TY - JOUR
T1 - Severe Cytokine-Release Syndrome after T Cell–Replete Peripheral Blood Haploidentical Donor Transplantation Is Associated with Poor Survival and Anti–IL-6 Therapy Is Safe and Well Tolerated
AU - Abboud, Ramzi
AU - Keller, Jesse
AU - Slade, Michael
AU - DiPersio, John F.
AU - Westervelt, Peter
AU - Rettig, Michael P.
AU - Meier, Stephanie
AU - Fehniger, Todd A.
AU - Abboud, Camille N.
AU - Uy, Geoffrey L.
AU - Vij, Ravi
AU - Trinkaus, Kathryn M.
AU - Schroeder, Mark A.
AU - Romee, Rizwan
N1 - Publisher Copyright:
© 2016 The American Society for Blood and Marrow Transplantation
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Use of high-dose post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis has expanded the use of unmanipulated haploidentical hematopoietic cell transplantation. The immediate post-transplantation course in T cell–replete peripheral blood haploidentical hematopoietic cell transplantation (haplo-HCT) is often complicated by symptoms resembling cytokine-release syndrome (CRS), previously described in recipients of targeted cellular therapeutics. However, we know little about the incidence and impact of CRS on outcomes in these patients. To understand this syndrome in haplo-HCT patients, we reviewed data from 75 consecutive patients who received granulocyte colony–stimulating factor–mobilized T cell–replete peripheral blood haplo-HCT at a single center. Using CRS criteria described in recipients of chimeric antigen receptor T cell therapies, we found 65 of 75 (87%) met criteria for CRS, although most cases were only mild (grades 1 or 2). However, 9 patients (12%) experienced severe (grades 3 or 4) CRS. Median survival was 2.6 months (95% confidence interval [CI], 43 to 5.8) in patients with severe CRS, compared with 13.1 months (95% CI, 8.1 to not reached) in patients with mild CRS. Transplantation-related mortality was worse in the severe CRS cohort with a hazard ratio of 4.59 (95% CI, 1.43 to 14.67) compared with that in the mild CRS cohort. Severe CRS patients had a significant delay in median time for neutrophil engraftment. Serum IL-6 levels were measured in 10 haplo-HCT patients and were elevated in the early post-transplantation setting. Seven patients with CRS were treated with tocilizumab, resulting in a complete resolution of their CRS symptoms. Severe CRS represents a potential complication of peripheral blood haplo-HCT and is associated with worse outcomes. Anti–IL-6 receptor therapy is associated with rapid resolution of the CRS symptoms.
AB - Use of high-dose post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis has expanded the use of unmanipulated haploidentical hematopoietic cell transplantation. The immediate post-transplantation course in T cell–replete peripheral blood haploidentical hematopoietic cell transplantation (haplo-HCT) is often complicated by symptoms resembling cytokine-release syndrome (CRS), previously described in recipients of targeted cellular therapeutics. However, we know little about the incidence and impact of CRS on outcomes in these patients. To understand this syndrome in haplo-HCT patients, we reviewed data from 75 consecutive patients who received granulocyte colony–stimulating factor–mobilized T cell–replete peripheral blood haplo-HCT at a single center. Using CRS criteria described in recipients of chimeric antigen receptor T cell therapies, we found 65 of 75 (87%) met criteria for CRS, although most cases were only mild (grades 1 or 2). However, 9 patients (12%) experienced severe (grades 3 or 4) CRS. Median survival was 2.6 months (95% confidence interval [CI], 43 to 5.8) in patients with severe CRS, compared with 13.1 months (95% CI, 8.1 to not reached) in patients with mild CRS. Transplantation-related mortality was worse in the severe CRS cohort with a hazard ratio of 4.59 (95% CI, 1.43 to 14.67) compared with that in the mild CRS cohort. Severe CRS patients had a significant delay in median time for neutrophil engraftment. Serum IL-6 levels were measured in 10 haplo-HCT patients and were elevated in the early post-transplantation setting. Seven patients with CRS were treated with tocilizumab, resulting in a complete resolution of their CRS symptoms. Severe CRS represents a potential complication of peripheral blood haplo-HCT and is associated with worse outcomes. Anti–IL-6 receptor therapy is associated with rapid resolution of the CRS symptoms.
KW - Cytokine-release syndrome (CRS)
KW - Haploidentical
KW - Tocilizumab
KW - Transplantation-related mortality (TRM)
UR - http://www.scopus.com/inward/record.url?scp=84992055543&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2016.06.010
DO - 10.1016/j.bbmt.2016.06.010
M3 - Article
C2 - 27318038
AN - SCOPUS:84992055543
SN - 1083-8791
VL - 22
SP - 1851
EP - 1860
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 10
ER -