Chronic Lymphocytic Leukemia Associated with Autoimmune Hemolytic Anemia Is Characterized by a Distinctive miRNA Signature,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3897-3897
Author(s):  
Gerardo Ferrer ◽  
Alfons Navarro ◽  
Kate E Hodgson ◽  
Dolors Colomer ◽  
Marta Aymerich ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Mirna Expression ◽  
Autoimmune Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Detection System ◽  
Clinical Stage ◽  
Lymphocytic Leukemia ◽  
Unsupervised Hierarchical Cluster ◽  
Mirna Signature

Abstract Abstract 3897 Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune hemolytic anemia (AIHA). However, the mechanisms governing the association between CLL and AIHA are poorly understood. MicroRNAs (miRNAs) are small 18–22 nucleotide long RNA molecules that regulate gene expression and play a key role in several biological processes. Importantly, deregulated miRNA expression has been implicated both in CLL and autoimmunity. This led us to speculate that patients with CLL who develop AIHA might have a different miRNA expression pattern as compared to those in whom this complication is not observed. We report here the first results of this study. We have evaluated the miRNA expression in purified CLL cells (CD19+, CD5+) from 14 patients who developed AIHA over the course of their disease and 19 sex-, age-, and clinical stage-matched controls who, after a comparable follow up time, did not develop this complication. The expression of 377 mature miRNAs was analyzed using TaqMan Human MicroRNA Arrays A v2.0 (Applied Biosystems) in an ABI 7900 HT sequence detection system. miRNA expression data was analyzed by the 2–ΔΔCt method, using RNU48 as endogenous control. Statistical analyses were performed with TiGR MultiExperiment Viewer, BRB-ArrayTools and R software. The unsupervised hierarchical cluster analysis identified two groups (CLL AIHA+ and CLL AIHA-). The supervised analysis revealed 7 miRNAs that were down-regulated in CLL AIHA+ patients compared to CLL AIHA- patients: miR-19a, miR-20a, miR-29c, miR-146b-5p, miR-324-3p, miR-340, miR-660. Interestingly, miR-146, which has previously been related to autoimmunity, regulates IL-1 receptor-associated kinase 1 and TNF receptor-associated factor 6, two key adapter molecules downstream of Toll-like and cytokine receptors. The prediction analysis of microarrays (PAM) was used to determine a set of miRNAs able to classify the samples into CLL AIHA+ and CLL AIHA-. We obtained a 122-miRNA model that classified CLL AIHA+ patients with a sensitivity of 69.4% and specificity of 68.4%. This model correctly classified 67% of the analyzed samples. In summary, CLL AIHA+ samples were characterized by a distinctive signature of 7 down-regulated miRNAs, one of which (miR-146) has previously been related to autoimmunity. Moreover, we identified 122 miRNAs that are able to predict AIHA in CLL patients. This is the first study establishing a relationship with CLL associated with AIHA and a distinctive miRNA signature, which should be useful for further studies aimed at unfolding the biologic complexity of AIHA in CLL. Disclosures: No relevant conflicts of interest to declare.

B-Cell Receptor Configuration and Adverse Cytogenetics Are Associated with Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1780-1780
Author(s):  
Francesco Maura ◽  
Carlo Visco ◽  
Erika Falisi ◽  
Reda Gianluigi ◽  
Sonia Fabris ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Germ Line ◽  
Conflicts Of Interest ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Lymphocytic Leukemia

