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 b… Show more
“…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.…”
The prognostic significance of eosinophilia after allogeneic hematopoietic SCT (HSCT) and the relationship between eosinophilia and acute GVHD are not well studied. We retrospectively analyzed 201 adult patients who underwent their first allogeneic HSCT. Seventy-three (36%) patients developed eosinophilia within the first 100 days after HSCT. Eosinophilia was observed more frequently among those patients with acute GVHD than those without it (48 vs 25%, P ¼ 0.009). However, it was associated with milder acute GVHD and lower incidence of gut and liver acute GVHD. Among patients with acute GVHD, the 3-year OS for patients with and without eosinophilia was 63.4 and 47.2% (P ¼ 0.02), respectively, and 3-year nonrelapse mortality (NRM) was 20.2 and 37.5% (P ¼ 0.01), respectively. Multivariate analysis confirmed that eosinophilia was associated with a better OS (P ¼ 0.03) and lower NRM (P ¼ 0.046) in patients with acute GVHD, whereas it was not associated with a higher relapse rate (P ¼ 0.45). In contrast, eosinophilia was not associated with outcomes in those patients without acute GVHD. In conclusion, eosinophilia was associated with milder acute GVHD and better prognosis among patients with acute GVHD. The pathophysiology behind eosinophilia after allogeneic HSCT remains to be investigated.
“…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.…”
The prognostic significance of eosinophilia after allogeneic hematopoietic SCT (HSCT) and the relationship between eosinophilia and acute GVHD are not well studied. We retrospectively analyzed 201 adult patients who underwent their first allogeneic HSCT. Seventy-three (36%) patients developed eosinophilia within the first 100 days after HSCT. Eosinophilia was observed more frequently among those patients with acute GVHD than those without it (48 vs 25%, P ¼ 0.009). However, it was associated with milder acute GVHD and lower incidence of gut and liver acute GVHD. Among patients with acute GVHD, the 3-year OS for patients with and without eosinophilia was 63.4 and 47.2% (P ¼ 0.02), respectively, and 3-year nonrelapse mortality (NRM) was 20.2 and 37.5% (P ¼ 0.01), respectively. Multivariate analysis confirmed that eosinophilia was associated with a better OS (P ¼ 0.03) and lower NRM (P ¼ 0.046) in patients with acute GVHD, whereas it was not associated with a higher relapse rate (P ¼ 0.45). In contrast, eosinophilia was not associated with outcomes in those patients without acute GVHD. In conclusion, eosinophilia was associated with milder acute GVHD and better prognosis among patients with acute GVHD. The pathophysiology behind eosinophilia after allogeneic HSCT remains to be investigated.
“…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).…”
“…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.…”
Section: Soluble Factors and Their Targetsmentioning
Summary:Hematopoietic stem cell transplantation (HSCT) is the definitive cure for many malignant and nonmalignant diseases. However, delays in immune reconstitution (IR) following HSCT significantly limit the success of transplantation and increase the risk for infection and disease relapse in the transplant recipient. Therefore, ways to measure and to manipulate immune recovery following HSCT are emerging and their success depends directly upon an enhanced understanding for the underlying mechanisms responsible for reconstituted immunity and hematopoiesis. Recent discoveries in the activation, function, and regulation of dendritic cell (DC), natural killer (NK) cell, and T-lymphocyte subtypes have been critical in developing immunotherapies used to prevent graft-versushost disease and to enhance graft-versus-leukemia. For example, regulatory T cells that induce tolerance and NK receptor-tumor ligand disparities that result in tumor lysis are being used to minimize GVHD and tumor burden, respectively. Furthermore, expansion and modulation of immune effector cells are being used to augment hematopoietic and immune recovery and to decrease transplantrelated toxicity in the transplant recipient. Specifically, DC expansion and incorporation into antitumor and antimicrobial vaccines is fast approaching application into clinical trials. This paper will review our current understanding for IR following HSCT and the novel ways in which to restore immune function and decrease transplantrelated toxicity in the transplant recipient. Bone Marrow Transplantation (2005) 35, 835-857.
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