Effective use of rituximab for acquired amegakaryocytic thrombocytopenia
Authors: Dries Deeren, Jo Van Dorpe
Journal: American Journal of Hematology (2010)

Few articles on acquired pure megakaryocytic aplasia (APMA) have been published. APMA results in severe isolated thrombocytopenia. In contrast with immune thrombocytopenic purpura bone marrow megakaryocytes are completely or almost absent. APMA has been associated with hematologic diseases such as aplastic anemia, myelodysplasia, and acute myeloid leukemia but also with other diseases such as lupus. The pathogenesis of this rare disease is uncertain. In the most recently reported cases, cyclosporine or mycophenolate mofetil (MMF) have been prescribed with success, focusing on a disturbance of cellular immunity [1-4]. However, both cellular and humoral immunity mechanisms have been proposed [1]. In the latter, antithrombopoietin antibodies have been implicated. In August 2009, an 89-year-old man was admitted to another department suffering from melena and profound thrombocytopenia of 3,000 mm−3. Gastroscopy with biopsies showed a large, bleeding adenocarcinoma of the stomach. Platelet transfusion led to an increase to 44,000 mm−3, followed by a decrease over the next 3 days. Neither corticosteroids nor immunoglobulin led to a platelet response. The patient was referred to our department where bone marrow aspiration and biopsy were performed, showing practically no megakaryocytes (Fig. 1). The few megakaryocytes that were detected were small. Cytogenetic analysis was normal. The working hypothesis was paraneoplastic APMA. Bone marrow biopsy section showing a nearly complete absence of megakaryocytes. The granulocytic and erythroid lineages are normally represented (hematoxylin and eosin stain; original magnification: ×200) [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com]. Because of his age and thrombocytopenia, surgery was postponed. We were concerned that products such as cyclosporine and MMF would promote tumor growth. The anti-CD20 antibody rituximab was considered a relatively safe option with possible efficacy through the antibody hypothesis. Four doses of 375 mg m−2 were administered at weekly intervals on September 24th, October 1st, 8th, and 15th. The evolution of the platelet count is shown in Fig. 2. Despite this response, the patient declined surgery. Six months after the last dose of rituximab, the patient was readmitted because of gastric bleeding en relapsed thrombocytopenia of 17,000 mm−3. He received palliative care. Evolution of the platelet count during and after four doses of 375 mg m−2 at weekly intervals, administered on September 24th, October 1st, 8th, and 15th. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com]. This observation is important because it demonstrates that a fast response of APMA can be achieved with rituximab. This may allow surgery and relief of the cause of APMA in at least some paraneoplastic cases. The platelet response is in line with a pathogenesis through antibodies. The risk of acceleration of tumor growth may be smaller than with cyclosporine or MMF, although this cannot be concluded from this case. Dries Deeren*, Jo Van Dorpe , * Department of Hematology, H.-Hartziekenhuis Roeselare-Menen vzw, Wilgenstraat 2, B-8800 Roeselare, Belgium, Department of Pathology, H.-Hartziekenhuis Roeselare-Menen vzw, Wilgenstraat 2, B-8800 Roeselare, Belgium.