Treatment of severe steroid refractory acute graft-versus-host disease with infliximab, a chimeric human/mouse antiTNFalpha antibody.
Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Patients with severe aGVHD not responding to treatment with steroids have a poor prognosis. We treated four patients with severe aGVHD refractory to steroids with infliximab, a chimeric human/mouse antiTNFalpha antibody. Patients (CML 2, MM 1, AML 1) developed grade III-IV GVHD at a median of 34 days (range 15-76) after myeloablative PBSCT (two), donor lymphocyte infusion for relapsed CML (one) or non-myeloablative PBSCT (one), respectively. All patients had severe intestinal involvement in addition to skin and/or liver disease and had received treatment with high-dose steroids (four) for a median of 11 days (range 5-17) in addition to CsA (four) and MMF (three). Infliximab (10 mg/kg) was given once a week until clinical improvement. In three of four patients a complete resolution of diarrhea and significant improvement of skin and liver disease were observed. Two patients received one, one patient two and one patient three infliximab infusions. At present two patients are alive >200 days after therapy, one with limited cGVHD. Two patients died, one of progressive malignant disease without GVHD and one of refractory GVHD. Infliximab is apparently an active drug for the treatment of aGVHD.
Kobbe
G
G
Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine University Düsseldorf, Germany.
Schneider
P
P
Rohr
U
U
Fenk
R
R
Neumann
F
F
Aivado
M
M
Dietze
L
L
Kronenwett
R
R
Hünerlitürkoglu
A
A
Haas
R
R
D000208:Acute Disease; D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000473:pathology; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D000069285:Infliximab; D008297:Male; D051379:Mice; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D016879:Salvage Therapy; D013256:Steroids / Q000627:therapeutic use; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab