Severe Evans's syndrome secondary to interleukin-2 therapy: treatment with chimeric monoclonal anti-CD20 antibody

Abstract

Interleukin-2 (IL-2) acts by increasing the efficiency of the immune system to exert a tumoricidal effect. Although it is well known that immune stimulation with IL-2 plays a role in unmasking autoimmune phenomena such as autoimmune thyroiditis, hematological effects such as anemia and thrombocytopenia are more frequently due to toxic non-immune mechanisms. We describe a patient who developed severe Evans's syndrome [autoimmune hemolytic anemia (AHA) and immune thrombocytopenic purpura (ITP)] secondary to IL-2 therapy. ITP was refractory to multiple treatment modalities including steroids and splenectomy. ITP and AHA were initially managed with intravenous gamma globulin therapy and frequent blood transfusions, respectively. Ultimately, immunosuppressive therapy with cyclophosphamide and chimeric monoclonal anti-CD20 antibody (rituximab) were successful in inducing complete remission of Evans's syndrome.

Evans syndrome: clinical perspectives, biological insights and treatment modalities

“… 97 There are ten case reports of single patients treated with rituximab, eight adults and two children; nine of these ten patients achieved remission. 34 , 98 – 106 These studies suggest that rituximab is a good option in refractory patients, and that repeated courses are necessary to achieve long-term responses. We have previously reported the outcome of six patients with ES treated at our institution, four women and two men with an age range of 10–42 years.…”

Management of Evans syndrome

“…Evans syndrome may also develop as a secondary syndrome; a number of case reports describe Evans syndrome secondary to multicentric Castleman's disease (Marsh et al , 1990; Quinn et al , 2004), to recombinant interleukin‐2 therapy for renal carcinoma (Abdel‐Raheem et al , 2001) or following autologous (Kamezaki et al , 2004) or allogeneic (Urban et al , 2004) stem cell transplantation (SCT).…”

“…Rituximab Rituximab, a chimaeric human/mouse monoclonal antibody which targets CD20 on B lymphocytes, is increasingly used in the management of a variety of autoimmune disorders, including Evans syndrome (Abdel‐Raheem et al , 2001; Quartier et al , 2001; Seipelt et al , 2001; Galor & O'Brien, 2003; Shanafelt et al , 2003; Zecca et al , 2003; Knecht et al , 2004; Mantadakis et al , 2004; Quinn et al , 2004; Urban et al , 2004; Jubinsky & Rashid, 2005). Studies of the use of rituximab in Evans syndrome are summarised in Table III.…”

“…Single case reports of the use of rituximab in Evans syndrome As shown in Table III, of the eight patients described in the case reports (Abdel‐Raheem et al , 2001; Seipelt et al , 2001; Galor & O'Brien, 2003; Knecht et al , 2004; Mantadakis et al , 2004; Quinn et al , 2004; Urban et al , 2004; Jubinsky & Rashid, 2005), seven achieved a CR, as did the patient in Quartier's series with AIHA and ITP (Quartier et al , 2001). Of these eight patients, five were adults and three were children; the only non‐responder was a child who developed fatal secondary Evans syndrome refractory to all treatment 10 months after an unrelated donor SCT (Urban et al , 2004).…”

Rituximab therapy in a patient with autoimmune hemolytic anemia and immune thrombocytopenia associated with chronic lymphocytic leukemia

“… 1 Evans syndrome may also develop as a secondary syndrome in association with different diseases like collagen vascular diseases, lymphoproliferative disorders like CLL and multicentric Castleman disease, following autologous or allogeneic stem cell transplantation, or in response to certain chemotherapeutic or biological agents like interleukin-2 therapy. 2 – 8 The combination of AIHA and ITP in association with other disorders including CLL has been labeled as “secondary Evans syndrome” by various authors and investigators and is well documented in the literature. 2 – 4 …”