Cytokine release syndrome after HLA-haploidentical stem cell transplantation with posttransplant cyclophosphamide

Abstract

 HLA-haploidentical stem cell transplantation using post-transplant cyclophosphamide (PTCy-haploSCT) is increasingly being performed in clinical practice. Although PTCy-haploSCT is associated with a low risk of severe graft-versus-host disease and non-relapse mortality, cytokine release syndrome (CRS) is a major complication after PTCy-haploSCT. CRS, caused by hypercytokinemia, presents with diverse symptoms, including fever, hypotension, and respiratory failure. Patients may develop a variety of symptoms; however, the major clinical manifestation of CRS is high-grade fever early after stem cell infusion. Although CRS is mild in most patients and resolves rapidly after PTCy administration, some patients may develop a severe form of this condition. Tocilizumab administration is recommended in patients with severe CRS; however, corticosteroids serve as first-line therapy because tocilizumab is not approved for PTCy-haploSCT-induced CRS in Japan. Prophylactic corticosteroid administration before PTCy should be avoided because corticosteroids inhibit proliferation of alloreactive T cells and can theoretically reduce the effectiveness of PTCy. Severe CRS is known to be associated with poor prognosis; however, the effects of mild CRS on transplantation outcomes remain unclear. Further investigations are warranted to confirm whether an acceptable level of CRS is associated with antitumor effects.