Abstract Abstract 1780 Background: Biological features related to the development of autoimmune hemolytic anemia (AHIA) in patients with chronic lymphocytic leukemia (CLL) are crucial insights in the understanding of the pathogenesis of autoimmune phenomena in the course of the disease. Design and Methods: We retrospectively analyzed 585 CLL patients with available immunoglobulin heavy-chain variable (IGHV) gene status and B-cell receptor (BCR) configuration (HCDR3). Of them, 73 developed AIHA. The clinical characteristics at CLL diagnosis and follow-up were available in all patients, while cytogenetic analysis at the time of diagnosis was available in 409 patients. Results: Occurrence of AIHA was significantly associated with an IGHV unmutated (UM) status (p<0.0001) and unfavorable cytogenetic lesions [del(17)(p13) and del(11)(q23)] (p<0.0001). Stereotyped HCDR3 sequences were identified in 173 of 585 patients (29.6%) and were similarly represented among patients developing AIHA (28,7%) or not (29.6%). Of the stereotyped subsets, subset #3 was associated with a significantly higher risk of AIHA occurrence than the other HCDR3 configurations (p=0.004). Restricting the analysis to UM patients, a strong association was found between AIHA and “truly” UM patients, defined as patients carrying a 100% identity with the germ line configuration. Multivariate analysis showed that “truly” UM IGHV, del(17)(p13) and del(11)(q23) were the strongest independent variables associated with risk of developing AIHA (p=0.02, p=0.0002 and p=0.01, respectively). Based on the results of the multivariate analysis, we constructed a risk score of developing AIHA during time, according to the presence of none (low risk = favorable cytogenetics and mutated (M) IGHV), one (intermediated risk = unfavorable cytogenetic or UM), or two (high risk = unfavorable cytogenetic and UM) risk factors. This scoring system allowed a significant patient risk stratification (Figure 1). Conclusions: Taken together, our data indicate that an UM IGHV status and/or unfavorable cytogenetic lesions are associated with the risk of developing secondary AIHA in CLL patients and suggest a possible role of specific stereotyped BCR subsets in a proportion of cases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Safe Start of Ibrutinib in Patients with Chronic Lymphocytic Leukemia and Uncontrolled Autoimmune Hemolytic Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5560-5560 ◽  
Author(s):  
Alejandro Garcia-Horton ◽  
Rosanne St. Bernard ◽  
Alejandro Lazo-Langner ◽  
Anargyros Xenocostas ◽  
Joy Mangel ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Conflicts Of Interest ◽  
Case Reports ◽  
Laboratory Data ◽  
Case Series ◽  
Lymphocytic Leukemia ◽  
Positive Direct

Abstract It is estimated that 4-10% of patients with chronic lymphocytic leukemia (CLL) will develop autoimmune hemolytic anemia (AIHA) over the course of their disease. Ibrutinib has proven to be effective in treatment of relapsed, refractory, 17p deleted, and treatment naïve CLL. The effect of ibrutinib on AIHA in the context of CLL has not been established since patients with active hemolysis were excluded from major trials. In this abstract, we present a case series of patients that were actively hemolyzing at the start of ibrutinib therapy and in which their AIHA achieved prolonged response. Patient characteristics and laboratory data are shown in Table. Five patients (3 women, 2 men), median age 61 years (range 57 to 78), with CLL and active, uncontrolled AIHA at the time of ibrutinib initiation were identified. Uncontrolled AIHA was defined as anemia with evidence of hemolysis (at least two of the following: increased reticulocyte count, elevated lactate dehydrogenase, elevated indirect bilirubin, and reduced haptoglobin and a positive direct antiglobulin test (DAT)). Patients had a median hemoglobin of 70 g/L (range 69-96) prior to start of ibrutinib and 3 of them required transfusion support for symptomatic anemia. All patients were receiving prednisone for management of AIHA at the time of ibrutinib initiation and had been on it for a median of 10 days (range 9 - 25) without AIHA resolution. 1 patient received intravenous immunoglobulin concurrently. All patients had received at least one line of therapy for CLL in the past and 3 had experienced previous AIHA responsive to steroids. AIHA in 2 patients was related to previous fludarabine exposure but had responded to a prednisone tapering schedule and were off steroids by the time of the new AIHA flare. Median hemoglobin of 130 g/L (range 113-149) was reached at time of AIHA response. All 5 patients tolerated 420mg oral daily of ibrutinib therapy and AIHA was controlled in a median of 6.5 weeks (range 6-10). Discontinuation of steroids was achieved in all patients at a median of 10 weeks (range 6-17) without evidence of further hemolysis. All patients except one are receiving ongoing follow up and have been followed up for a median of 130 weeks (range 15-150) since ibrutinib start. Patients have not shown evidence of AIHA relapse and continue off AIHA treatment (prednisone). One patient required discontinuation of ibrutinib 6 months after starting due to neutropenia but there was no evidence of AIHA relapse in follow up. The patient has passed away from unrelated GI bleed 2 years after the initial AIHA event. This is the largest case series to our knowledge on the safe start of ibrutinib in CLL complicated by active AIHA. Hemolysis in all patients responded to a short prednisone taper with ibrutinib concurrently and obtained a sustained response at follow up without any flare ups or further AIHA treatment use. These cases suggest that it is safe to start ibrutinib during uncontrolled, active hemolysis in contrast to 2 previous case reports that suggested causal relationship between ibrutinib and onset of severe CLL-associated AIHA (Rider et al, 2015; Hodskins et al, 2014). As previously reported, AIHA occurrence or relapse once ibrutinib has been started is rare (Rogers et al, 2016). Disclosures No relevant conflicts of interest to declare.

