%0 Journal Article
%T Large granular lymphocytosis with severe neutropenia following ipilimumab therapy for metastatic melanoma
%A Guoqing Wei
%A Uzoma Nwakuche
%A Gustavo Cadavid
%A Asim Ajaz
%A Karen Seiter
%A Delong Liu
%J Experimental Hematology & Oncology
%D 2012
%I BioMed Central
%R 10.1186/2162-3619-1-3
%X Cytotoxic T-lymphocyte antigen-4 (CTLA-4), a molecule present on activated T cells, is a homologue of CD28 that inhibits B7 co-stimulatory molecules expressed on mature antigen presenting cells. Ipilimumab is a fully humanized monoclonal antibody against CTLA-4 [1]. Ipilimumab is FDA approved in the United States for treatment of unresectable or metastatic melanoma [1,2]. We report the first case of large granular lymphocytosis with severe neutropenia following ipilimumab therapy.A 74 year old female presented with relapsed melanoma in the left lower extremity in Sept 2009. She was treated with temozolomide. In July 2010, she developed metastatic melanoma. She was enrolled onto a clinical trial and treated with ipilimumab on Sept 16, 2010 and October 7, 2010 at 3 mg/kg (232 mg per treatment) q3wks. Her baseline CBC was normal. At the start of the third dose, there was a significant decline in the patient's WBC count. Therefore ipilimumab was stopped. The patient was admitted on November 2, 2010 with fever, malaise and generalized weakness. She was noted to have Hgb 6.2 G/dL, WBC 1.3 กม 106 /L with no neutrophils, and platelet count of 158 กม 106 /L. The patient had a bone marrow evaluation which showed mildly hypercellular cellular marrow with marked myeloid hypoplasia/aplasia, relative erythroid hyperplasia and mild megakaryocytic atypia. Karyotype analysis demonstrated 46 XX, but FISH analysis showed a 5q31 deletion with EGR1 gene deletion in 14% of the cells. Flow cytometry study showed 46% T-cells with 20% large granular lymphocytes and 12% NK cells. A T-cell receptor gene study by Genzyme showed clonal T-cell receptor gamma gene rearrangement. These findings were consistent with myelodysplasia and large granular lymphocytosis with severe neutropenia. In addition to broad-spectrum antibiotics and G-CSF, the patient was given IVIG without significant response. The CBC on Nov 17 was WBC 0.8, Hgb 8.9, and Platelets 271. CT scans revealed bilateral loculated pleural e
%U http://www.ehoonline.org/content/1/1/3