The effect of treatment with Campath‐1H in patients with autoimmune cytopenias

Abstract

Summary.We describe 21 patients with severe and lifethreatening autoimmune cytopenias resistant to standard immunosuppression who were treated with the monoclonal antibody Campath-1H. Four patients had autoimmune neutropenia, four had autoimmune haemolytic anaemia, four had pure red cell aplasia, one had immune thrombocytopenia purpura (ITP), three had autoimmune haemolytic anaemia and ITP (Evan's syndrome), three had autoimmune pancytopenia (ITP, autoimmune neutropenia and autoimmune haemolytic anaemia), one had ITP (associated with acquired Glanzmann's disease) and autoimmune neutropenia, and one had ITP and red cell aplasia. Campath-1H was administered at a dose of 10 mg/d as an intravenous infusion for 10 d. Responses were seen in 15 patients, which were sustained in six. Relapse occurred in eight patients after Campath-1H treatment. Patients entering the study later, received cyclosporine after Campath-1H in an attempt to reduce the incidence of relapse. Three patients received a second course of Campath-1H; all responded but later relapsed. Fourteen patients are alive at a median of 12 months (range 4±61) after Campath-1H. Campath-1H represents an alternative therapeutic option for severe, refractory autoimmune cytopenias.

Red cell aplasia and autoimmune hemolytic anemia following immunosuppression with alemtuzumab, mycophenolate, and daclizumab in pancreas transplant recipients

“…22 In our patients, the antibody eluted from the red cells was a typical pan-agglutinating autoantibody. One possibility is that a single antibody was directed against both erythroid precursors and mature red cells in our patients, as has been previously reported in other rare cases.…”

Autoimmune haemolytic anaemia emerging during Campath treatment in a patient with CD5 negative chronic lymphocytic leukaemia

“…Campath has proven efficacy for the management of AIHA: of three patients with AIHA from a British series of autoimmune cytopenias without CLL two responded (though one relapsed mildly) and one died [3] and in a further patient coincidental AIHA and CLL were suppressed for 10 months when the patient succumbed to a widespread infection [4]. Our patient developed AIHA at the 8th week of Campath treatment.…”

“…Our patient developed AIHA at the 8th week of Campath treatment. Auto-antibodies may appear after Campath treatment: anti-cardiolipin antibodies (in one case associated with thrombosis) and anti-erythrocyte antibodies (without haemolysis) emerged in patients with autoimmune cytopaenia treated with Campath [3], and anti-thyroid antibodies developed in multiple sclerosis patients treated with the same agent [10]. It is possible that Campath destroys lymphocytes subsets capable of limiting autoimmunity allowing the emergence of auto-reactive clones.…”

“…Its usefulness extends to autoimmune cytopenias [3], at times developing in the course of CLL [4,5]. The CD5 negative variant of B CLL ranges in frequency between 7 % and 20 % according to series [6,7], is associated with Binet stage A and splenomegaly at diagnosis [8] and runs an aggressive clinical course [9].…”

Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody)

“…18 Alemtuzumab, a monoclonal antibody directed against the CD52 antigen, has also been reported to be effective in patients with nonCLL-related autoimmune cytopenias. [19][20][21][22] Alemtuzumab has also shown antitumour activity against B-CLL, with a response rate of 30-40% in patients with advanced B-CLL, who were previously treated with alkylating agents and had failed fludarabine therapy 9,12 This antitumor activity, in combination with its profound immunosuppressive activity, 13 merits investigation in patients with severe CLL-related AIHA as well. We have recently reported on one patient with CLL and AIHA, who had life-threatening AIHA.…”