Autoimmune Cytopenia in CLL

Abstract

Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune hemolytic anemia and immune thrombocytopenia and, less frequently, with pure red cell aplasia and immune neutropenia. The emergence of these complications is related to an intertwined and complex relationship between patient, disease, and treatment characteristics. The prognostic repercussion of autoimmune cytopenia (AIC) in patients with CLL mainly depends on its response to therapy. For patients with AIC and nonactive CLL, treatment is as in primary, uncomplicated AIC, keeping in mind that no response is an indication for CLL therapy. The success of treating active CLL-related AIC widely relies on a flexible strategy that should include initial therapy with corticosteroids and a rapid shift to effective CLL therapy in nonresponding patients. Targeted therapies (e.g., ibrutinib) that have already demonstrated to be effective in CLL-related AIC will likely offer a unique possibility of treating both AIC and CLL as a single target.

Pure red cell aplasia occurring during ibrutinib therapy for chronic lymphocytic leukemia

“…For CLL patients without a known history of pre-existing AIC, a low incidence of treatment-emergent AIC was reported during ibrutinib treatment, similar to that was observed in treatment with immunochemotherapy (1–6% vs 1–5%), both in clinical trials and real-world practice. 7–10 In the reported patient here, the PRCA appeared after ibrutinib was administered, and no other drugs were taken simultaneously, indicating ibrutinib was the most likely cause of the adverse event. Moreover, the Naranjo Algorithm Assessment score was 7 points, and the causal relationship was determined as probable (Supplemental material).…”

“…The effects of ibrutinib on the occurrence of AIC among CLL patients remain controversial. Although many clinical trials and retrospective studies showed a low incidence of treatment-emergent AIC, 7–10 there are consistent reports of acute flares of AIC occurring after ibrutinib initiation. 11,12 This report described a CLL case without prior treatment that developed PRCA after initiating ibrutinib and responded well to Cyclosporine A (CsA).…”

Autoimmune Neutropenias: Update on Clinical and Biological Features in Children and Adults

“…This new category, indeed, displayed also some distinct features such as lymphopenia with decreased B and NK cells numbers. Notably, genetic analysis showed that some of these “atypical” NP patients carried pathogenic variants that were considered causative of immunodeficiency and immune dysregulation disorders of which NP was the most evident feature 72 . These findings have clinical relevance since they suggest that pediatric diagnostic work‐up and management of NPs lasting longer than the typical time frame and appearing in late childhood and adolescence should be fairly different than the typical pAIN diagnosed in early infancy or remitting within the expected time frame.…”

“…Conversely, secondary AIN (sAIN) is mostly seen in adults, is prevalent in females, has low tendency to remit 17,70,71 and is usually associated with other autoimmune phenomena or diseases (ie, Felty syndrome, (2023) 7:1 www.hemaspherejournal.com systemic lupus erythematosus [SLE], scleroderma, Sjögren syndrome), malignancies (eg, LGL leukemias, various lymphomas), acute and chronic viral infections (eg, HIV, hepatitis, cytomegalovirus), drug reactions, and after hematopoietic stem cell transplantation (HSCT). 17,72,73 AIN in children and adolescents…”

Case report: Successful treatment of refractory immune thrombocytopenia in chronic lymphocytic leukaemia with venetoclax monotherapy

“…Corticosteroids are the mainstay for front-line management of autoimmune cytopenias in quiescent CLL ( 3 ). Adjunctive thrombopoietin (TPO) analogue and intravenous immunoglobulin (IVIG) also have a role in the context of ITP.…”