2.36 Chronic Lymphocytic Leukemia Associated with Autoimmune Hemolytic Anemia is Characterized by a Distinctive miRNA Signature

2011 ◽  
Vol 11 ◽  
pp. S181-S182
Author(s):  
Gerardo Ferrer ◽  
Alfons Navarro ◽  
Kate Hodgson ◽  
Dolors Colomer ◽  
Marta Aymerich ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Lymphocytic Leukemia ◽  
Mirna Signature

Fatal intravascular autoimmune hemolytic anemia after fludarabine treatment for chronic lymphocytic leukemia

1996 ◽  
Vol 38 (4) ◽  
pp. 359-360 ◽  
Author(s):  
G. Tertian ◽  
J. Cartron ◽  
C. Bayle ◽  
A. Rudent ◽  
T. Lambert ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Lymphocytic Leukemia

Kaposi sarcoma following autoimmune hemolytic anemia in a patient with chronic lymphocytic leukemia

2018 ◽  
Vol 12 (1) ◽  
pp. 99-102 ◽  
Author(s):  
Utku Iltar ◽  
Vedat Aslan ◽  
Mesut Gocer ◽  
Fatma Aykac ◽  
İlknur Nizam ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Kaposi Sarcoma ◽  
Lymphocytic Leukemia

scholarly journals Autoimmune Hemolytic Anemia After Relapse of Chronic Myeloid Leukemia: A Case Report

2019 ◽  
Vol 12 ◽  
pp. 1179545X1989457
Author(s):  
Tahseen Hamamyh ◽  
Mohamed A Yassin
Keyword(s):  
Case Report ◽  
Chronic Myeloid Leukemia ◽  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Lymphocytic Leukemia ◽  
Sudden Drop ◽  
Leukemia Relapse

Autoimmune hemolytic anemia is one of the differential diagnoses for anemia in patients with lymphoproliferative neoplasia, such as chronic lymphocytic leukemia, who experience sudden drop in hemoglobin. The association between autoimmune hemolytic anemia and chronic myeloid leukemia on the contrary is unusual. Here we present a patient with a background of chronic myeloid leukemia treated previously with Tyrosine Kinase Inhibitors, then developed autoimmune hemolysis simultaneously with chronic myeloid leukemia relapse. Hemolysis was treated with steroids with good response.

Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2786-2792 ◽  
Author(s):  
Francesca R. Mauro ◽  
Robert Foa ◽  
Raffaella Cerretti ◽  
Diana Giannarelli ◽  
Serelina Coluzzi ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hemolytic Anemia ◽  
Survival Probability ◽  
Autoimmune Hemolytic Anemia ◽  
Immunosuppressive Agents ◽  
Rare Event ◽  
Lymphocytic Leukemia ◽  
Independent Effect ◽  
Complete Disappearance ◽  
Prognostic Features

Fifty-two cases of autoimmune hemolytic anemia (AHA) were observed within a series of 1203 patients (4.3%) with chronic lymphocytic leukemia (CLL) followed at a single institution. Nineteen were observed at the time of CLL diagnosis and 33 during the clinical follow-up. Ninety percent of the patients with CLL/AHA showed active CLL and 25% had been treated previously. The antierythrocyte autoantibody (AeAb) was an IgG in 87% of cases and an IgM in 13%. A lymphocyte count more than 60 × 109/L (P &lt; .00001), age above 65 years (P &lt; .01), and male gender (P &lt; .01) emerged as independent parameters that correlated significantly with an increased rate of AHA at CLL diagnosis. Patients previously treated with chlorambucil (CB) plus prednisone (PDN) and with fludarabine plus PDN showed a similar rate of AHA (1.8% and 2.5%, respectively). After steroid therapy associated with CB in case of active CLL, 70% of patients achieved the complete disappearance of the AeAb. The actuarial AHA relapse-free survival probability was 54% at 5 years and the median survival probability after AHA was 41 months. Infections represented the main cause of morbidity and mortality. IgG AHA and the occurrence of AHA at the same time of CLL diagnosis emerged as independent factors significantly correlated with a better survival probability of AHA/CLL patients. Taken together, this study indicates that in CLL, AHA is a rare event with no independent effect on survival for which steroids, associated with CB if required, and a careful management of infections may successfully control the 2 conditions. Cooperative studies are needed to better define the optimal steroid schedule and the therapeutic role of other immunosuppressive agents and splenectomy.

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