Autoimmune conditions and chronic infections in chronic lymphocytic leukemia patients at diagnosis are associated with unmutated IgVH genes

Vanura, Katrina; Le, Trang; Esterbauer, Harald; Späth, Florentin; Porpaczy, Edit; Shehata, Medhat; Eigenberger, Karin; Hauswirth, Alexander W.; Skrabs, Cathrin; Krömer, Elisabeth; Schwarzinger, Ilse; Streubel, Berthold; Steininger, Christoph; Fonatsch, Christa; Stilgenbauer, Stephan; Wagner, Oswald; Gaiger, Alexander; Jäger, Ulrich

doi:10.3324/haematol.12955

Cited by 23 publications

(21 citation statements)

References 23 publications

(20 reference statements)

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“…Nearly all of our patients had already received several lines of treatment either for progressive CLL, autoimmune cytopenia or both. As previously reported in CLL patients developing AIHA [13,14], they exhibited in most cases adverse prognostic factors, namely unmutated IGHV and 11q deletion. BR therapy led to a prolonged control of AIHA in 80% of cases, although the complete response rate for AIHA was rather low.…”

Section: Discussionsupporting

confidence: 71%

Bendamustine and rituximab combination in the management of chronic lymphocytic leukemia‐associated autoimmune hemolytic anemia: A multicentric retrospective study of the French CLL intergroup (GCFLLC/MW and GOELAMS)

et al. 2015

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We report our experience on bendamustine and rituximab (BR) combination in 26 patients with chronic lymphocytic leukemia (CLL) complicated by autoimmune hemolytic anemia (AIHA). At the time of BR initiation, 88% of the patients had already been treated for AIHA and CLL was progressive regardless of AIHA in all patients but one. Overall response rates were 81% for AIHA and 77% for CLL. Median time to next treatment was 28.3 months and 26.2 months for AIHA and CLL, respectively. BR therapy may represent a good and safe therapeutic option in this setting where adequate control of CLL seems important for longterm AIHA response.

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Section: Discussionsupporting

confidence: 71%

Bendamustine and rituximab combination in the management of chronic lymphocytic leukemia‐associated autoimmune hemolytic anemia: A multicentric retrospective study of the French CLL intergroup (GCFLLC/MW and GOELAMS)

et al. 2015

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“…Ͻ 12 months) correlated with the risk of developing autoimmune cytopenia. More recently, some studies have found an association between autoimmune cytopenia and unfavorable biomarkers, including unmutated IGHV genes, 7,[31][32][33] high expression of CD38 34 or ZAP-70, 7,35 and increased B2M serum levels. 28,29,32 In our series we also found a correlation between increased serum B2M levels, high ZAP-70 or CD38 expression, and autoimmune cytopenia.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance

Moreno¹,

Hodgson²,

Ferrer³

et al. 2010

Blood

123

130

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We analyzed prevalence, characteristics, clinical correlates, and prognostic significance of autoimmune cytopenia in patients with chronic lymphocytic leukemia. Seventy of 960 unselected patients (7%) had autoimmune cytopenia, of whom 19 were detected at diagnosis, 3 before diagnosis, and 48 during the course of the disease. Forty-nine patients had autoimmune hemolytic anemia, 20 had immune thrombocytopenic purpura, and 1 had both conditions. A clear association was observed between autoimmune cytopenia and poor prognostic variables (ie, high blood lymphocyte count, rapid blood lymphocyte doubling time, increased serum ␤-2 microglobulin level, and high expression of -associated protein 70 and CD38). Nevertheless, the outcome of patients with autoimmune cytopenia as a whole was not significantly different from that of patients without this complication. Furthermore, no differences were observed according to time at which cytopenia was detected (ie, at diagnosis, during course of disease). Importantly, patients with advanced (Binet stage C) disease because of an autoimmune mechanism had a significantly better survival than patients in advanced stage related to a massive bone marrow infiltration (median survivals: 7.4 years vs 3.7 years; P ‫؍‬ .02). These results emphasize the importance of determining the origin of cytopenia in patients with chronic lymphocytic leukemia for both treatment and prognostic purposes. (Blood. 2010; 116(23):4771-4776)

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“…Of note, Cuttner and colleagues analyzed HL and CLL patients with the control group. Other studies reported 39% AI among MALT lymphoma patients [11], and 16% and 11.8%, respectively, in CLL [12,21]. In all three studies, AI patients with malignant diseases were predominantly women.…”

Section: Discussionmentioning

confidence: 90%

“…In total, 574 patients with malignant lymphoma were diagnosed at the unit between 2001 and 2005. Of note, this number does not include patients with chronic lymphocytic leukemia (CLL) and MALT lymphoma since results for these entities were published elsewhere [11,12]. Of 574 patients, 94 were excluded from the analysis because of underlying immunosuppression (HIV positivity, post transplant lymphoproliferative disorder, common variable immunodeficiency) or because they were classified as primary CNS lymphomas.…”

Section: Patientsmentioning

confidence: 99%

Prevalence and clinical impact of autoimmune diseases and chronic infections in malignant lymphomas at diagnosis

et al. 2011

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There is increasing evidence for the role of chronic antigenic stimulation (CS) in the development of cancer. Clinical data, however, are rare as is the information on outcome. In this study, the occurrence of chronic infections (CI) and autoimmune diseases (AI) in patients with malignant lymphoma at diagnosis was assessed. Of 367 patients (non-Hodgkin´s lymphoma (NHL) N=297, Hodgkin´s lymphoma (HL) N=70), 9.8% (N=36) had a history of chronic antigenic stimulation (4.4% AI, 5.4% CI) at diagnosis. After a median observation time of 74.7 months, 118 patients have died. There were more male patients in this cohort.However, sex ratio among patients with chronic antigenic stimulation was skewed in favor of women (p=0.018), in particular among lymphoma patients with AI (p=0.001). NHL patients with autoimmune diseases showed a tendency to develop diffuse large B cell lymphoma (DLBCL) (8 of 12 AI+NHL patients (66.7%) vs. 100 of 266 non-CS NHL (37.6%); p=0.066).No significant difference in overall survival (OS) between CS and non-CS patients could be observed (median OS after 48 months was: CS 77.7% vs. non-CS 71.8%).In conclusion, chronic antigenic stimulation at diagnosis appears to be associated with a higher prevalence in women, in particular among patients with autoimmune disease. However, no difference in overall survival was observed. This suggests that the presence of chronic inflammatory conditions does not decisively influence the outcome of lymphoma patients.

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Autoimmune conditions and chronic infections in chronic lymphocytic leukemia patients at diagnosis are associated with unmutated IgVH genes

Cited by 23 publications

References 23 publications

Bendamustine and rituximab combination in the management of chronic lymphocytic leukemia‐associated autoimmune hemolytic anemia: A multicentric retrospective study of the French CLL intergroup (GCFLLC/MW and GOELAMS)

Bendamustine and rituximab combination in the management of chronic lymphocytic leukemia‐associated autoimmune hemolytic anemia: A multicentric retrospective study of the French CLL intergroup (GCFLLC/MW and GOELAMS)

Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance

Prevalence and clinical impact of autoimmune diseases and chronic infections in malignant lymphomas at diagnosis

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