Engraftment syndrome in breast cancer patients after stem cell transplantation is associated with poor long-term survival

Summary:The engraftment syndrome (ES) is a phenomenon observed in some patients undergoing autologous hematopoietic stem cell transplant (AHSCT). ES is characterized by fever, rash, capillary leak, and pulmonary infiltrates occurring at the onset of engraftment. Prior studies have suggested that the administration of hematopoietic growth factors post-transplant results in the increased frequency of ES. However, the relative contribution of granulocyte colony-stimulating factor (G-CSF) vs granulocyte-macrophage colony-stimulating factor (GM-CSF) to the development of ES remains unknown. A total of 152 consecutive patients who were treated with high-dose chemotherapy and AHSCT supported by either G-CSF or GM-CSF were analyzed retrospectively. In all, 20 patients developed ES, an incidence of 13%. ES was seen more frequently in patients who received GM-CSF (GM-CSF 24% vs G-CSF 4%, p ¼ 0.0001). The highest incidence of ES was observed in breast cancer patients (42% of breast cancer patients; 70% of all ES cases). Comparison of the incidence of ES by the priming regimen used comprising either of the growth factors revealed no significant association (p ¼ 0.8224). This study demonstrates that the incidence of ES is higher using GM-CSF, particularly in patients with breast cancer. It suggests that it might be advantageous to administer only G-CSF in breast cancer patients undergoing AHSCT to reduce ES-related morbidity.

Section: Discussioncontrasting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Engraftment syndrome after autologous hematopoietic stem cell transplant supported by granulocyte-colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor (GM-CSF)

Akasheh

Eastwood

Vesole

2003

“…In a series of 85 patients who underwent autologous HSCT for breast cancer, an increased risk of relapse and an increased rate of late mortality were observed in women who developed ES. 11 The mechanism of this adverse prognostic effect of ES remains obscure.…”

Section: Autologous Stem Cell Transplantationmentioning

confidence: 99%

Engraftment syndrome following hematopoietic stem cell transplantation

Spitzer

2001

362

386

Summary:During neutrophil recovery following hematopoietic stem cell transplantation, a constellation of symptoms and signs including fever, erythrodermatous skin rash, and noncardiogenic pulmonary edema often occur. These clinical findings have usually been referred to as engraftment syndrome, or, reflecting the manifestations of increased capillary permeability, capillary leak syndrome. While described most often following autologous stem cell transplantation, a similar clinical syndrome has been observed followed allogeneic stem cell transplantation. Distinction from graft-versus-host disease in the allogeneic setting however, has been difficult. Recent experience with non-myeloablative conditioning for stem cell transplantation, however, reveals that an engraftment syndrome independent of GVHD may occur. In some cases, this engraftment syndrome may be a manifestation of a host-versus-graft reaction (graft rejection). While cellular and cytokine interactions are believed to be responsible for these clinical findings, a distinct effector cell population and cytokine profile have not been defined. Engraftment syndromes are likely associated with an increased transplant-related mortality, mostly from pulmonary and associated multiorgan failure. Corticosteroid therapy is often dramatically effective for engraftment syndrome, particularly for the treatment of the pulmonary manifestations. A proposal for a more uniform definition of engraftment syndrome has been developed in order to allow for a reproducible method of reporting of this complication and for evaluating prophylactic and therapeutic strategies. Bone Marrow Transplantation (2001) 27, 893-898.

“…There are also conflicting data regarding an association between ES, NRM and survival. 1,2,[10][11][12][13][14][15] Some of these discordances likely reflect different definitions of ES.…”

Section: Introductionmentioning

confidence: 99%

Engraftment syndrome: double-edged sword of hematopoietic cell transplants

Spitzer

2015

116

128

Engraftment syndrome (ES) after hematopoietic cell transplantation (HCT) is increasingly diagnosed. Common features include fever, pulmonary vascular leak, rash and organ dysfunction. Different diagnostic criteria likely account for the wide (7-90%) range of reported incidences. ES typically occurs within 4 days of granulocyte recovery although a recently described seemingly similar syndrome occurs 41 week before granulocyte recovery after umbilical cord blood cell transplants. Although the clinical manifestations of ES may be identical to those of acute GVHD, ES also has been well described in patients without acute GVHD. The data are conflicting as to whether ES is associated with a higher nonrelapse mortality and worse survival after HCT. The pathophysiology of ES is unclear, but endothelial injury and activated granulocytes in the setting of proinflammatory cytokines may be important. ES typically is self-limited, but, like acute GVHD, responds to corticosteroids. Because ES and acute GVHD may have overlapping features and response to therapy, these disease processes may often not be distinct events. Moreover, features of ES may overlap with those of drug-and radiation-induced toxicities and infection. Further research to better characterize the clinical spectrum and etiology of ES and to determine its relationship to GVHD is needed.