Monoclonal Anti-Tumor Necrosis Factor-Alpha Antibody for the Treatment of Severe Acute Graft-versus-Host Disease

2015 ◽  
pp. 102-106
Author(s):  
P. Herv� ◽  
J. Wijdenes ◽  
E. Racadot ◽  
P. Tiberghien ◽  
E. Plouvier ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Graft Versus Host Disease ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Host Disease ◽  
Graft Versus Host ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Acute Graft

scholarly journals Phase I-II trial of a monoclonal anti-tumor necrosis factor alpha antibody for the treatment of refractory severe acute graft-versus-host disease

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3362-3368 ◽  
Author(s):  
P Herve ◽  
M Flesch ◽  
P Tiberghien ◽  
J Wijdenes ◽  
E Racadot ◽  
...  
Keyword(s):  
Pilot Study ◽  
Tumor Necrosis Factor ◽  
Partial Response ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Graft Versus Host ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Acute Graft

Abstract In a multicenter pilot study, 19 patients with severe acute graft- versus-host disease (aGVHD) refractory to conventional therapy and serotherapy with a monoclonal anti-interleukin-2 receptor antibody were treated by in vivo infusion of a monoclonal anti-tumor necrosis factor alpha (TNF alpha) antibody (B-C7). Ten patients were grafted from a genotypically identical sibling, five from an HLA-mismatched family member, and four from an HLA-matched unrelated donor. Before B-C7 treatment, 15 patients had grade IV and four had grade III GVHD. In all cases, patients received cyclosporine/methotrexate as aGVHD prophylaxis. Patients were administered increasing doses of antibody (from 0.1 to 0.4 mg/kg). The antibody was infused in bolus daily for 4 days and then every other day twice (6 doses). No side effects were observed during treatment regardless of the dose level used. Changes in peripheral blood cell counts occurred in 8 of the 19 patients and appeared to be unrelated to B-C7. No truly complete response was observed; eight patients achieved a very good partial response (42.6%) and six a partial response (31.5%). The treatment was ineffective in five patients (26.4%). When present, the response occurred early (less than 3 days). In the 14 responding patients, gut lesions responded best (100%), followed by skin (85%) and liver (35.7%) lesions. In 9 of 11 evaluable patients (81%), GVHD recurred when treatment was discontinued in a median delay of 3 days (range, 2 to 120 days). All except one died from aGVHD. Two patients did not experience GVHD recurrence and are still alive 13 and 18 months post-bone marrow transplantation. This pilot study shows that a monoclonal anti-TNF alpha antibody may be of benefit to some patients with severe refractory aGVHD, but is ineffective to prevent GVHD recurrence in the majority of cases.

scholarly journals Phase I-II trial of a monoclonal anti-tumor necrosis factor alpha antibody for the treatment of refractory severe acute graft-versus-host disease

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3362-3368 ◽  
Author(s):  
P Herve ◽  
M Flesch ◽  
P Tiberghien ◽  
J Wijdenes ◽  
E Racadot ◽  
...  
Keyword(s):  
Pilot Study ◽  
Tumor Necrosis Factor ◽  
Partial Response ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Graft Versus Host ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Acute Graft

In a multicenter pilot study, 19 patients with severe acute graft- versus-host disease (aGVHD) refractory to conventional therapy and serotherapy with a monoclonal anti-interleukin-2 receptor antibody were treated by in vivo infusion of a monoclonal anti-tumor necrosis factor alpha (TNF alpha) antibody (B-C7). Ten patients were grafted from a genotypically identical sibling, five from an HLA-mismatched family member, and four from an HLA-matched unrelated donor. Before B-C7 treatment, 15 patients had grade IV and four had grade III GVHD. In all cases, patients received cyclosporine/methotrexate as aGVHD prophylaxis. Patients were administered increasing doses of antibody (from 0.1 to 0.4 mg/kg). The antibody was infused in bolus daily for 4 days and then every other day twice (6 doses). No side effects were observed during treatment regardless of the dose level used. Changes in peripheral blood cell counts occurred in 8 of the 19 patients and appeared to be unrelated to B-C7. No truly complete response was observed; eight patients achieved a very good partial response (42.6%) and six a partial response (31.5%). The treatment was ineffective in five patients (26.4%). When present, the response occurred early (less than 3 days). In the 14 responding patients, gut lesions responded best (100%), followed by skin (85%) and liver (35.7%) lesions. In 9 of 11 evaluable patients (81%), GVHD recurred when treatment was discontinued in a median delay of 3 days (range, 2 to 120 days). All except one died from aGVHD. Two patients did not experience GVHD recurrence and are still alive 13 and 18 months post-bone marrow transplantation. This pilot study shows that a monoclonal anti-TNF alpha antibody may be of benefit to some patients with severe refractory aGVHD, but is ineffective to prevent GVHD recurrence in the majority of cases.

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