Autoimmune disorders in patients with B-cell chronic lymphocytic leukemia.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7103-7103
Author(s):  
Wei Duan-Porter ◽  
Alicia D. Volkheimer ◽  
Evan D. Davis ◽  
Youwei Chen ◽  
Sallie Allgood ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Medical Center ◽  
Laboratory Data ◽  
Autoimmune Disorders ◽  
Lymphocytic Leukemia ◽  
Published Data ◽  
Autoimmune Conditions ◽  
Duke University ◽  
Cell Chronic Lymphocytic Leukemia

7103 Background: B-cell chronic lymphocytic leukemia (CLL) results from the accumulation and proliferation of malignant B cells with a predisposition for autoreactivity and autoimmune disease, particularly hematologic disorders such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). We sought to define the prevalence of autoimmune conditions and associated prognostic factors in our CLL cohort. Methods: We retrospectively reviewed the electronic medical records (EMR) of CLL patients at Duke University Medical Center (DUMC) and Durham VA Medical Center (DVAMC) for known diagnoses of autoimmune conditions, or clinical descriptions matching those disorders. Laboratory data confirming the diagnoses (e.g., Coombs test for AIHA) were verified directly in our EMR. IGVH mutation status, CD38 and ZAP-70 expression were previously determined. Results: We found 92 CLL patients with autoimmune disorders (21.4% prevalence), with higher numbers of both hematologic (58, 11.1%) and non-hematologic(42, 8.1%) conditions than previously published data [Barcellini et al. Haematologica (2006) 91:1689], although one series did show 9.7% of CLL patients with hematologic phenomena [Hamblin et al. J Clin Path (1986) 39:713-6]. CLL patients with AIHA and/or ITP had significantly shorter treatment-free survival [2.1 years (1-3.3)] and overall survival [11.9 years (9.6-15.8)] than those without [6.2 years (5.2-7.3) and 18.0 years (14.0-22.6), respectively]. 52% of CLL patients with autoimmunity had mutated IGVH (41/79 known results), 18% were CD38 positive (16/89) and 49% were ZAP-70 positive(39/80). In CLL patients without autoimmune disorders, the prevalence of mutated IGVH, and CD38 and ZAP-70 positivity were similar at 60% (219/364), 25% (99/395), and 47% (176/377), respectively. Conclusions: There is a higher prevalence of both hematologic and non-hematologic autoimmune disorders in our CLL cohort than previously reported. CLL patients with hematologic autoimmune disorders had shorter time to treatment and survival, compared to those without. There was no difference in frequency of mutated IGVH, CD38 or ZAP-70 expression between those patients with autoimmune conditions and those without.

Characteristics and Outcome of B-Cell Chronic Lymphocytic Leukemia in HCV-Positive Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4986-4986
Author(s):  
Stefano Molica ◽  
Rosanna Mirabelli ◽  
Demetrio Misuraca ◽  
Caterina Battaglia
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Absolute Lymphocyte Count ◽  
Serum Levels ◽  
Autoimmune Disorders ◽  
Lymphocytic Leukemia ◽  
Severe Infections ◽  
Hodgkin's Lymphomas ◽  
Cell Chronic Lymphocytic Leukemia

Abstract HCV-associated B-cell non-Hodgkin’s lymphomas (NHL) show distinctive clinico-pathological features such as older age, liver damage, presence of monoclonal gammopathy, increased incidence of autoimmune disorders, extranodal localizations and restricted histological subtypes. As far as B-cell chronic lymphocytic leukemia (CLL) is concerned, information dealing with either characteristics or outcome of HCV-associated CLL are limited. With this background we compared clinico-hematological features and outcome of 34 HCV-positive patients diagnosed at our institution as having immunologically typical B-cell CLL (i.e., CD5+/CD23+/CD79b-/SmIg dim) with 161 unselected CLL HCV-negative patients followed-up in the last 10 years. The two groups were alike with respect to main clinico-hematological features such as age (P=0.780), sex (P=0.650), absolute lymphocyte count (P=0.788), platelet count (P=0.362), haemoglobin level (P=0.704), β2-microglobulin (P=0.192), Binet stage distribution (P=0.224) and lymphocyte doubling time (LDT)(P= 0.620). As expected either ALT or AST serum levels at the time of CLL diagnosis were significantly higher in HCV-positive patients in comparison to HCV-negative ones (P<0.0001 for both). In contrast, no difference was found in the incidence of monoclonal gammopathy between HCV-positive and HCV-negative patients (10.3% versus 7.7%; P=0.708). The same applied for autoimmune disorders which were homogeneously distributed in the two subgroups (P=0.711) and accounted, more frequently, for autoimmune emolytic anemia (AEA)(HCV-negative subgroup, 5.5%; HCV-positive subgroup, 9.0%). The proportion of severe infections registered did not reflect the HCV-status (HCV-negative subgroup, 9.6%; HCV-positive subgroup 6.4%; P= 0.510). Also second tumours were equally distributed among HCV-positive and HCV-negative subgroups (10% versus 6.8%; P=0.655). Survival curves projected at 10 years did not show any statistical in terms overall survival (Hazard Risk, 0.690; 95% CI: 0.216–1.304; P=0.167). Finally, the short term hepatic toxicity of chemotherapy did not increase among HCV-positive patients (P=0.671). In conclusion, HCV-positive patients with B-cell CLL do not differ from other patients both for presentation and clinical outcome. The need to activate specific protocols of antiviral therapy appears less urgent in comparison to NHL, however, younger CLL patients HCV-positive who are eligible for therapies at higher immunosuppressive potential (i.e., chemo-immunotherapy) should be taken in special consideration.

