ABSTRACT
BACKGROUND: Polyneuropathy with IgM monoclonal gammopathy can be a disabling disorder necessitating treatment. METHODS: In a prospective open label trial, 17 patients with disabling IgM MGUS polyneuropathy were treated with rituximab, a chimeric anti-CD-20 monoclonal antibody. RESULTS: Rituximab induced an improvement of >or=1 point on the Overall Disability Sum Score in 2/17 patients, an improvement of >or=5% of the distal MRC sum score in 4/17 and the sensory sum score in 9/17 patients. Bone marrow investigations showed CD 20 B cell depletion in all patients. There were no serious adverse events. Compared with treatment with intermittent cyclophosphamide with prednisone or treatment with fludarabine, it shows a comparable response percentages but fewer side effects. The presence of anti-MAG and a disease duration shorter than 10 years may predict treatment response. CONCLUSION: Rituximab is a candidate for treatment of IgM MGUS polyneuropathy and should be further investigated in a double-blind randomised trial.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunoglobulin M/immunology , Immunologic Factors/therapeutic use , Paraproteinemias/drug therapy , Paraproteinemias/immunology , Age of Onset , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Murine-Derived , Antigens, CD20/metabolism , B-Lymphocytes/immunology , Bone Marrow Cells/physiology , Cyclophosphamide/therapeutic use , Disability Evaluation , Female , Humans , Immunologic Factors/adverse effects , Immunosuppressive Agents/therapeutic use , Lymphocyte Count , Male , Middle Aged , Muscle Strength/physiology , Neural Conduction/physiology , Prednisone/therapeutic use , Prospective Studies , Rituximab , Sensation/physiology , Treatment Outcome , Vidarabine/analogs & derivatives , Vidarabine/therapeutic useABSTRACT
OBJECTIVE: To describe the results of allogeneic stem cell transplantation after non-myeloblative conditioning in high-risk patients with a haematological malignancy. DESIGN: Prospective and descriptive. METHOD: In the Utrecht University Medical Centre 21 patients in an advanced stage of various haematological malignancies were treated with allogeneic stem cell transplantation following non-myeloablative conditioning. The patients were either younger than 55 but unsuitable for standard allogeneic stem cell transplantation because of co-existing disease, or between the ages of 55 and 70, and they had to have either a HLA-identical donor relative or a donor in which there was only one mismatched antigen. They were treated with a combination of fludarabine and a low dose of total body irradiation, followed by the administration of an unmanipulated stem cell transplantated. RESULTS: Engraftment of the stem cells was rapid in all patients but one, and 9 patients already showed complete donor cell chimerism 4 weeks after the infusion of stem cells. A total of 12 patients ultimately became completely donor chimeric, one of whom had received donor leucocytes; 7 patients were still mixed chimeric, with > 80% donor cells. 13 patients developed acute 'graft-versus-host disease' (GVHD), but in 10 of these it was mild and transitory. After a median follow-up of 9 months, 5 patients (24%) had died, 4 as a result of disease progression and one from a cause related to the transplantation. CONCLUSION: Allogeneic stem cell transplantation following non-myelaoblative conditioning is a convenient mode of therapy with a low mortality related to the transplantation. It is particularly suitable for the treatment of older patients at high risk with regard to their disease.
