release of tumor necrosis factor (TNF)a and interleukin (IL)-1 that increases the ability of host antigen-presenting cells to present alloantigens to mature donor T cells, thus upregulating chemokine expression in the lung. Donor T cells are activated and secrete interferong (which primes donor macrophages and monocytes) and IL-2 (which facilitates T-cell activation and generation of lymphocyte effectors, such as Th-1).…”

Immune restoration following hematopoietic stem cell transplantation: an evolving target

“…255 These same migratory factors and pathways are also used by deleterious alloimmune immune cells to localize in tissues such as the lung, where they cause direct cytotoxicity and endorgan damage. 256 Chemokines are chemotactic cytokine-like proteins that influence cell migration and response. [257][258][259] In addition to their migratory roles in inflammation, 260 chemokines have important roles in stem cell mobilization 261,262 and migration, 263 GVHD, 264 and cancer metastases.…”