TY - JOUR
T1 - Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease
AU - Yalniz, Fevzi F.
AU - Hefazi, Mehrdad
AU - McCullough, Kristen
AU - Litzow, Mark R.
AU - Hogan, William J.
AU - Wolf, Robert
AU - Alkhateeb, Hassan
AU - Kansagra, Ankit
AU - Damlaj, Moussab
AU - Patnaik, Mrinal M.
N1 - Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation
PY - 2017/9
Y1 - 2017/9
N2 - Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first-line treatment; however, less than one-half of patients achieve durable remission. Studies suggest that TNF-α, a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-α therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD. Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses (range, 1 to 6) on a weekly basis. The overall response rates were 40% (17% complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14% PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had infectious complications within 12 weeks of initiation of infliximab. These infections included 40 bacterial infections, 6 invasive fungal infections, and 5 viral reactivations. Twelve patients (34%) died secondary to infections. Overall survival at 12 weeks and 6 months from the start of infliximab therapy was 37% (13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to complications from GVHD and infections. In conclusion; the use of infliximab therapy in patients with SR-aGVHD is associated with a modest poorly sustained response along with a heightened risk of severe infections. Future studies with more effective and less toxic therapies are needed for these patients.
AB - Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first-line treatment; however, less than one-half of patients achieve durable remission. Studies suggest that TNF-α, a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-α therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD. Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses (range, 1 to 6) on a weekly basis. The overall response rates were 40% (17% complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14% PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had infectious complications within 12 weeks of initiation of infliximab. These infections included 40 bacterial infections, 6 invasive fungal infections, and 5 viral reactivations. Twelve patients (34%) died secondary to infections. Overall survival at 12 weeks and 6 months from the start of infliximab therapy was 37% (13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to complications from GVHD and infections. In conclusion; the use of infliximab therapy in patients with SR-aGVHD is associated with a modest poorly sustained response along with a heightened risk of severe infections. Future studies with more effective and less toxic therapies are needed for these patients.
KW - Acute graft-versus-host disease
KW - Allogeneic hematopoietic cell transplantation
KW - Tumor necrosis factor alpha blockade
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U2 - 10.1016/j.bbmt.2017.05.001
DO - 10.1016/j.bbmt.2017.05.001
M3 - Article
C2 - 28495641
AN - SCOPUS:85020390104
SN - 1083-8791
VL - 23
SP - 1478
EP - 1484
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -