Autoimmune Cytopenias in Chronic Lymphocytic Leukemia, Facts and Myths

Abstract

CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA) is the most common autoimmune complication of CLL and has been reported in 10–25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT) is positive in 7–14% of CLL patients but AIHA may also occur in DAT negative patients.Autoimmune thrombocytopenia (AIT) is the second most common complication of CLL and has been reported in 2–3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN) and pure red cell aplasia (PRCA) are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL). Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD), paraneoplastic pemphigus (PNP), acquired angioedema, and anti-myelin associated globulin are rare.Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg), cyclosporine, and rituximab are used in complex, steroid refractory cases. Monotherapy with purine analogues and alkylating agents should be avoided as they may increase CLL associated autoimmune complications.

Autoimmune cytopenias in chronic lymphocytic leukemia

“…As mentioned before, platelet antibody assays aimed at measuring the autoantibodies bound to platelets have limited diagnostic utility mainly because of very low specificity, but can be useful in selected complicated cases. Finally it should be noted that about 30% of ITP cases also have simultaneous AIHA (Evans Syndrome) .…”

An update on antibody drug conjugates

“…This mechanism of ADCs is in contrast to monoclonal antibodies which act by antibody -dependent cell-mediated cytotoxicity mechanism. 1 ADCs in Hematological malignancies: One of the first ADC s approved for oncologic indications was Brentuximab Vedotin (BV) in Hodgkin's lymphoma (HL).…”

Non-Hypersplenism Causes of Peripheral Cytopenias in Patients with Cirrhotic Portal Hypertension: A Review

“…The former is more common [26] and includes cytopenias caused by post-autoimmune hepatitis cirrhosis and autoimmune lymphoproliferative syndrome [29,30]. The latter, also known as basic immune thrombocytopenia, is an acquired immune disease common in chronic lymphocytic leukemia [31,32], variable immunodeficiency disease [33,34], and hemophagocytic syndrome [35], presenting with abnormal bleeding due to decreased platelet counts. Thrombocytopenia due to immunodeficiency occurs in cases of increased antibody-mediated platelet destruction coupled with decompensation due to bone marrow defect [36].…”