Autoimmune cytopenias in chronic lymphocytic leukemia: a concise review and treatment recommendations

Abstract

Chronic lymphocytic leukemia (CLL) is frequently complicated by cytopenias, either due to bone marrow infiltration or autoimmunity, resulting in autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia (PRCA), or autoimmune neutropenia (AIN). Morbidity due to autoimmune cytopenias (AIC) can be substantial; in addition, infection risk increases and pre-existing infections might deteriorate due to immunosuppressive medication. In the aging population, CLL occurs more frequently and AIC related to CLL represent a growing clinical challenge. Areas covered: This review summarizes current knowledge on pathophysiological mechanisms involved in AIC development and their prognostic significance. It provides diagnostic criteria and a treatment guideline for daily clinical practice, which includes the role of novel targeted agents. Expert commentary: The pathophysiology of AIC involves loss of self-tolerance, antigen presentation by malignant CLL cells, and autoantibody production through aberrant T- and B-cell function. The value of detecting autoantibodies via the direct antiglobulin test (DAT) is disputable, since a positive test does not imply overt hemolysis. Importantly, AIC should be distinguished from infiltrative cytopenias, because of prognostic and therapeutic consequences. Compared to chemotherapy, triggering AIC by targeted therapies is less common and, hence, these agents may be valuable as treatment for CLL-related immune cytopenias.

Autoimmune haemolytic anaemia and a marked rise in the lymphocyte count associated with COVID‐19 in a patient with treatment‐naïve chronic lymphocytic leukaemia: a case report

“…In addition, molecular mimicry between the red cell membrane protein ankyrin 1 and the viral S protein has been implicated as another mechanism for AIHA with COVID‐19 12 . AIHA in CLL occurs more in patients with unfavourable cytogenetics, and is mainly due to IgG antibodies with specificity against rhesus (Rh) D and erythrocyte protein band 3 (B3 protein) 13,14 . In our case, the patient did not have unfavourable cytogenetics, developed AIHA at a time‐point coinciding with the cytokine storm, the direct anti‐globulin test was positive for C3d, highlighting specificity of the autoantibody to the Ii and/or Pr antigens, 15 and the haemolysis completely resolved after recovery from COVID‐19.…”

Autoimmune cytopenias in chronic lymphocytic leukemia

“…The patients of chronic lymphocytic leukemia can present with autoimmune cytopenias 10. Pathophysiological mechanisms involved in the development of autoimmune cytopenias in chronic lymphocytic leukemia include loss of self-tolerance and aberrant T- and B-cell function, resulting in auto antigen presentation by malignant CLL cells, antibody production by normal B cells and reduced immunity through loss of regulatory T-cells 11…”

Autoimmune haemolytic anaemia in pancreatic adenocarcinoma: a potential paraneoplastic presentation

“…Cancer-associated haematological manifestations include AIHA, anti-FVIII antibodies, antiphospholipid antibodies and autoimmune thrombocytopenia among others 6 7. AIHA is typically observed in lymphoproliferative disorders 2 8. AIHA reports in solid tumours, except for ovarian dermoid cyst, are few and this holds especially true for pancreatic cancer 3 9…”