Agranulocytosis unresponsive to growth factors following rituximab in vivo purging.

the annexin V Kozak sequence (Ϫ1CϾT) increases translation efficiency and plasma levels of annexin V, and decreases the risk of myocardial infarction in young patients. Agranulocytosis unresponsive to growth factors following rituximab in vivo purging Rituximab, a chimeric monoclonal anti-CD20 antibody, has been successfully used to in vivo purge CD20 ϩ tumor cells during mobilization for high-dose therapy with autologous stem cell transplantation. 1-6 Posttransplantation neutropenia has been observed in as many as 25% of patients, although, to date, all reported patients have responded to growth-factor administration. In this report, we describe a case of agranulocytosis refractory to high-dose stem cell growth factors and ultimately responsive to cyclo-sporine following autologous stem cell transplantation for non-Hodgkin lymphoma (NHL) purged in vivo with rituximab. A 46-year-old man who presented with stage IV lymphocyte-predominant Hodgkin disease was treated with standard chemo-therapy and achieved a brief partial response. Review of the pathology resulted in modification of the diagnosis to diffuse large B-cell lymphoma, T cell and histiocyte rich. Standard CHOP chemotherapy resulted in another brief partial response. At the time of disease progression, in preparation for an autologous stem cell transplantation, the patient received and responded to 2 cycles of ifosphamide, mesna, carboplatin, and etoposide (Figure 1). He underwent successful chemomobilization therapy that included 2 doses of 375 mg/m 2 rituximab, 7 days apart. He received 3.3 ϫ 10 6 CD34 cells/kg following a myeloablative conditioning regimen. Trilineage engraftment occurred by day 9 after transplantation. Rituximab was administered on days 30 and 37 without complication. On day 77, his total white blood cell (WBC) count was 5000 mm 3 with 86% neutrophils, hemoglobin level 12.0 g/dL, platelet count 132 mm 3. On day 122, the patient had a WBC of 1000/mm 3 with 0.0% neutrophils, hemoglobin level 13.0 g/dL, platelet count 185 000 mm 3. A bone marrow biopsy performed on day 128 showed hypocellular bone marrow with little maturation of the myeloid series and no evidence of disease relapse. Dysplastic features were not observed despite a new cytogenetic abnormality, del(20)(q11.2). An extensive evaluation for an infectious etiology was negative. Autoantibodies against granulocytes were not detected. Possible offending agents were discontinued. Granulocyte colony–stimulating factor (GCSF) began followed by 2 doses of intravenous immunoglobulin and granulocyte-macrophage colony– stimulating factor (GM-CSF). Despite these maneuvers, absolute neutropenia persisted for longer than 65 days. Within 5 days of initiating therapy with cyclosporine (200 mg orally twice a day), …