ALBERT

Description: Abstract 3888 Chronic lymphocytic leukemia (CLL) is a heterogeneous leukemia with a very variable outcome. The occurrence of a second malignancy (SM) or of a disease transformation (DT) may complicate the course of the disease. An aggressive diffuse large B-cell lymphoma (DLBCL) and, less frequently, a Hodgkin's lymphoma (HL) are the most commonly observed forms of DT, defined as Richter's syndrome (RS). Since the presence of enlarged “bulky nodes”, as well as the observation of extra-nodal lesions, can lead both to the suspicion of a CLL progression and to the possibility of a DT or of a SM, a biopsy of the involved tissue is the only appropriate approach for a correct diagnosis. Positron emission tomography/computed tomography (PET/CT) is currently used for the initial staging and restaging of HL and DLBCL, as well as for the identification of other malignancies. In a previous report by Bruzzi et al. (JNM, 2006), PET/CT showed a high predictive value in demonstrating or excluding DT. The same finding has been observed in single case reports, where in patients with CLL a high 18F-FDG uptake was associated with the presence of a DLBCL. With the aim of discriminating the presence of a DT or a SM malignancy, between June 2008 and June 2012, a PET/CT exam followed by the biopsy of the involved tissue was performed in CLL patients from 4 Italian centers. Patients included in this study showed disease progression requiring treatment according to the 2008 revised IWCLL criteria and clinical signs suggestive of the presence of a more aggressive disease, such as rapidly enlarging or bulky lymph nodes (diameter ≥5 cm) and/or extra-nodal lesions associated with at least one additional sign including B systemic symptoms, increased serum lactate dehydrogenase (LDH), increased β2 microglobulin (B2M). The 18F-FDG uptake was correlated with the histologic findings and, for the purpose of this study, a maximum standardized uptake value (SUVmax) ≥5 was considered highly suggestive of a more aggressive disease. Data on 64 CLL patients (median age, 66 years, range, 35–85) were retrospectively analyzed. At the time of PET/CT, the median follow-up from CLL diagnosis was 73 months (range, 3– 227 months) and a Binet C stage was observed in 16 cases (25%). Twenty-three (36%) patients were treatment-naïve and 41 (64%) had been previously treated (median number of prior treatments, 2; range, 1–4), including 14 (22%) refractory cases. Systemic symptoms were recorded in 25% of cases, LDH was increased in 41% and B2M in 72%. The majority of patients (61%) were IGVH unmutated, 45% CD38 positive and 56% ZAP-70 positive. Bulky lymph nodes (diameter ≥5 cm) and/or marked splenomegaly (longitudinal diameter ≥17 cm) were observed in 30 cases (47%). Evidence of extra-nodal disease was recorded in 8 cases (12.5%): thyroid, 2 cases; uterine fundus, 1; gastric,1; bone, 1; nasopharynx, 1; skin infiltrates, 2. The biopsy confirmed a SLL/CLL diagnosis in 44 cases, a DT in 15 (DLBCL, 10; HL, 5) and SM in 5 (thyroid cancer + SLL/CLL, 2 cases; lymph node metastasis of carcynoid + SLL/CLL, 1; lymph-node metastasis of a squamous cancer, 1; lejomioma of the uterine fundus,1). Sites of abnormal 18F-FDG uptake having a SUVmax ≥5 were recorded in a total number of 30 cases, in 13/44 cases (30%) with a SLL/CLL histology, in 13/15 with DT (87%), including 9/10 (90%) cases of DLBCL and 4/5 (80%) HL. An abnormal uptake was recorded also in 4/5 patients with SM. Based on these results, for the diagnosis of a DT or SM, PET/CTPET/CT showed an overall sensitivity, specificity, positive and negative predictive values of 85% 70%, 57% and 91%, respectively, while for the diagnosis of a DT (DLBCL+HL) the sensitivity, specificity, positive and negative predictive values were 87%, 65%, 43% and 94%, respectively. The cases with a SLL/CLL histology having a SUVmax ≥5 were characterized by a higher Ki-67% expression (p=0.0001) suggesting a high rate of cell turnover. Our results show that a PET/CT performed in CLL patients at the time of disease progression can detect cases with a high likelihood of DT or SM, representing therefore a very helpful imaging technique in guiding the appropriate site that should be considered for biopsy. