Addition of infliximab to standard acute graft-versus-host disease prophylaxis following allogeneic peripheral blood cell transplantation.
Infliximab, a chimeric monoclonal antibody (mAb) against tumor necrosis factor (TNF)-alpha, has shown activity against steroid refractory acute graft-versus-host disease (aGVHD). We conducted a prospective trial of infliximab for the prophylaxis of aGVHD. Patients older than 20 years undergoing myeloablative allogeneic stem cell transplantation (SCT) for hematologic malignancies were eligible. GVHD prophylaxis consisted of infliximab given 1 day prior to conditioning and then on days 0, +7, +14, +28, and +42, together with standard cyclosporine (CSA) and methotrexate (MTX). Nineteen patients with a median age of 53 years were enrolled. All patients received peripheral blood allografts from matched sibling (n = 14) or unrelated donors (n = 5). Results were compared with a matched historic control group (n = 30) treated contemporaneously at our institution. The cumulative incidences of grades II-IV aGVHD in the infliximab and control groups were 36.8% and 36.6%, respectively (P = .77). Rates of chronic GVHD were 78% and 61%, respectively (P = .22). Significantly more bacterial and invasive fungal infections were observed in the infliximab group (P = .01 and P = .02, respectively). Kaplan-Meier estimates of 2-year overall survival (OS) and progression free survival (PFS) for patients receiving infliximab were 42% and 36%, respectively. The corresponding numbers for patients in the control group were 46% and 43%, respectively. The addition of infliximab to standard GVHD prophylaxis did not lower the risk of GVHD and was associated with an increased risk of bacterial and invasive fungal infections.
Division of Hematology & Oncology, Arthur G. James Cancer Hospital, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Mehdi
M
Hamadani
Craig C
CC
Hofmeister
Buffy
B
Jansak
Gary
G
Phillips
Patrick
P
Elder
William
W
Blum
Sam
S
Penza
Thomas S
TS
Lin
Rebecca
R
Klisovic
Guido
G
Marcucci
Sherif S
SS
Farag
Steven M
SM
Devine
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D001424:Bacterial Infections / Q000209:etiology; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D000069285:Infliximab; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab