Engraftment syndrome: double-edged sword of hematopoietic cell transplants

Abstract

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.

A Young Patient with Refractory Multiple Myeloma and Dialysis-Dependent Renal Failure has been Cured by Non-Cryopreserved Autologous Stem Cell Transplantation Followed by Live-Related Kidney Transplantation

“…It was first described by Lee et al in a retrospective analysis of 248 patients with cancer undergoing auto-HSCT [29,30]. ES has also been described after allogeneic HSCT, but it has been more frequently reported following auto-HSCT [28,31,32]. The risk factors of ES include: MM and lymphoma as the underlying illnesses, previously administered chemotherapy and radiotherapy, faster engraftment and infusion of higher number of stem cells [14,28].…”

“…The clinical manifestations of ES resemble those of acute GVHD and they include: fever, skin rash, hepatic and renal dysfunction, transient encephalopathy, capillary leak syndrome and death [28,29,31,33]. ES has to be differentiated from autologous GVHD, infections as well as drug toxicity and radiation induced tissue damage [31]. ES is typically self-limited and it usually responds to corticosteroids, supportive care and other immunosuppressive…”

“…The risk factors of ES include: MM and lymphoma as the underlying illnesses, previously administered chemotherapy and radiotherapy, faster engraftment and infusion of higher number of stem cells [14,28]. The clinical manifestations of ES resemble those of acute GVHD and they include: fever, skin rash, hepatic and renal dysfunction, transient encephalopathy, capillary leak syndrome and death [28,29,31,33]. ES has to be differentiated from autologous GVHD, infections as well as drug toxicity and radiation induced tissue damage [31].…”

“…agents although intensive care and mechanical ventilation may be required in severe forms [29,[31][32][33].…”

Non-Infectious Early Complications of Allogeneic Stem Cell Transplantations

“…58 Vascular leak, organ dysfunction and constitutional signs such as fever are secondary to activated leucocytes and pro-inflammatory cytokines during engraftment process. 59 It was reported that IL-1, TNFalpha, interferon gamma, IL-2 receptor-alpha and TNF-receptor levels increased in ES as in acute International Journal of Hematology and Oncology GVHD. 54 Soluble thrombomodulin and plasminogen activator type I, CRP increase and complement activation are changes detected in ES.…”