Abstract
Chronic lymphocytic leukemia ( CLL ) is the commonest leukemia in the western world. 2% of CLL patients present with immune thrombocytopenic purpura ( ITP ). Corticosteroids, intravenous immune globulins ( IVIG ) and splenectomy have been the mainstay of treatment of ITP. Rituximab is the monoclonal antibody against CD-20 antigen expressed on the B-lymphocytes. It has established its role in the treatment of many B-cell malignancies in the last one decade. Due to its B-cell depletion capability, interests in employing rituximab in the treatment of many autoimmune diseases have grown in the last few years. Recently, many small case reports/series and a few small trials have reported the efficacy of rituximab in the treatment of refractory ITP. However, not much is known about its efficacy in the ITP associated with CLL. Here, a patient with CLL initially presenting with ITP is described.
A 67-year-old white female with a past history of hysterectomy for fibroids and hypertension presented with rectal bleeding and multiple ecchymoses. Physical examination was unremarkable except for skin eccymoses on the extremities and abdomen. Colonscopy revealed hemorrhoids only. Computerized tomograms showed no lymphadenopathy or other abnormalities. Here laboratory data were as follows; hemoglobin 5.8g/dl, WBC 29,400/mm3, platelet 13,000/mm3, lymphocyte 52%, neutrophil 45%, monocyte 2.5%. Chemistry profile was unremarkable. Her blood group was O, Rh-negative. She was initially treated at another institution with packed Red Blood Cells, prednisone 1.5mg/kg qd and daily IVIG 0.4g/kg for 5 days for presumed ITP. Platelet transfusions did not raise the platelet counts. She remained profoundly thrombocytopenic and was subsequently transferred to our hospital.
Review of the blood smear revealed anisopoikilocytosis, few tear-drop RBCs, many small-to-medium sized mature lymphocytes, occasional smudge cells, large platelets, few Pseudo-Pelgar-Huet cells but no blasts. Given moderate absolute lymphocytosis ( 15,200/mm3 ), blood film findings and profound thrombocytopenia, a working diagnosis of CLL-associated ITP was entertained. Peripheral blood flow cytometry showed lymphocytes positive for CD5, CD19, CD20 (dim ) and CD23, kappa/lambda ratio of 248:1. Bone marrow biopsy showed moderate lymphocytosis with the same immunophenotype as peripheral blood. Megakaryocytes were abundant. The diagnosis was confirmed.
She was treated with a course of high dose methylprednisone, 2 courses of IVIG 1g/kg x 2days with very transient response. Due to this, she underwent splenectomy but her platelet counts remained low. She required another 5 courses of IVIG resulting in brief responses over the next 3 weeks. She was subsequently put on po danazol 200mg bid with short-lived responses. Eventually, she received iv rituximab 375mg/m2 weekly for 4 weeks. She achieved complete remission within 1 month. Two months later, she transferred her care to another facility.
Review of the literature showed 1 case report of CLL-associated refractory ITP successfully treated with rituximab and the response duration was 6 months. Three CLL patients with refractory fludarabine-associated ITP also responded to rituximab. Of them, two achieved a platelet count over 100,000/mm3 and 1 achieved a platelet count of 72,000/mm3 within 4 weeks. Duration of responses ranged from 6 to 17 months. Those results together with our case suggest rituximab is an alternative agent for the treatment of CLL-associated ITP. Its potential in ITP associated with B-cell lymphoid malignancies should be explored further.
Incidence and outcomes of refractory immune thrombocytopenic purpura in children: a retrospective study in a single institution