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3192 Autoimmune hemolytic anemia (AIHA) is a rare disease, with an incidence of 1:100,000 for warm AIHA and of 1:1,000,000 for cold AIHA. AIHA can occur without any evidence of an underlying disorder (idiopathic or primary AIHA) or can be diagnosed in association with another disease (secondary AIHA), such as a malignancy, a lymphoproliferative disorder (LD), an autoimmune disorder, an infection. A successful treatment of secondary AIHA is based upon the treatment of the associated disease. In particular, the detection of a possible underlying LD is a relevant issue since a successful treatment approach for both conditions includes monoclonal antibodies that target B lymphocytes producing the anti-erythrocyte autoantibody (AeAb). With the aim of unravelling the presence of an associated disease, between January 2000 and January 2012, patients with an AIHA diagnosis defined as “primary” on clinical grounds and observed at our institution were included in this study. Patients were required to show anemia, serological evidence of an AeAb by a positive direct antiglobulin test, clinical and laboratory signs of hemolysis, no previous history and/or clinical signs of an associated malignancy, LD, autoimmune disorder, infection or a prior use of drugs commonly implicated in the pathogenesis of AIHA. Before starting treatment, a diagnostic work-out including the following examinations was carried out: autoantibody profile (anti-nucleus; anti-cardiolipin; anti-gastric parietal cells; anti-beta 2-glycoprotein-I; anti-peroxidase and anti-thyroglobulin); HBV, HCV and HIV serology; total body CT scan or chest X-ray associated with an abdomen ultrasound, bone marrow (BM) aspirate and biopsy, peripheral blood (PB) and BM immunophenotype by 4 color flow-cytometry analysis (CD19/CD5/CD3/CD20; CD23/CD10/CD19/CD20; Igκ/Igλ; CD19/CD5; CD3/CD4/CD45/CD8). Sixty-four patients were included in the study, 23 males and 41 females with a median age of 65.5 years (range: 20–83). The median Hb value was 7.9 g/dl (range: 4–11 g/dl), the median value of indirect bilirubin 2.2 mg/dl. The AeAb isotype form was an IgG in 38 cases (59%), IgM in 25 (39%; cold IgM associated with IgG, 4 cases; warm IgM, 1 case) and IgA in 1. After the initial screening, a primary AIHA diagnosis was confirmed in 38 cases (59%), while in 21 patients (33%) an underlying LD was detected, in 2 (3%) a cancer (breast, larynx), in 2 (3%) an autoimmune disorder (Hashimoto's thyroiditis, athrophic gastritis), in 1 an active HCV hepatitis. In the majority of cases (19/21, 90.5%) the diagnosis of LD was made on the basis of the BM biopsy. In all cases with BM involvement, PB flow-cytometry revealed the presence of monoclonal B lymphocytes (median number of clonal lymphocytes, 0.405×109/L) displaying most frequently a lymphoma-like phenotype (CD5−/CD20+/CD23±). As expected, the group of patients with the evidence of a LD included a significantly higher rate of cases with an IgM AeAb as compared to the group with “true” primary AIHA (67% vs 12.5%; p= .005). Taken together, the results of this study demonstrate that in 41% of patients with an AIHA defined as primary on clinical grounds, an extended diagnostic work-out allowed to identify an associated disease, most frequently a LD involving the BM associated with a clonal B population in PB. These data suggest that in patients with a diagnosis of AIHA, an extended screening including a BM biopsy and a PB immunothenotype should be considered in order to identify (or exclude) the presence of a LD and to address the appropriate treatment. Disclosures: No relevant conflicts of interest to declare.