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

ABSTRACT

Introduction: 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.

KEYWORDS:

• Autoimmune cytopenias
• autoimmune hemolytic anemia
• autoimmune neutropenia
• chronic lymphocytic leukemia
• immune thrombocytopenia
• management
• pure red cell aplasia
• targeted therapies

Declaration of interest

SH Tonino has served on advisory boards for Celgene, Gilead, and Merck Sharp & Dohme. AP Kater has received research funding from Roche/Genetech, Janssen, Celgene, and AbbVie, and has served on advisory boards for AbbVie, Janssen, Roche/Genetech, and Gilead. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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This paper was not funded.