Alemtuzumab-Induced Red Cell Aplasia And Other Immune Cytopenias: Not So €˜Pure’

Abstract

We report on the presentation and outcome of a 28-year-old female who developed red cell aplasia following alemtuzumab therapy for relapsing remitting multiple sclerosis. The patient also developed synchronous immune thrombocytopenia and immune neutropenia, but not aplastic anemia. This patient received high dose steroids, intravenous immunoglobulin (iv.Ig), rituximab, red cell transfusions, vincristine, G-CSF, cyclosporin and mycophenolate to treat the combination of cytopenias over a period of 6 months with subsequent improvement in bone marrow function. While alemtuzumab has several recognized autoimmune complications, little is known about the potential hematological side effects. The combination of red cell aplasia, immune thrombocytic purpura and autoimmune neutropenia has not previously been described in the literature following alemtuzumab immunotherapy and highlights the importance of monthly blood monitoring post alemtuzumab administration.

Disease-modifying therapies and hematological disorders: a systematic review of case reports and case series

“…Sixteen case reports ( 21 , 24 , 27 , 31 , 33 , 35 , 40 – 45 , 64 , 67 , 69 , 74 ) and two case series ( 48 , 77 ) described the occurrence of hematological disorders after alemtuzumab treatment. Of these studies, 5 concerned the occurrence of early-onset toxicities ( 40 , 42 , 43 , 48 , 67 ), including severe cases of leukopenia, neutropenia, lymphopenia and thrombocytopenia that occurred in four female and one male patients, aged <58 years, with a medication history that included at least IFN and/or natalizumab for all of them.…”

“…Apart from one case that resulted in patient’s death ( 43 ), the remaining ones described the occurrence of hematological toxicities resulted in a full recovery. Alemtuzumab-induced late-onset hematological disorders were instead described in the remaining case reports and series ( 24 , 27 , 31 , 33 , 35 , 41 , 44 , 45 , 64 , 69 , 77 ). These events occurred in 8 male and 4 female patients [in one case ( 35 ) the sex was not reported].…”

Immune- and Non-Immune-Mediated Adverse Effects of Monoclonal Antibody Therapy: A Survey of 110 Approved Antibodies

“…There are a number of reports of mAb-induced cytopenias suggesting an underlying immune mechanism [19], but because of the lack of proper investigations, there are few convincing reports of the involvement of mAbs in type II hypersensitivity responses (Box 1). Thrombocytopenia after abciximab treatment [24,25] and cases of alemtuzumab-induced immune thrombocytopenia [26,27], neutropenia [27], autoimmune hemolytic anemia [28,29], and pure red cell aplasia [27] provide perhaps the best examples of immune-mediated true hypersensitivity responses. Apart from abciximab and alemtuzumab, rituximab has been implicated in thrombocytopenia [30], anemia [30], severe autoimmune hemolytic anemia [31], and early-onset and late-onset forms of neutropenia [30,32,33].…”

Data_Sheet_1.docx

“…Apart from one case that resulted in patient's death (43), the remaining ones described the occurrence of hematological toxicities resulted in a full recovery. Alemtuzumabinduced late-onset hematological disorders were instead described in the remaining case reports and series (24,27,31,33,35,41,44,45,64,69,77). These events occurred in 8 male and 4 female patients [in one case (35) the sex was not reported].…”