Fludarabine and Alemtuzumab Versus Fludarabine and Rituximab in the Treatment of Relapsed B-Cell Chronic Lymphocytic Leukemia: Results from a Phase II Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5046-5046 ◽  
Author(s):  
John Gribben ◽  
Katherine Stephans ◽  
Blossom Marshal
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Adverse Events ◽  
B Cell ◽  
Phase Ii ◽  
Alkylating Agents ◽  
Single Agent ◽  
Response Rates ◽  
Lymphocytic Leukemia ◽  
Published Data ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Although single-agent fludarabine is associated with high response rates (60%–80%) in patients with previously untreated B-cell chronic lymphocytic leukemia (B-CLL), this therapy is not curative and patients will relapse from persistence of minimal residual disease. Response rates to subsequent lines of therapy drop dramatically, as does survival. Antibodies including alemtuzumab and rituximab act in synergy with fludarabine and improve responses in salvage CLL therapy. In an effort to identify an effective chemoimmunotherapy regimen for patients with relapsed CLL, a phase II, multicenter, open-label, randomized trial was initiated. B-CLL patients who had failed prior therapy were randomized to treatment with either fludarabine combined with alemtuzumab or fludarabine combined with rituximab. Four patients randomized to the cohort received fludarabine 25 mg/m2 IV and alemtuzumab 30 mg SC, on Days 1–5. Eight patients received fludarabine 25 mg/m2 IV on Days 1–5, and rituximab 375 mg/m2 IV on Days 1 and 4 of the first cycle, followed by fludarabine 25 mg/m2 IV on Days 1–5, and rituximab 375 mg/m2 IV on Day 1 in subsequent cycles. Patients were assessed monthly for response while on therapy, and interim restaging occurred at cycle 4. Those who achieved a CR received no further therapy, whereas those who achieved a PR or SD received 2 additional cycles. 12 patients (7 male and 5 female) participated in this trial and the median age was 67 years. Nine patients had Rai III/IV (2 patients in alemtuzumab arm and 7 patients in rituximab arm). All patients had failed 1 course of therapy; 9 had failed treatment with a fludarabine-based regimen, and 3 had failed treatment with alkylating agents. In the alemtuzumab arm, 2 patients developed a CMV reactivation, one of whom developed CMV viremia, which was successfully treated with gancyclovir. Of the 8 patients in the rituximab plus fludarabine arm, 6 withdrew due to adverse events and 2 patients died while on study. In the alemtuzumab plus fludarabine arm, 1 person withdrew due to adverse events and 1 patient died after the trial was closed. Overall, 3 of 4 patients in the alemtuzumab arm responded (2 complete response [CR], 1 partial response [PR]), and 3 of 7 patients in the rituximab arm (1 CR, 2 PR). Recently published data has prompted a shift in CLL therapy. Increased numbers of patients are receiving chemoimmunotherapy combinations earlier in treatment. An increased use of FR and FCR in the first-line setting made further recruitment difficult. The potential of randomizing patients to the FR arm of the study prompted low accrual and the subsequent closing of the study.

Abnormal Intracellular Level of Bax in CD3 + Cells from Untreated B-Cell Chronic Lymphocytic Leukemia Patients

2006 ◽  
Vol 12 (4) ◽  
pp. 187-192
Author(s):  
F. Scamardella ◽  
M. Maconi ◽  
L. Albertazzi ◽  
B. Gamberi ◽  
L. Gugliotta ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Intracellular Level ◽  
Cell Chronic Lymphocytic Leukemia

Cutaneous leukocytoclastic vasculitis in B-cell chronic lymphocytic leukemia patients

2019 ◽  
Vol 154 (5) ◽  
Author(s):  
Alessandro Pileri ◽  
Carlotta Baraldi ◽  
Alessandro Broccoli ◽  
Roberto Maglie ◽  
Annalisa Patrizi ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Leukocytoclastic Vasculitis ◽  
Lymphocytic Leukemia ◽  
Cell Chronic Lymphocytic Leukemia

scholarly journals Relation of Gene Expression Phenotype to Immunoglobulin Mutation Genotype in B Cell Chronic Lymphocytic Leukemia

2001 ◽  
Vol 194 (11) ◽  
pp. 1639-1648 ◽  
Author(s):  
Andreas Rosenwald ◽  
Ash A. Alizadeh ◽  
George Widhopf ◽  
Richard Simon ◽  
R. Eric Davis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Germ Line ◽  
Gene Expression Signature ◽  
Lymphocytic Leukemia ◽  
Common Mechanism ◽  
Human Leukemia ◽  
Mutational Status ◽  
Cell Chronic Lymphocytic Leukemia

The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression “signature,” irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease.

scholarly journals A 58‐year‐old man with B‐cell chronic lymphocytic leukemia and multiple strokes

2021 ◽  
Author(s):  
Francesca Magrinelli ◽  
Sara Mariotto ◽  
Gianpaolo Nadali ◽  
Giuseppe Todeschini ◽  
Massimiliano Lanzafame ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Cell Chronic Lymphocytic Leukemia
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