Autoimmune Complications in Chronic Lymphocytic Leukemia in the Era of Targeted Drugs

Abstract

Autoimmune phenomena are frequently observed in patients with chronic lymphocytic leukemia (CLL) and are mainly attributable to underlying dysfunctions of the immune system. Autoimmune cytopenias (AIC) affect 4–7% of patients with CLL and mainly consist of autoimmune hemolytic anemia and immune thrombocytopenia. Although less common, non-hematological autoimmune manifestations have also been reported. Treatment of CLL associated AIC should be primarily directed against the autoimmune phenomenon, and CLL specific therapy should be reserved to refractory cases or patients with additional signs of disease progression. New targeted drugs (ibrutinib, idelalisib and venetoclax) recently entered the therapeutic armamentarium of CLL, showing excellent results in terms of efficacy and became an alternative option to standard chemo-immunotherapy for the management of CLL associated AIC. However, the possible role of these drugs in inducing or exacerbating autoimmune phenomena still needs to be elucidated. In this article, we review currently available data concerning autoimmune phenomena in patients with CLL, particularly focusing on patients treated with ibrutinib, idelalisib, or venetoclax, and we discuss the possible role of these agents in the management of AIC.

Monogenic Immune Diseases Provide Insights Into the Mechanisms and Treatment of Chronic Graft-Versus-Host Disease

“…The use of antileukemic drugs that inhibit Btk signaling to promote apoptosis of malignant B cells, especially in chronic lymphocytic leukemia, theoretically may also affect B cell selection by interfering with normal BCR signaling leading to the release of autoreactive B cells. Autoimmune cytopenias have been observed in patients with chronic lymphocytic leukemia treated with ibrutinib ( 123 , 124 ).…”

Immune Dysfunctions and Immune-Based Therapeutic Interventions in Chronic Lymphocytic Leukemia

“…Another consequence of the altered humoral immunity is the occurrence of autoimmune complications. Episodes of autoimmune cytopenia are frequently observed in CLL patients and are attributable to high affinity polyclonal IgG autoantibodies which are produced by the non-leukemic B cells and target membrane antigens expressed on red blood cells, platelets, or granulocytes [as reviewed in (17,151,152)]. In addition, we previously reported that polyclonal antibodies directed to recurrent antigens expressed by tumor cells can be frequently found in the serum of CLL patients, especially those with progressive disease.…”

“…However, most of the immune surveillance dysfunctions accumulate during disease evolution, most likely constributing to the transition from MBL to CLL [as reviewed in (8,9)]. From the clinical standpoint, these immunologic dysregulations are responsible for the increased susceptibility to infections and secondary malignancies, the occurrence of autoimmune phenomena and the failure to control disease progression (10,11) [and as reviewed in (5,(12)(13)(14)(15)(16)(17)].…”

The blood cells count in leukocyte and leukocyte-poor platelet-concentrated plasma in patients with musculoskeletal disorders

“…Since the number of platelets in the whole blood of healthy adults varies in a relatively wide range of 150-450•10 6 cells/mL, this factor must be taken into account in the production of all types of platelet concentrates [16]. In addition, in some diseases, including immune thrombocytopenia and chronic leukocyte leukemia, the platelet number in the blood is reduced to 100•10 6 cells/mL and less [41,42]. When studying the correlation between the platelets count in whole blood and in the prepared concentrates, the products were divided into two groups according to the number of platelets in the processed blood.…”