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.
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.
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Ramzi
R
Abboud
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Jesse
J
Keller
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Michael
M
Slade
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
John F
JF
DiPersio
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Peter
P
Westervelt
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Michael P
MP
Rettig
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Stephanie
S
Meier
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Todd A
TA
Fehniger
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Camille N
CN
Abboud
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Geoffrey L
GL
Uy
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Ravi
R
Vij
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, Missouri.
Kathryn M
KM
Trinkaus
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri.
Mark A
MA
Schroeder
BMT and Leukemia Program, Washington University School of Medicine, St Louis, Missouri. Electronic address: rromee@wustl.edu.
Rizwan
R
Romee
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods* / Q000401:mortality; D016019:Survival Analysis; D013577:Syndrome; D013601:T-Lymphocytes; D000075442:Transplantation, Haploidentical / Q000009:adverse effects* / Q000379:methods* / Q000401:mortality; D055815:Young Adult; D000093242:Interleukin-6 Inhibitors
D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C502936:tocilizumab
Cytokine-release syndrome (CRS); Haploidentical; Tocilizumab; Transplantation-related mortality (TRM)