Engraftment syndrome and associated cytokine storm and capillary leak syndrome

Abstract

While engraftment is the desired end point of hematopoietic stem cell transplantation (HSCT), the phase of neutrophil recovery can be complicated by two acute entities termed engraftment syndrome (ES) and capillary leak syndrome (CLS). Both ES and CLS result from the release of pro-inflammatory cytokines (e.g., IL-1, TNFα, and IFNγ) from donor cells in response to the recipient’s (or host’s) tissues. ES and CLS can be seen in both autologous and allogeneic HSCT settings. The incidence of ES has been reported to be 7-59% of autologous and 6-82% of allogeneic HSCTs. CLS is much more common than ES and is seen in myeloablative allogeneic HSCT. The clinical manifestations of ES range from mild, self-limited erythroderma, and high fevers to a more severe (and sometimes life-threatening) entity of acute weight gain, pulmonary edema, and hepatic and renal dysfunction with or without encephalopathy. CLS is characterized by weight gain, generalized edema, hypotension, prerenal failure, ascites, intravascular depletion, and pericardial and/or pleural effusions. CLS typically first manifests 1-3 days prior to neutrophil recovery as measured by a detectable ANC in the blood, whereas ES typically occurs shortly after the onset of neutrophil recovery. ES is treated with a short course (usually <7 days) of IV corticosteroids and supportive care including close management of fluid balance and use of diuretics. In contrast, CLS is managed with the aforementioned supportive care but not with corticosteroids. Early recognition and institution of careful fluid management is key to achieving a positive outcome from ES and CLS.