Prognostic Implications of Autoimmune Complications of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Other Chronic B Cell Lymphoproliferative Disorders (CLPD).
Authors: Giordano Karin F. , Wei Ding , Susan Slager L. , Susan Schwager M. , Timothy Call , Tait Shanafelt , Robert Phyliky L. , Nancy Bone D. , Neil Kay E. , Clive Zent S. 
Published: April 2020

Abstract
CLL/SLL and other CLPD are associated with an increased risk of autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), pure red blood cell aplasia (PRBCA), and autoimmune agranulocytosis (AIAG). CLL patients with AIHA and ITP have advanced stage disease according to the Rai and Binet clinical classifications, implying a poor prognosis. However, previous community based studies suggest that patients with CLL and immune cytopenias could have a similar prognosis to other patients with CLL. To further define the prognostic significance of autoimmune cytopenia, we studied a cohort of patients seen at the Mayo Clinic Rochester (MCR).
Methods The MCR Division of Hematology Chronic Lymphoproliferative Disease Database was used to identify patients with CLPD and autoimmune complications (AID) over a 10 year period (1 January 1995 to 30 December 2004). The clinical records of all patients with AID were thoroughly reviewed and collated with additional biological data.
Results Forty-one (6%) of 665 patients with CLPD had AID. Of the patients with CLPD and AID, 21 (51%) had AIHA, 19 (46%) had ITP, 8 (20%) had PRBCA and 2 (5%) had AIAG. 17% of patients had 2 or more AID diagnoses. In 4 patients (10%) the diagnosis of AID preceded the diagnosis of CLPD, and in 7 patients (17%) the diagnoses were made concurrently. In the 32 patients with CLL, the median lymphocyte count at diagnosis was 24.8 x 109/L (5.18 – 121.8). Of 27 CLL patients who had interphase FISH analysis performed, 12 (44%) had abnormalities associated with poor prognosis CLL (17p13–11% 11q22–22%, 12+ 11%), and 15 (56%) had results associated with a more favorable prognosis (no detectable abnormalities or 13q14 deletion as the sole abnormality). CD38 was positive (&gt; 30% of cells) in 38% of 21 tested patients. 39 patients required treatment for their AID. Treatment included corticosteroids (90%), splenectomy (31%), chemotherapy (31%), and rituximab (46%). Response rates following the first treatment for AID were: AIHA 53% complete response (CR) and 26% partial response (PR); ITP 56% CR and 22% PR; PRBCA 38% CR and 38% PR; AIAG no responses. Of the 41 patients seen over the 10 year period, there were 4 deaths (2 from CLPD).
Conclusions This study of a large cohort of community and referred patients showed a prevalence of AID similar to that reported in community based studies. We found an equivalent prevalence of AIHA and ITP as well as a substantial number of patients with 2 or more AID complications. This could be due in part to detailed workup of all cytopenias. In addition, 27% of patients did not have a prior diagnosis of a B cell malignancy when presenting with AID. The measured biological risk factors (FISH anomalies and CD38) suggest that CLL patients with AID do not have a higher percentage of high risk CLL. The majority of patients responded well to AID treatment. Mortality appears to be lower than CLL patients with non-autoimmune cytopenia. These preliminary data suggest that AID is a common and often presenting complication of CLL/SLL and other CLPD. Early diagnosis and management of AID could lead to improved outcomes.