Treatment of steroid-resistant graft-versus-host disease after allogeneic bone marrow transplantation with anti-CD3/TCR monoclonal antibodies.
Acute graft-versus host disease (GVHD), one of the major complications of allogeneic bone marrow transplantation (BMT), occurs in 30-50% of all patients transplanted from HLA-identical sibling donors and in 50-80% of all patients transplanted from an unrelated or HLA-mismatched family donor, despite GVHD prophylaxis with methotrexate and cyclosporin. We report our experience with OKT3/BMA031 treatment in 14 patients with severe steroid-resistant GVHD following allogeneic BMT. Three of 5 patients treated in the early post-transplant period with OKT3 remitted and 2 of 3 became long-term survivors. Two patients treated for extensive chronic GVHD showed only minor responses. Five of 7 patients treated with BMA031 showed a partial remission; no complete remission was seen after treatment with this antibody. Shortly after the introduction of OKT3 or BMA031 therapy a rapid decline of the lymphocyte count, especially the CD3+ subset, was observed coinciding with a relative increase of CD56+ lymphocytes and of gamma/delta TCR+ T cells. Increasing numbers of CD3+ lymphocytes preceded recurrence of acute GVHD in three patients. In contrast, persisting CD3-lymphocytopenia was associated with complete clearance of acute GVHD. The incidence of infectious complications following OKT3 or BMA031 therapy was high (42%). Thus, to improve treatment results of severe acute GVHD, prophylactic or pre-emptive strategies are required to reduce the rate of fatal viral and fungal infections.
Hebart
H
H
Medizinische Universitätsklinik Tübingen, Abteilung II, Germany.
Ehninger
G
G
Schmidt
H
H
Berner
B
B
Reuss-Borst
M
M
Waller
H D
HD
Müller
C A
CA
Einsele
H
H
D000208:Acute Disease; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D006680:HLA Antigens / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007116:Immunization, Passive; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007239:Infections / Q000209:etiology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D011239:Prednisolone / Q000627:therapeutic use; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016879:Salvage Therapy; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D011948:Receptors, Antigen, T-Cell; D011239:Prednisolone